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Obeagu EI, Obeagu GU. Building a Healthier Future: A Narrative Review on Early Infant Diagnosis's Role in HIV Prevention. Health Sci Rep 2025; 8:e70591. [PMID: 40124923 PMCID: PMC11925723 DOI: 10.1002/hsr2.70591] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/25/2024] [Revised: 11/21/2024] [Accepted: 02/23/2025] [Indexed: 03/25/2025] Open
Abstract
Background and Aims Early infant diagnosis (EID) is a critical intervention in the global fight against pediatric HIV, providing early identification and treatment for HIV-exposed infants. This narrative review examines the role of EID in reducing vertical transmission, improving health outcomes, and mitigating stigma in communities. The review also explores innovations, challenges, and strategies for optimizing EID programs. Methods A comprehensive literature search was conducted across databases such as PubMed, Scopus, and WHO reports to identify relevant studies, guidelines, and program evaluations. Key focus areas included diagnostic techniques, implementation strategies, and community impacts of EID programs, with an emphasis on their integration into broader HIV care frameworks. Results EID enables the early detection of HIV in infants, allowing timely initiation of antiretroviral therapy (ART), which reduces morbidity and mortality. It also indirectly prevents postnatal transmission during breastfeeding by lowering viral loads in treated infants. Innovations such as point-of-care testing and digital health tools have improved access and efficiency, particularly in resource-limited settings. EID programs have demonstrated a positive societal impact by raising awareness, reducing stigma, and fostering trust in healthcare systems. However, significant challenges persist, including logistical barriers, infrastructure limitations, and socioeconomic constraints that hinder program effectiveness. Conclusion EID is essential for addressing pediatric HIV, contributing to the elimination of vertical transmission and improving outcomes for HIV-exposed infants. To enhance its impact, stakeholders must prioritize expanding access to diagnostic tools, strengthening healthcare infrastructure, and engaging communities through education and advocacy. EID programs not only save lives but also foster societal shifts towards inclusivity and acceptance, paving the way for a healthier, HIV-free future.
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Mathur S, Smuk M, Evans C, Wedderburn CJ, Gibb DM, Penazzato M, Prendergast AJ. Estimating the impact of alternative programmatic cotrimoxazole strategies on mortality among children born to mothers with HIV: A modelling study. PLoS Med 2024; 21:e1004334. [PMID: 38377150 PMCID: PMC10914273 DOI: 10.1371/journal.pmed.1004334] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/09/2023] [Revised: 03/05/2024] [Accepted: 01/10/2024] [Indexed: 02/22/2024] Open
Abstract
BACKGROUND World Health Organization (WHO) guidelines recommend cotrimoxazole prophylaxis for children who are HIV-exposed until infection is excluded and vertical transmission risk has ended. While cotrimoxazole has benefits for children with HIV, there is no mortality benefit for children who are HIV-exposed but uninfected, prompting a review of global guidelines. Here, we model the potential impact of alternative cotrimoxazole strategies on mortality in children who are HIV-exposed. METHODS AND FINDINGS Using a deterministic compartmental model, we estimated mortality in children who are HIV-exposed from 6 weeks to 2 years of age in 4 high-burden countries: Côte d'Ivoire, Mozambique, Uganda, and Zimbabwe. Vertical transmission rates, testing rates, and antiretroviral therapy (ART) uptake were derived from UNAIDS data, trial evidence, and meta-analyses. We explored 6 programmatic strategies: maintaining current recommendations; shorter cotrimoxazole provision for 3, 6, 9, or 12 months; and starting cotrimoxazole only for children diagnosed with HIV. Modelled alternatives to the current strategy increased mortality to varying degrees; countries with high vertical transmission had the greatest mortality. Compared to current recommendations, starting cotrimoxazole only after a positive HIV test had the greatest predicted increase in mortality: Mozambique (961 excess annual deaths; excess mortality 339 per 100,000 HIV-exposed children; risk ratio (RR) 1.06), Uganda (491; 221; RR 1.04), Zimbabwe (352; 260; RR 1.05), and Côte d'Ivoire (125; 322; RR 1.06). Similar effects were observed for 3-, 6-, 9-, and 12-month strategies. Increased mortality persisted but was attenuated when modelling lower cotrimoxazole uptake, smaller mortality benefits, higher testing coverage, and lower vertical transmission rates. The study is limited by uncertain estimates of cotrimoxazole coverage in programmatic settings; an inability to model increases in mortality arising from antimicrobial resistance due to limited surveillance data in sub-Saharan Africa; and lack of a formal health economic analysis. CONCLUSIONS Changing current guidelines from universal cotrimoxazole provision for children who are HIV-exposed increased predicted mortality across the 4 modelled high-burden countries, depending on test-to-treat cascade coverage and vertical transmission rates. These findings can help inform policymaker deliberations on cotrimoxazole strategies, recognising that the risks and benefits differ across settings.
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Affiliation(s)
- Shrey Mathur
- Blizard Institute, Queen Mary University of London, London, United Kingdom
| | - Melanie Smuk
- Blizard Institute, Queen Mary University of London, London, United Kingdom
| | - Ceri Evans
- Blizard Institute, Queen Mary University of London, London, United Kingdom
- Zvitambo Institute for Maternal and Child Health Research, Harare, Zimbabwe
- Department of Clinical Infection, Microbiology and Immunology, University of Liverpool, Liverpool, United Kingdom
| | - Catherine J. Wedderburn
- Medical Research Council Clinical Trials Unit at University College London, London, United Kingdom
- Department of Paediatrics and Child Health and Neuroscience Institute, University of Cape Town, Cape Town, South Africa
| | - Diana M. Gibb
- Medical Research Council Clinical Trials Unit at University College London, London, United Kingdom
| | - Martina Penazzato
- Department of Research for Health, Science Division, World Health Organization, Geneva, Switzerland
| | - Andrew J. Prendergast
- Blizard Institute, Queen Mary University of London, London, United Kingdom
- Zvitambo Institute for Maternal and Child Health Research, Harare, Zimbabwe
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Kemper KE, Augusto O, Gloyd S, Akoku DA, Ouattara G, Perrone LA, Assoa PH, Akoua-Koffi C, Adje-Toure C, Koné A. HIV viral load testing and monitoring in Côte d'Ivoire: A survival analysis of viral load testing and suppression, and evaluation of adherence to national recommendations. PLOS GLOBAL PUBLIC HEALTH 2023; 3:e0001822. [PMID: 37708102 PMCID: PMC10501548 DOI: 10.1371/journal.pgph.0001822] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 12/11/2022] [Accepted: 07/31/2023] [Indexed: 09/16/2023]
Abstract
Routine viral load (VL) monitoring is the standard of care in Côte d'Ivoire and allows for effective treatment guidance for people living with human immunodeficiency virus (HIV) to reach viral load suppression (VLS). For VL monitoring to be effective in reducing the impact of HIV, it must be provided in accordance with national guidance. This study aimed to evaluate VL testing, VLS rates and adherence to national guidance for VL testing using data collected from three national laboratories. We collected data on VL testing between 2015-2018 from OpenELIS (OE), an open-source electronic laboratory information system. We merged data by unique patient ID for patients (0-80 years old) who received multiple VL tests to calculate time between tests. We defined VLS as HIV RNA ≤1,000 copies/mL based on Côte d'Ivoire national and WHO guidance at the time of data collection. We used the Kaplan-Meier survival estimator to estimate time between ART (antiretroviral therapy) initiation and the first VL test, time between subsequent VL tests, and to estimate the proportion of people living with HIV (PLHIV) who were virally suppressed within 12 months of ART initiation. At the first documented VL test, 79.6% of patients were virally suppressed (95% CI: 78.9-80.3). Children under 15 were the least likely to be virally suppressed (55.2%, 95% CI: 51.5-58.8). The median time from ART initiation to the first VL sample collection for testing was 7.8 months (IQR:6.2-13.4). 72.4% of patients were virally suppressed within one year of treatment initiation (95% CI:71.5-73.3). Approximately 30% of patients received a second VL test during the 4-year study period. The median time between the first and second VL tests was 24.9 months (IQR: 4.7->40). Most PLHIV received their first VL test within the recommended 12 months of ART initiation but did not receive subsequent VL monitoring tests within the recommended time frame, reducing the benefits of VL monitoring. While VLS was fairly high, children were least likely to be virally suppressed. Our findings highlight the importance of regular VL monitoring after the first VL test, especially for children.
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Affiliation(s)
- Kathryn E. Kemper
- Health Alliance International, Seattle, Washington, United States of America
- Department of Global Health, University of Washington, Seattle, Washington, United States of America
| | - Orvalho Augusto
- Health Alliance International, Seattle, Washington, United States of America
- Department of Global Health, University of Washington, Seattle, Washington, United States of America
| | - Stephen Gloyd
- Health Alliance International, Seattle, Washington, United States of America
- Department of Global Health, University of Washington, Seattle, Washington, United States of America
| | - Derick A. Akoku
- Department of Global Health, University of Washington, Seattle, Washington, United States of America
- Health Alliance International, Abidjan, Côte d’Ivoire
| | | | - Lucy A. Perrone
- Department of Global Health, University of Washington, Seattle, Washington, United States of America
- International Training and Education Center for Health, Seattle, Washington, United States of America
| | - Paul Henri Assoa
- International Training and Education Center for Health, Abidjan, Côte d’Ivoire
| | - Chantal Akoua-Koffi
- Université Alassane Ouattara, Bouaké, Côte d’Ivoire
- University Teaching Hospital Bouaké, Ministry of Health and Public Hygiene, Bouaké, Côte d’Ivoire
| | | | - Ahoua Koné
- Health Alliance International, Seattle, Washington, United States of America
- Department of Global Health, University of Washington, Seattle, Washington, United States of America
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Finocchario-Kessler S, Goggin K, Wexler C, Maloba M, Gautney B, Khamadi S, Lwembe R, Babu S, Sweat M. Incorporating the HIV Infant Tracking System into standard-of-care early infant diagnosis of HIV services in Kenya: a cost-effectiveness analysis of the HITSystem randomised trial. Lancet Glob Health 2023; 11:e1217-e1224. [PMID: 37474229 PMCID: PMC10482001 DOI: 10.1016/s2214-109x(23)00216-4] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/25/2022] [Revised: 04/11/2023] [Accepted: 04/27/2023] [Indexed: 07/22/2023]
Abstract
BACKGROUND The HITSystem efficacy trial showed significant improvements in early infant diagnosis retention, return and notification of infant test results, and earlier antiretroviral therapy (ART) initiation compared with standard-of-care early infant diagnosis services in Kenya. This study aimed to analyse data from the HITSystem trial to assess the cost-effectiveness of the intervention in Kenya. METHODS In this analysis, we extrapolated results from the HITSystem cluster randomised controlled trial to model early infant diagnosis outcomes and cost-effectiveness if the HITSystem was scaled up nationally in Kenya, compared with standard-of-care outcomes. We used a micro-costing method to collect cost data, which were analysed from a health-system perspective, reflecting the investment required to add HITSystem to existing early infant diagnosis services and infrastructure. The base model used to calculate cost-effectiveness was deterministic and calculated the progression of infants through early infant diagnosis. Differences in progression across study arms were used to establish efficacy outcomes. The number of life-years gained per infant successfully initiating ART were based on the Cost Effectiveness of Preventing AIDS Complications model in east Africa. HITSystem cost data were integrated into the model, and the incremental cost-effectiveness ratio was calculated in terms of cost per life-year gained. Sensitivity analyses were done using the deterministic model with triangular stochastic probability functions for key model parameters added. The number of life-years gained was discounted at 3% and costs were adjusted to 2021 values. FINDINGS The cost per life-year gained from the HITSystem was US$82·72. Total cost for national HITSystem coverage in Kenya was estimated to be around $2·6 million; covering 82 230 infants exposed to HIV at a cost of $31·38 per infant and a yield of 1133 infants receiving timely ART, which would result in 31 189 life-years gained. With sensitivity analyses, the cost per life-year gained varied from $40·13 to $215·05. 90% of model values across iterations ranged between $55·58 (lower 5% threshold) and $132·38 (upper 95% threshold). INTERPRETATION The HITSystem would be very cost-effective in Kenya and can optimise the return on the existing investment in the national early infant diagnosis programme. FUNDING The US National Institute of Child Health and Human Development.
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Affiliation(s)
- Sarah Finocchario-Kessler
- Department of Family Medicine and Community Health, University of Kansas Medical Center, Kansas City, KS, USA.
| | - Kathy Goggin
- Health Services and Outcomes Research, Department of Pediatrics, Children's Mercy Hospital, Kansas City, MO, USA
| | - Catherine Wexler
- Department of Family Medicine and Community Health, University of Kansas Medical Center, Kansas City, KS, USA
| | - May Maloba
- Global Health Innovations Kenya, Nairobi, Kenya
| | | | - Samoel Khamadi
- Centre for Virus Research, Kenya Medical Research Institute, Nairobi, Kenya
| | - Raphael Lwembe
- Centre for Virus Research, Kenya Medical Research Institute, Nairobi, Kenya
| | | | - Michael Sweat
- Division of Global and Community Health, Department of Psychiatry and Behavioral Sciences, Medical University of South Carolina, Charleston, SC, USA
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Riegler AN, Larsen N, Amerson-Brown MH. Point-of-Care Testing for Sexually Transmitted Infections. Clin Lab Med 2023; 43:189-207. [PMID: 37169442 DOI: 10.1016/j.cll.2023.02.006] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 05/13/2023]
Abstract
Point-of-care testing for sexually transmitted infections is essential for controlling transmission and preventing sequelae in high-risk populations. Since the World Health Organization published the ASSURED criteria, point-of-care testing has improved for use in large population screening and rapid testing that prevents loss of clinical follow-up. Recent advancements have been advantageous for low-resource areas allowing testing at a minimal cost without reliable electricity or refrigeration. Point-of-care nucleic acid detection and amplification techniques are recommended, but are often inaccessible in low-resource areas. Future advancements in point-of-care diagnostic testing should focus on improving antibody-based assays, monitoring viral loads, and detecting antimicrobial resistance.
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Affiliation(s)
- Ashleigh N Riegler
- Department of Pathology, The University of Alabama at Birmingham, Marnix E. Heersink School of Medicine, 619 East 19th Street South, WP240J, Birmingham, AL 35249-7331, USA
| | - Natalie Larsen
- Department of Pathology, The University of Alabama at Birmingham, Marnix E. Heersink School of Medicine, 619 East 19th Street South, WP240J, Birmingham, AL 35249-7331, USA
| | - Megan H Amerson-Brown
- Department of Pathology, The University of Alabama at Birmingham, Marnix E. Heersink School of Medicine, 619 East 19th Street South, WP240J, Birmingham, AL 35249-7331, USA.
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Vreeman RC, Yiannoutsos CT, Yusoff NKN, Wester CW, Edmonds A, Ofner S, Davies MA, Leroy V, Lumbiganon P, de Menezes Succi RC, Twizere C, Brown S, Bolton-Moore C, Takassi OE, Scanlon M, Martin R, Wools-Kaloustian K. Global HIV prevention, care and treatment services for children: a cross-sectional survey from the International Epidemiology Databases to Evaluate AIDS (IeDEA) consortium. BMJ Open 2023; 13:e069399. [PMID: 36914183 PMCID: PMC10016275 DOI: 10.1136/bmjopen-2022-069399] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/21/2022] [Accepted: 02/20/2023] [Indexed: 03/16/2023] Open
Abstract
OBJECTIVES To assess access children with HIV have to comprehensive HIV care services, to longitudinally evaluate the implementation and scale-up of services, and to use site services and clinical cohort data to explore whether access to these services influences retention in care. METHODS A cross-sectional standardised survey was completed in 2014-2015 by sites providing paediatric HIV care across regions of the International Epidemiology Databases to Evaluate AIDS (IeDEA) consortium. We developed a comprehensiveness score based on the WHO's nine categories of essential services to categorise sites as 'low' (0-5), 'medium', (6-7) or 'high' (8-9). When available, comprehensiveness scores were compared with scores from a 2009 survey. We used patient-level data with site services to investigate the relationship between the comprehensiveness of services and retention. RESULTS Survey data from 174 IeDEA sites in 32 countries were analysed. Of the WHO essential services, sites were most likely to offer antiretroviral therapy (ART) provision and counselling (n=173; 99%), co-trimoxazole prophylaxis (168; 97%), prevention of perinatal transmission services (167; 96%), outreach for patient engagement and follow-up (166; 95%), CD4 cell count testing (126; 88%), tuberculosis screening (151; 87%) and select immunisation services (126; 72%). Sites were less likely to offer nutrition/food support (97; 56%), viral load testing (99; 69%) and HIV counselling and testing (69; 40%). 10% of sites rated 'low', 59% 'medium' and 31% 'high' in the comprehensiveness score. The mean comprehensiveness of services score increased significantly from 5.6 in 2009 to 7.3 in 2014 (p<0.001; n=30). Patient-level analysis of lost to follow-up after ART initiation estimated the hazard was highest in sites rated 'low' and lowest in sites rated 'high'. CONCLUSION This global assessment suggests the potential care impact of scaling-up and sustaining comprehensive paediatric HIV services. Meeting recommendations for comprehensive HIV services should remain a global priority.
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Affiliation(s)
- Rachel C Vreeman
- Department of Global Health and Health System Design, Icahn School of Medicine at Mount Sinai Arnhold Institute for Global Health, New York, New York, USA
| | - Constantin T Yiannoutsos
- Department of Biostatistics and Health Data Science, Indiana University Richard M Fairbanks School of Public Health, Indianapolis, Indiana, USA
| | | | - C William Wester
- Vanderbilt Institute for Global Health, Nashville, Tennessee, USA
- Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee, USA
| | - Andrew Edmonds
- Department of Epidemiology, The University of North Carolina at Chapel Hill Gillings School of Global Public Health, Chapel Hill, North Carolina, USA
| | - Susan Ofner
- Department of Biostatistics and Health Data Science, Indiana University Richard M Fairbanks School of Public Health, Indianapolis, Indiana, USA
| | - Mary-Ann Davies
- Centre for Infectious Disease Epidemiology and Research, School of Public Health and Family Medicine, University of Cape Town, Cape Town, South Africa
| | - Valériane Leroy
- Center for Epidemiology and Research in POPulation Health (CERPOP), Inserm, Université de Toulouse, Université Paul Sabatier, Toulouse, France
| | - Pagakrong Lumbiganon
- Department of Pediatrics, Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand
| | | | | | - Steven Brown
- Department of Biostatistics and Health Data Science, Indiana University Richard M Fairbanks School of Public Health, Indianapolis, Indiana, USA
| | - Carolyn Bolton-Moore
- Center for Infectious Disease Research in Zambia, Lusaka, Zambia
- Department of Medicine, The University of Alabama at Birmingham Heersink School of Medicine, Birmingham, Alabama, USA
| | | | - Michael Scanlon
- Indiana University Center for Global Health, Indianapolis, Indiana, USA
| | - Roxanne Martin
- Department of Global Health and Health System Design, Icahn School of Medicine at Mount Sinai Arnhold Institute for Global Health, New York, New York, USA
| | - Kara Wools-Kaloustian
- Department of Medicine, Indiana University School of Medicine, Indianapolis, Indiana, USA
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Mohamed Y, Htay H, Gare J, Vallely AJB, Kelly-Hanku A, Yee WL, Agius PA, Badman SG, Pham MD, Nightingale C, Chen XS, Kombati Z, Koata A, Munnull G, Silim S, Thein W, Zaw TM, Kyaw LL, Stoové M, Crowe SM, Anderson D, Tin HH, Luchters S. The effect of the Xpert HIV-1 Qual test on early infant diagnosis of HIV in Myanmar and Papua New Guinea: a pragmatic, cluster-randomised, stepped-wedge, open-label trial. Lancet HIV 2023; 10:e220-e229. [PMID: 36871568 DOI: 10.1016/s2352-3018(23)00001-2] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/18/2022] [Revised: 12/15/2022] [Accepted: 12/19/2022] [Indexed: 03/06/2023]
Abstract
BACKGROUND Despite proven benefits for child health, coverage of early infant diagnosis of HIV remains suboptimal in many settings. We aimed to assess the effect of a point-of-care early infant diagnosis test on time-to-results communication for infants vertically exposed to HIV. METHODS This pragmatic, cluster-randomised, stepped-wedge, open-label trial assessed the effect of the Xpert HIV-1 Qual early infant diagnosis test (Cepheid) on time-to-results communication, compared with standard care laboratory-based testing of dried blood spots using PCR. Hospitals were the unit of randomisation for one-way crossover from control to intervention phase. Each site had between 1 month and 10 months of control phase before transitioning to the intervention, with a total of 33 hospital-months in the control phase and 45 hospital-months in the intervention phase. We enrolled infants vertically exposed to HIV at six public hospitals: four in Myanmar and two in Papua New Guinea. Infants had to have mothers with confirmed HIV infection, be younger than 28 days, and required HIV testing to be eligible for enrolment. Health-care facilities providing prevention of vertical transmission services were eligible for participation. The primary outcome was communication of early infant diagnosis results to the infant's caregiver by 3 months of age, assessed by intention to treat. This completed trial was registered with the Australian and New Zealand Clinical Trials Registry, 12616000734460. FINDINGS In Myanmar, recruitment took place between Oct 1, 2016, and June 30, 2018; in Papua New Guinea, recruitment was between Dec 1, 2016, and Aug 31, 2018. A total of 393 caregiver-infant pairs were enrolled in the study across both countries. Independent of study time, the Xpert test reduced time to early infant diagnosis results communication by 60%, compared with the standard of care (adjusted time ratio 0·40, 95% CI 0·29-0·53, p<0·0001). In the control phase, two (2%) of 102 study participants received an early infant diagnosis test result by 3 months of age compared with 214 (74%) of 291 in the intervention phase. No safety and adverse events were reported related to the diagnostic testing intervention. INTERPRETATION This study reinforces the importance of scaling up point-of-care early infant diagnosis testing in resource-constrained and low HIV-prevalence settings, typical of the UNICEF East Asia and Pacific region. FUNDING National Health and Medical Research Council of Australia.
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Affiliation(s)
- Yasmin Mohamed
- Burnet Institute, Melbourne, VIC, Australia; Murdoch Children's Research Institute, Melbourne, VIC, Australia.
| | - Hla Htay
- Burnet Institute Myanmar, Yangon, Myanmar
| | - Janet Gare
- Sexual and Reproductive Health Unit, Papua New Guinea Institute of Medical Research, Goroka, Eastern Highlands Province, Papua New Guinea
| | - Andrew J B Vallely
- Sexual and Reproductive Health Unit, Papua New Guinea Institute of Medical Research, Goroka, Eastern Highlands Province, Papua New Guinea; Kirby Institute for Infection and Immunity in Society, Faculty of Medicine, University of New South Wales, Sydney, NSW, Australia
| | - Angela Kelly-Hanku
- Sexual and Reproductive Health Unit, Papua New Guinea Institute of Medical Research, Goroka, Eastern Highlands Province, Papua New Guinea; Kirby Institute for Infection and Immunity in Society, Faculty of Medicine, University of New South Wales, Sydney, NSW, Australia
| | | | - Paul A Agius
- Burnet Institute, Melbourne, VIC, Australia; Faculty of Health, Deakin University, Melbourne, VIC, Australia; Department of Epidemiology and Preventive Medicine, Monash University, Melbourne, VIC, Australia
| | - Steven G Badman
- Kirby Institute for Infection and Immunity in Society, Faculty of Medicine, University of New South Wales, Sydney, NSW, Australia
| | - Minh Duc Pham
- Burnet Institute, Melbourne, VIC, Australia; Department of Epidemiology and Preventive Medicine, Monash University, Melbourne, VIC, Australia
| | - Claire Nightingale
- School of Population and Global Health, University of Melbourne, Melbourne, VIC, Australia
| | - Xiang-Sheng Chen
- Chinese Academy of Medical Science, Institute of Dermatology and National Centre for STD Control, Nanjing, China
| | - Zure Kombati
- Sexual and Reproductive Health Unit, Papua New Guinea Institute of Medical Research, Goroka, Eastern Highlands Province, Papua New Guinea; Mount Hagen General Hospital, Mount Hagen, Western Highlands Province, Papua New Guinea
| | - Amelia Koata
- Sexual and Reproductive Health Unit, Papua New Guinea Institute of Medical Research, Goroka, Eastern Highlands Province, Papua New Guinea
| | - Gloria Munnull
- Sexual and Reproductive Health Unit, Papua New Guinea Institute of Medical Research, Goroka, Eastern Highlands Province, Papua New Guinea; Mount Hagen General Hospital, Mount Hagen, Western Highlands Province, Papua New Guinea
| | - Selina Silim
- Sexual and Reproductive Health Unit, Papua New Guinea Institute of Medical Research, Goroka, Eastern Highlands Province, Papua New Guinea
| | - Win Thein
- National Health Laboratory, Yangon, Myanmar
| | - Tin Maung Zaw
- National AIDS Program (Yangon Region), Ministry of Health and Sports, Yangon, Myanmar
| | | | | | | | | | | | - Stanley Luchters
- Burnet Institute, Melbourne, VIC, Australia; Department of Epidemiology and Preventive Medicine, Monash University, Melbourne, VIC, Australia; Centre for Sexual Health and HIV/AIDS Research (CeSHHAR), Harare, Zimbabwe; Liverpool School of Tropical Medicine, Liverpool, UK; International Centre for Reproductive Health, Department of Public Health and Primary Care, Ghent University, Ghent, Belgium
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Gawde N, Kamble S, Kurle S, Jagtap D, Goel N, Nikhare K, Kamble S, Gade S, Verma V, Singh R, Nerurkar S, Rajan S, Das C. Determinants of Turn-Around-Time for Early Infant Diagnosis of HIV Testing: Retrospective Analysis of National Level PCR Testing Data. INQUIRY : A JOURNAL OF MEDICAL CARE ORGANIZATION, PROVISION AND FINANCING 2023; 60:469580231159493. [PMID: 36932853 PMCID: PMC10026091 DOI: 10.1177/00469580231159493] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 03/19/2023]
Abstract
India has been implementing one of the biggest Early Infant Diagnosis (EID) of HIV intervention globally. The turn-around-time (TAT) for EID test is one of the major factors for success of the program. This study was to assess the turnaround time and its determinants. It is a mixed methods study with quantitative analysis of retrospective data (2013-2016) collected from all the 7 Early Infant Diagnosis testing laboratories (called as regional reference laboratories or RRLs) in India and qualitative component that can help explain the determinants of turn-around-time. The retrospective national level data available from the RRLs was analyzed to measure the turn-around-time from the receipt of samples to the dispatch of results and to understand the determinants for the same. The 3 components transport time, testing time, and dispatch time were also calculated. Transport time was analyzed state-wise and the testing time RRL wise to understand disparities, if any. Qualitative interviews with the RRL officials were conducted to understand the underlying determinants of TAT. The Median turn-around-time ranged between 29 and 53 days over the 4 years. Transport time was significantly higher for states without RRL (42 days) than those with RRL (27 days). Testing time varied from RRL to RRL and was associated with incomplete forms, inadequate samples, kits logistics, staff turnover, staff training, and instrument related issues. The TAT is high and can be potentially reduced with interventions, such as decentralization of RRLs; courier systems for sample transport; and ensuring adequate resources at the RRL level.
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Affiliation(s)
- Nilesh Gawde
- Tata Institute of Social Sciences, Mumbai, Maharashtra, India
| | - Suchit Kamble
- ICMR - National AIDS Research Institute, Pune, Maharashtra, India
| | - Swarali Kurle
- ICMR - National AIDS Research Institute, Pune, Maharashtra, India
| | - Dhanashree Jagtap
- ICMR - National Institute for Research in Reproductive Health, Mumbai, Maharashtra, India
| | - Noopur Goel
- ICMR - National AIDS Research Institute, Pune, Maharashtra, India
| | - Kalyani Nikhare
- ICMR - National AIDS Research Institute, Pune, Maharashtra, India
| | - Susmita Kamble
- ICMR - National AIDS Research Institute, Pune, Maharashtra, India
| | - Sharda Gade
- ICMR - National AIDS Research Institute, Pune, Maharashtra, India
| | - Vinita Verma
- National AIDS Control Organisation, New Delhi, India
| | - Ravikar Singh
- Tata Institute of Social Sciences, Mumbai, Maharashtra, India
| | - Sayali Nerurkar
- Tata Institute of Social Sciences, Mumbai, Maharashtra, India
| | - Shobini Rajan
- National AIDS Control Organisation, New Delhi, India
| | - Chinmoyee Das
- National AIDS Control Organisation, New Delhi, India
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Jacobson TA, Kler JS, Bae Y, Chen J, Ladror DT, Iyer R, Nunes DA, Montgomery ND, Pleil JD, Funk WE. A state-of-the-science review and guide for measuring environmental exposure biomarkers in dried blood spots. JOURNAL OF EXPOSURE SCIENCE & ENVIRONMENTAL EPIDEMIOLOGY 2022:10.1038/s41370-022-00460-7. [PMID: 35963945 PMCID: PMC9375076 DOI: 10.1038/s41370-022-00460-7] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 12/05/2021] [Revised: 07/14/2022] [Accepted: 07/21/2022] [Indexed: 05/11/2023]
Abstract
BACKGROUND Dried blood spot (DBS) sampling is a simple, cost-effective, and minimally invasive alternative to venipuncture for measuring exposure biomarkers in public health and epidemiological research. DBS sampling provides advantages in field-based studies conducted in low-resource settings and in studies involving infants and children. In addition, DBS samples are routinely collected from newborns after birth (i.e., newborn dried blood spots, NDBS), with many states in the United States permitting access to archived NDBS samples for research purposes. OBJECTIVES We review the state of the science for analyzing exposure biomarkers in DBS samples, both archived and newly collected, and provide guidance on sample collection, storage, and blood volume requirements associated with individual DBS assays. We discuss recent progress regarding analytical methods, analytical sensitivity, and specificity, sample volume requirements, contamination considerations, estimating extracted blood volumes, assessing stability and analyte recovery, and hematocrit effects. METHODS A systematic search of PubMed (MEDLINE), Embase (Elsevier), and CINAHL (EBSCO) was conducted in March 2022. DBS method development and application studies were divided into three main chemical classes: environmental tobacco smoke, trace elements (including lead, mercury, cadmium, and arsenic), and industrial chemicals (including endocrine-disrupting chemicals and persistent organic pollutants). DBS method development and validation studies were scored on key quality-control and performance parameters by two members of the review team. RESULTS Our search identified 47 published reports related to measuring environmental exposure biomarkers in human DBS samples. A total of 28 reports (37 total studies) were on methods development and validation and 19 reports were primarily the application of previously developed DBS assays. High-performing DBS methods have been developed, validated, and applied for detecting environmental exposures to tobacco smoke, trace elements, and several important endocrine-disrupting chemicals and persistent organic pollutants. Additional work is needed for measuring cadmium, arsenic, inorganic mercury, and bisphenol A in DBS and NDBS samples. SIGNIFICANCE We present an inventory and critical review of available assays for measuring environmental exposure biomarkers in DBS and NDBS samples to help facilitate this sampling medium as an emerging tool for public health (e.g., screening programs, temporal biomonitoring) and environmental epidemiology (e.g., field-based studies).
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Affiliation(s)
- Tyler A Jacobson
- Department of Preventive Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL, USA
| | - Jasdeep S Kler
- University of Michigan Medical School, Ann Arbor, MI, USA
| | - Yeunook Bae
- Department of Preventive Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL, USA
| | - Jiexi Chen
- Department of Preventive Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL, USA
| | - Daniel T Ladror
- Department of Preventive Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL, USA
| | - Ramsunder Iyer
- Department of Preventive Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL, USA
| | - Denise A Nunes
- Galter Health Sciences Library, Northwestern University Feinberg School of Medicine, Chicago, IL, USA
| | - Nathan D Montgomery
- Department of Preventive Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL, USA
| | - Joachim D Pleil
- Department of Environmental Sciences and Engineering, Gillings School of Public Health, University of North Carolina, Chapel Hill, NC, USA
| | - William E Funk
- Department of Preventive Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL, USA.
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Ochodo EA, Guleid F, Deeks JJ, Mallett S. Point-of-care tests detecting HIV nucleic acids for diagnosis of HIV-1 or HIV-2 infection in infants and children aged 18 months or less. Cochrane Database Syst Rev 2021; 8:CD013207. [PMID: 34383961 PMCID: PMC8406580 DOI: 10.1002/14651858.cd013207.pub2] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/30/2022]
Abstract
BACKGROUND The standard method of diagnosing HIV in infants and children less than 18 months is with a nucleic acid amplification test reverse transcriptase polymerase chain reaction test (NAT RT-PCR) detecting viral ribonucleic acid (RNA). Laboratory testing using the RT-PCR platform for HIV infection is limited by poor access, logistical support, and delays in relaying test results and initiating therapy in low-resource settings. The use of rapid diagnostic tests at or near the point-of-care (POC) can increase access to early diagnosis of HIV infection in infants and children less than 18 months of age and timely initiation of antiretroviral therapy (ART). OBJECTIVES To summarize the diagnostic accuracy of point-of-care nucleic acid-based testing (POC NAT) to detect HIV-1/HIV-2 infection in infants and children aged 18 months or less exposed to HIV infection. SEARCH METHODS We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (until 2 February 2021), MEDLINE and Embase (until 1 February 2021), and LILACS and Web of Science (until 2 February 2021) with no language or publication status restriction. We also searched conference websites and clinical trial registries, tracked reference lists of included studies and relevant systematic reviews, and consulted experts for potentially eligible studies. SELECTION CRITERIA We defined POC tests as rapid diagnostic tests conducted at or near the patient site. We included any primary study that compared the results of a POC NAT to a reference standard of laboratory NAT RT-PCR or total nucleic acid testing to detect the presence or absence of HIV infection denoted by HIV viral nucleic acids in infants and children aged 18 months or less who were exposed to HIV-1/HIV-2 infection. We included cross-sectional, prospective, and retrospective study designs and those that provided sufficient data to create the 2 × 2 table to calculate sensitivity and specificity. We excluded diagnostic case control studies with healthy controls. DATA COLLECTION AND ANALYSIS We extracted information on study characteristics using a pretested standardized data extraction form. We used the QUADAS-2 (Quality Assessment of Diagnostic Accuracy Studies) tool to assess the risk of bias and applicability concerns of the included studies. Two review authors independently selected and assessed the included studies, resolving any disagreements by consensus. The unit of analysis was the participant. We first conducted preliminary exploratory analyses by plotting estimates of sensitivity and specificity from each study on forest plots and in receiver operating characteristic (ROC) space. For the overall meta-analyses, we pooled estimates of sensitivity and specificity using the bivariate meta-analysis model at a common threshold (presence or absence of infection). MAIN RESULTS We identified a total of 12 studies (15 evaluations, 15,120 participants). All studies were conducted in sub-Saharan Africa. The ages of included infants and children in the evaluations were as follows: at birth (n = 6), ≤ 12 months (n = 3), ≤ 18 months (n = 5), and ≤ 24 months (n = 1). Ten evaluations were field evaluations of the POC NAT test at the point of care, and five were laboratory evaluations of the POC NAT tests.The POC NAT tests evaluated included Alere q HIV-1/2 Detect qualitative test (recently renamed m-PIMA q HIV-1/2 Detect qualitative test) (n = 6), Xpert HIV-1 qualitative test (n = 6), and SAMBA HIV-1 qualitative test (n = 3). POC NAT pooled sensitivity and specificity (95% confidence interval (CI)) against laboratory reference standard tests were 98.6% (96.1 to 99.5) (15 evaluations, 1728 participants) and 99.9% (99.7 to 99.9) (15 evaluations, 13,392 participants) in infants and children ≤ 18 months. Risk of bias in the included studies was mostly low or unclear due to poor reporting. Five evaluations had some concerns for applicability for the index test, as they were POC tests evaluated in a laboratory setting, but there was no difference detected between settings in sensitivity (-1.3% (95% CI -4.1 to 1.5)); and specificity results were similar. AUTHORS' CONCLUSIONS For the diagnosis of HIV-1/HIV-2 infection, we found the sensitivity and specificity of POC NAT tests to be high in infants and children aged 18 months or less who were exposed to HIV infection.
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Affiliation(s)
- Eleanor A Ochodo
- Centre for Global Health Research, Kenya Medical Research Institute, Kisumu, Kenya
- Centre for Evidence-based Health Care, Department of Global Health, Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town, South Africa
| | - Fatuma Guleid
- KEMRI-Wellcome Trust Research Programme, Nairobi, Kenya
| | - Jonathan J Deeks
- Test Evaluation Research Group, Institute of Applied Health Research, University of Birmingham, Birmingham, UK
| | - Sue Mallett
- UCL Centre for Medical Imaging, Division of Medicine, Faculty of Medical Sciences, University College London, London, UK
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Nuoh RD, Nyarko KM, Noora CL, Addo-Lartey A, Nortey P, Nuolabong C, Lartey M, Kenu E. Barriers to early infant diagnosis of HIV in the Wa Municipality and Lawra District of Upper West Region, Ghana. Ghana Med J 2021; 54:83-90. [PMID: 33536673 PMCID: PMC7837354 DOI: 10.4314/gmj.v54i2s.13] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022] Open
Abstract
Objective We identified socio-demographic, health system and psycho-social barriers to Early Infant Diagnosis (EID) of HIV in the Upper West Region of Ghana. Design An unmatched case control study of 96 cases and 96 controls was conducted in the ART centers in Lawra district and Wa Municipality between December 2014 and April 2015. Setting A public health facility Participants We defined a case as an HIV positive mother with an exposed infant who received EID service between January 2011 and December 2014. A control was defined as HIV Positive Mother with an exposed infant who did not receive EID services between January 2011 and December 2014. Main outcome EID by dry blood spot Deoxyribonucleic acid Polymerase chain reaction. Results A total of 192 mother-infant pairs were assessed. The mean age of infants at testing for cases was 17.3±14.9 weeks. Mother-to-child-transmission-rate was 2.3%. Factors associated with EID testing included: mother being formally employed (cOR=2.0: 95%CI:1.1–3.8), maternal formal education (cOR=2.0, 95%CI: 1.1–3.6) and maternal independent source of income (cOR 2.2, 95%CI 1.2–4.1). After adjusting for confounders, maternal independent income source was associated with EID testing (aOR 2.2, 95%CI 1.2–4.1). Median turn-around time of EID result was 11 weeks (IQR 4–27 weeks). Conclusion Women need to be empowered to gain an independent source of income. This can help maximize the benefits of e-MTCT and increase EID in the Upper West Region of Ghana. Funding This work was funded by the authors
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Affiliation(s)
- Robert D Nuoh
- Ghana Field Epidemiology and Laboratory Training Program, Department of Epidemiology, School of Public Health, College of Health Sciences, University of Ghana Legon, Accra, Ghana
| | - Kofi M Nyarko
- Namibia Field Epidemiology and Laboratory Training Program, University of Namibia, Windhoek, Namibia
| | - Charles L Noora
- Ghana Field Epidemiology and Laboratory Training Program, Department of Epidemiology, School of Public Health, College of Health Sciences, University of Ghana Legon, Accra, Ghana
| | - Adolphina Addo-Lartey
- Ghana Field Epidemiology and Laboratory Training Program, Department of Epidemiology, School of Public Health, College of Health Sciences, University of Ghana Legon, Accra, Ghana
| | - Priscillia Nortey
- Ghana Field Epidemiology and Laboratory Training Program, Department of Epidemiology, School of Public Health, College of Health Sciences, University of Ghana Legon, Accra, Ghana
| | - Culbert Nuolabong
- Ghana Field Epidemiology and Laboratory Training Program, Department of Epidemiology, School of Public Health, College of Health Sciences, University of Ghana Legon, Accra, Ghana
| | - Margaret Lartey
- Department of Medicine and Therapeutics, School of Medicine and Dentistry, College of Health Sciences, University of Ghana, Korle Bu, Accra, Ghana
| | - Ernest Kenu
- Ghana Field Epidemiology and Laboratory Training Program, Department of Epidemiology, School of Public Health, College of Health Sciences, University of Ghana Legon, Accra, Ghana.,Department of Medicine and Therapeutics, School of Medicine and Dentistry, College of Health Sciences, University of Ghana, Korle Bu, Accra, Ghana
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12
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Yumo HA, Ndenkeh JN, Sieleunou I, Nsame DN, Kuwoh PB, Beissner M, Loscher T, Kuaban C. Human immunodeficiency virus case detection and antiretroviral therapy enrollment among children below and above 18 months old: A comparative analysis from Cameroon. Medicine (Baltimore) 2021; 100:e25510. [PMID: 33907100 PMCID: PMC8084087 DOI: 10.1097/md.0000000000025510] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/12/2020] [Revised: 03/19/2021] [Accepted: 03/24/2021] [Indexed: 11/26/2022] Open
Abstract
ABSTRACT While pediatric human immunodeficiency virus (HIV) testing has been more focused on children below 18 months through prevention of mother to child transmission of HIV (PMTCT), the yield of this approach remains unclear comparatively to testing children above 18 months through routine provider-initiated testing and counselling (PITC). This study aimed at assessing and comparing the HIV case detection and antiretroviral therapy (ART) enrolment among children below and above 18 months of age in Cameroon. This information is required to guide the investments in HIV testing among children and adolescents.We conducted a cross-sectional study where we invited parents visiting or receiving HIV care in 3 hospitals to have their children tested for HIV. HIV testing was done using polymerase chain reaction (PCR) and antibody rapid tests for children <18 months and those ≥18 months, respectively. We compared HIV case detection and ART initiation between the 2 subgroups of children and this using Chi-square test at 5% significant level.A total of 4079 children aged 6 weeks to 15 years were included in the analysis. Compared with children <18 months, children group ≥18 months was 4-fold higher among those who enrolled in the study (80.3% vs 19.7%, P < .001); 3.5-fold higher among those who tested for HIV (77.6% vs 22.4%, P < .001); 6-fold higher among those who tested HIV+ (85.7% vs 14.3%, P = .24), and 11-fold higher among those who enrolled on ART (91.7% vs 8.3%, P = .02).Our results show that 4 out of 5 children who tested HIV+ and over 90% of ART enrolled cases were children ≥18 months. Thus, while rolling out PCR HIV testing technology for neonates and infants, committing adequate and proportionate resources in antibody rapid testing for older children is a sine quo none condition to achieve an acquired immunodeficiency syndrome (AIDS)-free generation.
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Affiliation(s)
- Habakkuk A. Yumo
- R4D International Foundation, Yaoundé
- Ludwig Maximilian University, Munich, Germany
| | - Jackson N. Ndenkeh
- R4D International Foundation, Yaoundé
- Ludwig Maximilian University, Munich, Germany
| | - Isidore Sieleunou
- R4D International Foundation, Yaoundé
- University of Montreal, Montreal, Canada
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Estimating the Cost of Point-of-Care Early Infant Diagnosis in a Program Setting: A Case Study Using Abbott m-PIMA and Cepheid GeneXpert IV in Zimbabwe. J Acquir Immune Defic Syndr 2021; 84 Suppl 1:S63-S69. [PMID: 32520917 DOI: 10.1097/qai.0000000000002371] [Citation(s) in RCA: 12] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
Abstract
BACKGROUND Point-of-care early infant diagnosis (POC EID) increases access to HIV test results and shortens time to result-return and antiretroviral therapy initiation, as compared to central laboratory-based EID. However, to scale-up POC EID, governments need more information about programmatic costs. METHODS We evaluated POC EID costs from a health systems perspective. Our primary analysis assessed the Abbott m-PIMA and 2 versions of the Cepheid GeneXpert IV platforms-with a solar battery or gel battery-used in Zimbabwe, with instrument purchase. We also included the following 2 scenarios with zero upfront equipment purchase: (1) m-PIMA using a reagent rental model, with an all-inclusive price when the buyer commits to an average testing volume, and (2) GeneXpert IV, reflecting contexts where GeneXpert is already in place for tuberculosis diagnosis or HIV viral load monitoring. We collected data from project expenditures, observations of health workers, and from government salary scales. We calculated cost per EID test based on number of EID tests performed on each machine per day. RESULTS The cost per successfully completed test was $44.55 for m-PIMA with platform purchase and $25.89 for m-PIMA reagent rental. Costs for GeneXpert IV with platform purchase were $25.70 using a solar battery, $25.29 using a gel battery, and $23.85 under a scenario assuming no equipment costs. In our primary analyses, materials costs comprised 73%-74% total costs, equipment 14%-20%, labor 5%-8%, training 1%, facility upgrades 1%, and monitoring 1%. CONCLUSIONS As countries consider scaling up POC EID, these data are important for budgeting and planning.
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Front-Line Human Resource Time-Use for Early Infant HIV Diagnosis: A Comparative Time-Motion Study at Centralized and Point-of-Care Health Facilities in Zimbabwe. J Acquir Immune Defic Syndr 2021; 84 Suppl 1:S70-S77. [PMID: 32520918 DOI: 10.1097/qai.0000000000002364] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/27/2022]
Abstract
BACKGROUND Point-of-care (POC) assays for early infant diagnosis of HIV (EID) increase access to testing, shorten time to results, and expedite initiation of antiretroviral therapy when compared with laboratory-based assays. However, there is a significant gap in our understanding of its human resource impact at the facility level. This study evaluates front-line health workers' (HWs') time associated with EID. SETTING Using time-motion methodology, we collected time-use data on EID tasks performed by HWs at 3 EID facility types in Zimbabwe-5 POC hubs, 9 POC spokes, and 11 facilities that used centralized laboratories. METHODS Data collectors observed 30 EID processes and 30 HWs' provided self-reported time. Comparisons of mean differences of HWs' time-use between centralized and POC EID were performed with a 2-sample t test with unequal variances. RESULTS Observed average total labor time per EID test at POC facilities was 28 minutes, 22 seconds [95% confidence interval (CI): 22:51 to 35:48], which was equivalent to the average preresult time at facilities using centralized EID. HWs performed other tasks while the machine processed samples. Observed average preresult time (counseling to sample preparation) was 18 minutes, 6 Supported by seconds (95% CI: 13:00 to 23:42) for POC compared with 27 minutes, 48 seconds (95% CI: 23:48 to 32:50) for facilities using centralized laboratories. The mean difference of 9 minutes, 42 seconds (95% CI: 03:04 to 16:18) was statistically significant. The differences in self-reported average total labor time per EID test between HWs at facilities using centralized laboratories or POC were not statistically significant. CONCLUSION Use of POC assays did not incur additional human resource time compared with sending dried blood spots to a centralized laboratory for EID.
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Mofenson LM, Cohn J, Sacks E. Challenges in the Early Infant HIV Diagnosis and Treatment Cascade. J Acquir Immune Defic Syndr 2021; 84 Suppl 1:S1-S4. [PMID: 32520908 DOI: 10.1097/qai.0000000000002366] [Citation(s) in RCA: 13] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/25/2022]
Abstract
The first step in improving morbidity and mortality among children living with HIV is the timely and early identification of HIV infection, which must be followed by rapid engagement in care and provision of antiretroviral therapy. However, in 2018, only 59% of HIV-exposed infants received an infant nucleic acid diagnostic test by age 2 months and only 54% of children living with HIV received treatment. Because infant diagnosis requires molecular techniques to detect viral nucleic acid, programs for early diagnosis of infection in infants are more complex than those in adults and often require coordination and management of multiple health facilities as well as logistic, financial, and human resource challenges. This article will discuss challenges at each step in the early infant diagnosis cascade and innovations that may help overcome these challenges.
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Affiliation(s)
- Lynne M Mofenson
- Department of Research, Elizabeth Glaser Pediatric AIDS Foundation, Washington, DC
| | - Jennifer Cohn
- Department of Innovation and New Technology, Elizabeth Glaser Pediatric AIDS Foundation, Geneva, Switzerland; and.,Division of Infectious Diseases, University of Pennsylvania School of Medicine, Philadelphia, PA
| | - Emma Sacks
- Department of Research, Elizabeth Glaser Pediatric AIDS Foundation, Washington, DC
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Ankrah AK, Dako-Gyeke P. Factors influencing the delivery and uptake of early infant diagnosis of HIV services in Greater Accra, Ghana: A qualitative study. PLoS One 2021; 16:e0246876. [PMID: 33596241 PMCID: PMC7888588 DOI: 10.1371/journal.pone.0246876] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/30/2020] [Accepted: 01/27/2021] [Indexed: 11/18/2022] Open
Abstract
BACKGROUND Early Infant Diagnosis (EID) of HIV and timely initiation of Antiretroviral Therapy (ART) can significantly reduce morbidity and mortality of HIV infected infants. Despite the benefits of early infant testing, the coverage of EID of HIV services is still low in Sub-Saharan Africa, including Ghana. OBJECTIVES To ascertain the factors that facilitate or hinder the delivery and uptake of EID of HIV services. METHODS The study is a cross-sectional exploratory qualitative research conducted in two health facilities in the Greater Accra Region of Ghana. Respondents (n = 50) comprising health workers (n = 20) and HIV positive mothers (n = 30) were purposively sampled and engaged in in-depth interviews. The Nvivo 11 software and the Braun and Clarke's stages of thematic analysis were used in coding data and data analysis respectively. RESULTS The study found that health system factors such as inadequate Staff with sample collection skills, unavailability of vehicles to convey samples to the reference laboratory for analysis, the long turnaround time for receipt of Polymerase Chain Reaction (PCR) results, inadequate and frequent breakdown of PCR machine hindered EID service delivery. On the other hand, adequate knowledge of health workers on EID, availability of Dried Blood Spot (DBS) cards and the adoption of task shifting strategies facilitated EID service delivery. Factors such as the denial of HIV status, non-completion of the EID process due to frustrations encountered whiles accessing service and delay in receipt of PCR results served as barriers to mother's utilisation of EID services for their exposed infants. The study also identified that adequate knowledge of EID, perceived importance of EID, financial stability as well as financial support from others and the positive attitudes of health workers facilitated HIV positive mother's uptake of EID services for their exposed infants. CONCLUSION The factors attributing to the low coverage of EID of HIV services must be promptly addressed to improve service delivery and uptake.
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Affiliation(s)
- Antoinette Kailey Ankrah
- Department of Social and Behavioural Sciences, School of Public Health, College of Health Sciences, University of Ghana, Accra, Ghana
- * E-mail:
| | - Phyllis Dako-Gyeke
- Department of Social and Behavioural Sciences, School of Public Health, College of Health Sciences, University of Ghana, Accra, Ghana
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Uganda's "EID Systems Strengthening" model produces significant gains in testing, linkage, and retention of HIV-exposed and infected infants: An impact evaluation. PLoS One 2021; 16:e0246546. [PMID: 33539425 PMCID: PMC7861549 DOI: 10.1371/journal.pone.0246546] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/30/2020] [Accepted: 01/20/2021] [Indexed: 11/19/2022] Open
Abstract
Introduction A review of Uganda’s HIV Early Infant Diagnosis (EID) program in 2010 revealed poor retention outcomes for HIV-exposed infants (HEI) after testing. The review informed development of the ‘EID Systems Strengthening’ model: a set of integrated initiatives at health facilities to improve testing, retention, and clinical care of HIV-exposed and infected infants. The program model was piloted at several facilities and later scaled countrywide. This mixed-methods study evaluates the program’s impact and assesses its implementation. Methods We conducted a retrospective cohort study at 12 health facilities in Uganda, comprising all HEI tested by DNA PCR from June 2011 to May 2014 (n = 707). Cohort data were collected manually at the health facilities and analyzed. To assess impact, retention outcomes were statistically compared to the baseline study’s cohort outcomes. We conducted a cross-sectional qualitative assessment of program implementation through 1) structured clinic observation and 2) key informant interviews with health workers, district officials, NGO technical managers, and EID trainers (n = 51). Results The evaluation cohort comprised 707 HEI (67 HIV+). The baseline study cohort contained 1268 HEI (244 HIV+). Among infants testing HIV+, retention in care at an ART clinic increased from 23% (57/244) to 66% (44/67) (p < .0001). Initiation of HIV+ infants on ART increased from 36% (27/75) to 92% (46/50) (p < .0001). HEI receiving 1st PCR results increased from 57% (718/1268) to 73% (518/707) (p < .0001). Among breastfeeding HEI with negative 1st PCR, 55% (192/352) received a confirmatory PCR test, a substantial increase from baseline period. Testing coverage improved significantly: HIV+ pregnant women who brought their infants for testing after birth increased from 18% (67/367) to 52% (175/334) (p < .0001). HEI were tested younger: mean age at DBS test decreased from 6.96 to 4.21 months (p < .0001). Clinical care for HEI was provided more consistently. Implementation fidelity was strong for most program components. The strongest contributory interventions were establishment of ‘EID Care Points’, integration of clinical care, longitudinal patient tracking, and regular health worker mentorship. Gaps included limited follow up of lost infants, inconsistent buy-in/ownership of health facility management, and challenges sustaining health worker motivation. Discussion Uganda’s ‘EID Systems Strengthening’ model has produced significant gains in testing and retention of HEI and HIV+ infants, yet the country still faces major challenges. The 3 core concepts of Uganda’s model are applicable to any country: establish a central service point for HEI, equip it to provide high-quality care and tracking, and develop systems to link HEI to the service point. Uganda’s experience has shown the importance of intensively targeting systemic bottlenecks to HEI retention at facility level, a necessary complement to deploying rapidly scalable technologies and other higher-level initiatives.
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Chinguwo F, Nyondo-Mipando AL. Integration of Early Infant Diagnosis of HIV Services Into Village Health Clinics in Ntcheu, Malawi: An Exploratory Qualitative Study. J Int Assoc Provid AIDS Care 2021; 20:2325958220981256. [PMID: 33557679 PMCID: PMC7876752 DOI: 10.1177/2325958220981256] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/30/2020] [Revised: 11/06/2020] [Accepted: 11/24/2020] [Indexed: 11/17/2022] Open
Abstract
Integration of Early Infant Diagnosis(EID) of HIV into Village Health Clinics (VHCs) would increase the uptake of services. This study assessed mothers and health care workers' acceptability of integration of EID of HIV services into VHCs in Ntcheu, Malawi. We conducted an exploratory qualitative study in the phenomenological tradition among 20 mothers of either HIV exposed or non-exposed infants and 18 health care workers (HCWs) from February to July 2019. We analyzed the data using a thematic approach and guided by the theoretical framework for acceptability. There were positive perceptions of the integration of services. Acceptability is influenced by attitudes, perceived burden, intervention coherent services, and perceived effectiveness of services. The successful integration of EID of HIV into VHCs requires strengthening of the health system and community awareness. Efforts to mitigate stigma should be prioritized when integrating the services to optimize uptake of the services at a community level.
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Affiliation(s)
- Felix Chinguwo
- Department of Public health, School of Public Health and
Family Medicine, College of Medicine, Blantyre, Malawi
| | - Alinane Linda Nyondo-Mipando
- Department of Health Systems and Policy, School of Public
Health and Family Medicine, College of Medicine, Blantyre, Malawi
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Dunning L, Gandhi AR, Penazzato M, Soeteman DI, Revill P, Frank S, Phillips A, Dugdale C, Abrams E, Weinstein MC, Newell M, Collins IJ, Doherty M, Vojnov L, Fassinou Ekouévi P, Myer L, Mushavi A, Freedberg KA, Ciaranello AL. Optimizing infant HIV diagnosis with additional screening at immunization clinics in three sub-Saharan African settings: a cost-effectiveness analysis. J Int AIDS Soc 2021; 24:e25651. [PMID: 33474817 PMCID: PMC8992471 DOI: 10.1002/jia2.25651] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/09/2020] [Revised: 10/19/2020] [Accepted: 11/17/2020] [Indexed: 11/22/2022] Open
Abstract
INTRODUCTION Uptake of early infant HIV diagnosis (EID) varies widely across sub-Saharan African settings. We evaluated the potential clinical impact and cost-effectiveness of universal maternal HIV screening at infant immunization visits, with referral to EID and maternal antiretroviral therapy (ART) initiation. METHODS Using the CEPAC-Pediatric model, we compared two strategies for infants born in 2017 in Côte d'Ivoire (CI), South Africa (SA), and Zimbabwe: (1) existing EID programmes offering six-week nucleic acid testing (NAT) for infants with known HIV exposure (EID), and (2) EID plus universal maternal HIV screening at six-week infant immunization visits, leading to referral for infant NAT and maternal ART initiation (screen-and-test). Model inputs included published Ivoirian/South African/Zimbabwean data: maternal HIV prevalence (4.8/30.8/16.1%), current uptake of EID (40/95/65%) and six-week immunization attendance (99/74/94%). Referral rates for infant NAT and maternal ART initiation after screen-and-test were 80%. Costs included NAT ($24/infant), maternal screening ($10/mother-infant pair), ART ($5 to 31/month) and HIV care ($15 to 190/month). Model outcomes included mother-to-child transmission of HIV (MTCT) among HIV-exposed infants, and life expectancy (LE) and mean lifetime per-person costs for children with HIV (CWH) and all children born in 2017. We calculated incremental cost-effectiveness ratios (ICERs) using discounted (3%/year) lifetime costs and LE for all children. We considered two cost-effectiveness thresholds in each country: (1) the per-capita GDP ($1720/6380/2150) per year-of-life saved (YLS), and (2) the CEPAC-generated ICER of offering 2 versus 1 lifetime ART regimens (e.g. offering second-line ART; $520/500/580/YLS). RESULTS With EID, projected six-week MTCT was 9.3% (CI), 4.2% (SA) and 5.2% (Zimbabwe). Screen-and-test decreased total MTCT by 0.2% to 0.5%, improved LE by 2.0 to 3.5 years for CWH and 0.03 to 0.07 years for all children, and increased discounted costs by $17 to 22/child (all children). The ICER of screen-and-test compared to EID was $1340/YLS (CI), $650/YLS (SA) and $670/YLS (Zimbabwe), below the per-capita GDP but above the ICER of 2 versus 1 lifetime ART regimens in all countries. CONCLUSIONS Universal maternal HIV screening at immunization visits with referral to EID and maternal ART initiation may reduce MTCT, improve paediatric LE, and be of comparable value to current HIV-related interventions in high maternal HIV prevalence settings like SA and Zimbabwe.
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Affiliation(s)
- Lorna Dunning
- Medical Practice Evaluation CenterMassachusetts General HospitalBostonMAUSA
| | - Aditya R Gandhi
- Medical Practice Evaluation CenterMassachusetts General HospitalBostonMAUSA
| | - Martina Penazzato
- Global HIV, Hepatitis, and STIs ProgrammeWorld Health OrganizationGenevaSwitzerland
| | - Djøra I Soeteman
- Medical Practice Evaluation CenterMassachusetts General HospitalBostonMAUSA
- Center for Health Decision ScienceHarvard T.H. Chan School of Public HealthBostonMAUSA
| | - Paul Revill
- Center for Health EconomicsUniversity of YorkYorkUnited Kingdom
| | - Simone Frank
- Medical Practice Evaluation CenterMassachusetts General HospitalBostonMAUSA
| | - Andrew Phillips
- Institute for Global HealthUniversity College LondonLondonUnited Kingdom
| | - Caitlin Dugdale
- Medical Practice Evaluation CenterMassachusetts General HospitalBostonMAUSA
- Division of Infectious DiseasesMassachusetts General HospitalBostonMAUSA
- Harvard Medical SchoolBostonMAUSA
| | - Elaine Abrams
- Mailman School of Public HealthICAP at Columbia UniversityNew York CityNYUSA
| | - Milton C Weinstein
- Center for Health Decision ScienceHarvard T.H. Chan School of Public HealthBostonMAUSA
| | - Marie‐Louise Newell
- Institute for Development StudiesHuman Development and HealthFaculty of MedicineUniversity of SouthamptonSouthamptonUnited Kingdom
- School of Public HealthFaculty of Health SciencesUniversity of WitwatersrandJohannesburgSouth Africa
| | - Intira J Collins
- Medical Research Council Clinical Trials UnitUniversity College LondonLondonUnited Kingdom
| | - Meg Doherty
- Global HIV, Hepatitis, and STIs ProgrammeWorld Health OrganizationGenevaSwitzerland
| | - Lara Vojnov
- Global HIV, Hepatitis, and STIs ProgrammeWorld Health OrganizationGenevaSwitzerland
| | | | - Landon Myer
- Division of Epidemiology & BiostatisticsSchool of Public Health & Family MedicineUniversity of Cape TownCape TownSouth Africa
| | | | - Kenneth A Freedberg
- Medical Practice Evaluation CenterMassachusetts General HospitalBostonMAUSA
- Division of Infectious DiseasesMassachusetts General HospitalBostonMAUSA
- Harvard Medical SchoolBostonMAUSA
| | - Andrea L Ciaranello
- Medical Practice Evaluation CenterMassachusetts General HospitalBostonMAUSA
- Division of Infectious DiseasesMassachusetts General HospitalBostonMAUSA
- Harvard Medical SchoolBostonMAUSA
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Mohamed Y, Kupul M, Gare J, Badman SG, Silim S, Vallely AJ, Luchters S, Kelly-Hanku A. Feasibility and acceptability of implementing early infant diagnosis of HIV in Papua New Guinea at the point of care: a qualitative exploration of health worker and key informant perspectives. BMJ Open 2020; 10:e043679. [PMID: 33444219 PMCID: PMC7678362 DOI: 10.1136/bmjopen-2020-043679] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/11/2020] [Revised: 10/27/2020] [Accepted: 10/28/2020] [Indexed: 11/23/2022] Open
Abstract
INTRODUCTION Early infant diagnosis (EID) of HIV and timely initiation of antiretroviral therapy can significantly reduce morbidity and mortality among HIV-positive infants. Access to EID is limited in many low-income and middle-income settings, particularly those in which standard care involves dried blood spots (DBS) sent to centralised laboratories, such as in Papua New Guinea (PNG). We conducted a qualitative exploration of the feasibility and acceptability of implementing a point-of-care (POC) EID test (Xpert HIV-1 Qualitative assay) among health workers and key stakeholders working within the prevention of mother-to-child transmission of HIV (PMTCT) programme in PNG. METHODS This qualitative substudy was conducted as part of a pragmatic trial to investigate the effectiveness of the Xpert HIV-1 Qualitative test for EID in PNG and Myanmar. Semistructured interviews were undertaken with 5 health workers and 13 key informants to explore current services, experiences of EID testing, perspectives on the Xpert test and the feasibility of integrating and scaling up POC EID in PNG. Coding was undertaken using inductive and deductive approaches, drawing on existing acceptability and feasibility frameworks. RESULTS Health workers and key informants (N=18) felt EID at POC was feasible to implement and beneficial to HIV-exposed infants and their families, staff and the PMTCT programme more broadly. All study participants highlighted starting HIV-positive infants on treatment immediately as the main advantage of POC EID compared with standard care DBS testing. Health workers identified insufficient resources to follow up infants and caregivers and space constraints in hospitals as barriers to implementation. Participants emphasised the importance of adequate human resources, ongoing training and support, appropriate coordination and a sustainable supply of consumables to ensure effective scale-up of the test throughout PNG. CONCLUSIONS Implementation of POC EID in a low HIV prevalence setting such as PNG is likely to be both feasible and beneficial with careful planning and adequate resources. TRIAL REGISTRATION NUMBER 12616000734460.
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Affiliation(s)
- Yasmin Mohamed
- Macfarlane Burnet Institute for Medical Research and Public Health, Melbourne, Victoria, Australia
- Department of Epidemiology and Preventive Medicine, School of Public Health and Preventive Medicine, Monash University, Melbourne, Victoria, Australia
| | - Martha Kupul
- Sexual and Reproductive Health Unit, Papua New Guinea Institute of Medical Research, Goroka, Papua New Guinea
| | - Janet Gare
- Sexual and Reproductive Health Unit, Papua New Guinea Institute of Medical Research, Goroka, Papua New Guinea
| | - Steven G Badman
- The Kirby Institute for Infection and Immunity in Society, UNSW Sydney, Sydney, New South Wales, Australia
| | - Selina Silim
- Sexual and Reproductive Health Unit, Papua New Guinea Institute of Medical Research, Goroka, Papua New Guinea
| | - Andrew J Vallely
- Sexual and Reproductive Health Unit, Papua New Guinea Institute of Medical Research, Goroka, Papua New Guinea
- The Kirby Institute for Infection and Immunity in Society, UNSW Sydney, Sydney, New South Wales, Australia
| | - Stanley Luchters
- Macfarlane Burnet Institute for Medical Research and Public Health, Melbourne, Victoria, Australia
- Department of Epidemiology and Preventive Medicine, School of Public Health and Preventive Medicine, Monash University, Melbourne, Victoria, Australia
- Department of Public Health and Primary Care, International Centre for Reproductive Health, Ghent University, Ghent, Belgium
- Department of Population Health, Aga Khan University, Nairobi, Kenya
| | - Angela Kelly-Hanku
- Sexual and Reproductive Health Unit, Papua New Guinea Institute of Medical Research, Goroka, Papua New Guinea
- The Kirby Institute for Infection and Immunity in Society, UNSW Sydney, Sydney, New South Wales, Australia
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Wubneh CA, Belay GM, Yehualashet FA, Tebeje NB, Mekonnen BD, Endalamaw A. Lost to Follow-up and Predictors Among HIV-Exposed Infants in Northwest Ethiopia. Infect Dis Ther 2020; 10:229-239. [PMID: 33113120 PMCID: PMC7592138 DOI: 10.1007/s40121-020-00360-z] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/13/2020] [Accepted: 10/14/2020] [Indexed: 11/19/2022] Open
Abstract
Introduction Even though advancement in mother-to-child HIV transmission prevention services is observed, many infants are lost to follow-up and could not access the full package of mother-to-child HIV transmission prevention services as a result. This is one of the obstacles to the effectiveness of the program. Therefore, determining the magnitude of lost to follow-up and its predictors is important among HIV-exposed infants. Method This institution-based retrospective cohort study was conducted from August 2013 to June 2018 at the University of Gondar Comprehensive Specialized Hospital. We retrieved charts of 423 child–mother pairs through a simple random sampling technique. Data collectors extracted data by using a data extraction tool adapted from the Ethiopian Federal Ministry of Health HIV-exposed infant follow-up form. Bivariable and multivariable Cox regression models were fitted to identify predictors of lost to follow-up. Result A total of 402 child–mother pairs were included in the study. Of the study participants, 6.0% were lost to follow-up for more than 3 months before the declaration of their HIV status. Born from rural residence mother (AHR = 3.5; 95% CI 1.549–7.894), infants whose mothers have three and more children (AHR = 3; 95% CI 1.284–6.963), and low birth weight infants (AHR = 3.2; 95% CI 1.055–9.450) were independent predictors of lost to follow-up among HIV-exposed infants. Conclusion Significant numbers of infants were unable to access full HIV diagnosis and care services as a result of loss to follow-up. Special consideration for mothers having large numbers of children, rural residence, and low birth weight infants could be an important intervention to decrease lost to follow-up.
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Affiliation(s)
- Chalachew Adugna Wubneh
- Department of Pediatrics and Child Health Nursing, School of Nursing, College of Medicine and Health Sciences, University of Gondar, Gondar, Ethiopia.
| | - Getaneh Mulualem Belay
- Department of Pediatrics and Child Health Nursing, School of Nursing, College of Medicine and Health Sciences, University of Gondar, Gondar, Ethiopia
| | - Fikadu Ambaw Yehualashet
- Unit of Community Health Nursing, School of Nursing, College of Medicine and Health Sciences, University of Gondar, Gondar, Ethiopia
| | - Nigusie Birhan Tebeje
- Unit of Community Health Nursing, School of Nursing, College of Medicine and Health Sciences, University of Gondar, Gondar, Ethiopia
| | | | - Aklilu Endalamaw
- Department of Pediatrics and Child Health Nursing, School of Health Sciences, College of Medicine and Health Sciences, Bahir Dar University, Bahir Dar, Ethiopia
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Wexler C, Nazir N, Maloba M, Brown M, Goggin K, Gautney B, Maosa N, Babu S, Muchoki E, Mabachi N, Lwembe R, Finocchario-Kessler S. Programmatic evaluation of feasibility and efficiency of at birth and 6-week, point of care HIV testing in Kenyan infant. PLoS One 2020; 15:e0240621. [PMID: 33035274 PMCID: PMC7546458 DOI: 10.1371/journal.pone.0240621] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/10/2020] [Accepted: 09/29/2020] [Indexed: 12/18/2022] Open
Abstract
Background Testing infants at birth and with more efficient point of care (POC) HIV diagnostic can streamline EID and expedite infant ART initiation. We evaluated the implementation of at birth and 6-week POC testing to assess the effectiveness and feasibility when implemented by existing hospital staff in Kenya. Methods Four government hospitals were randomly assigned to receive a GeneXpert HIV-1 Qual (n = 2) or Alere m-PIMA (n = 2) machine for POC testing. All HIV-exposed infants enrolled were eligible to receive POC testing at birth and 6-weeks of age. The primary outcome was repeat POC testing, defined as testing both at birth and 6-weeks of age. Secondary outcomes included predictors of repeat POC testing, POC efficiency (turnaround times of key services), and operations (failed POC results, missed opportunities). Results Of 626 enrolled infants, 309 (49.4%) received repeat POC testing, 115 (18.4%) were lost to follow up after an at-birth test, 120 (19.2%) received POC testing at 6-weeks only, 80 (12.8%) received no POC testing, and 2 (0.3%) received delayed POC testing (>12 weeks of age). Three (0.4%) were identified as HIV-positive. Of the total 853 POC tests run at birth (n = 424) or 6-weeks (n = 429), 806 (94.5%) had a valid result documented and 792 (98.3%) results had documented maternal notification. Mean time from sample collection to notification was 1.08 days, with 751 (94.8%) notifications on the same day as sample collection. Machine error rates at birth and 6-weeks were 8.5% and 2.5%, respectively. A total of 198 infants presented for care (48 at birth; 150 at 6-weeks) without receiving a POC test, representing missed opportunities for testing. Discussion At birth POC testing can streamline infant HIV diagnosis, expedite ART initiation and can be implemented by existing hospital staff. However, maternal disengagement and missed opportunities for testing must be addressed to realize the full benefits of at birth POC testing.
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Affiliation(s)
- Catherine Wexler
- Department of Family Medicine, University of Kansas Medical Center, Kansas City, KS, United States of America
- * E-mail:
| | - Niaman Nazir
- Department of Preventive Medicine, University of Kansas Medical Center, Kansas City, KS, United States of America
| | - May Maloba
- Global Health Innovations–Kenya, Nairobi, Kenya
| | - Melinda Brown
- Department of Family Medicine, University of Kansas Medical Center, Kansas City, KS, United States of America
| | - Kathy Goggin
- Children’s Mercy Kansas City, Health Services and Outcomes Research, Kansas City, MO, United States of America
- School of Medicine, University of Missouri-Kansas City, Kansas City, MO, United States of America
| | - Brad Gautney
- Global Health Innovations, Dallas, TX, United States of America
| | | | | | | | - Natabhona Mabachi
- Department of Family Medicine, University of Kansas Medical Center, Kansas City, KS, United States of America
| | | | - Sarah Finocchario-Kessler
- Department of Family Medicine, University of Kansas Medical Center, Kansas City, KS, United States of America
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Point of Care Diagnostics in Resource-Limited Settings: A Review of the Present and Future of PoC in Its Most Needed Environment. BIOSENSORS-BASEL 2020; 10:bios10100133. [PMID: 32987809 PMCID: PMC7598644 DOI: 10.3390/bios10100133] [Citation(s) in RCA: 50] [Impact Index Per Article: 10.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 08/27/2020] [Revised: 09/11/2020] [Accepted: 09/23/2020] [Indexed: 12/11/2022]
Abstract
Point of care (PoC) diagnostics are at the focus of government initiatives, NGOs and fundamental research alike. In high-income countries, the hope is to streamline the diagnostic procedure, minimize costs and make healthcare processes more efficient and faster, which, in some cases, can be more a matter of convenience than necessity. However, in resource-limited settings such as low-income countries, PoC-diagnostics might be the only viable route, when the next laboratory is hours away. Therefore, it is especially important to focus research into novel diagnostics for these countries in order to alleviate suffering due to infectious disease. In this review, the current research describing the use of PoC diagnostics in resource-limited settings and the potential bottlenecks along the value chain that prevent their widespread application is summarized. To this end, we will look at literature that investigates different parts of the value chain, such as fundamental research and market economics, as well as actual use at healthcare providers. We aim to create an integrated picture of potential PoC barriers, from the first start of research at universities to patient treatment in the field. Results from the literature will be discussed with the aim to bring all important steps and aspects together in order to illustrate how effectively PoC is being used in low-income countries. In addition, we discuss what is needed to improve the situation further, in order to use this technology to its fullest advantage and avoid “leaks in the pipeline”, when a promising device fails to take the next step of the valorization pathway and is abandoned.
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Kalawan V, Naidoo K, Archary M. Impact of routine birth early infant diagnosis on neonatal HIV treatment cascade in eThekwini district, South Africa. South Afr J HIV Med 2020; 21:1084. [PMID: 32537251 PMCID: PMC7276481 DOI: 10.4102/sajhivmed.v21i1.1084] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/05/2020] [Accepted: 03/19/2020] [Indexed: 12/13/2022] Open
Abstract
Background Early infant diagnosis (EID) of human immunodeficiency virus (HIV) and early initiation of antiretroviral therapy (ART) in HIV-infected infants can reduce the risk of mortality and improve clinical outcomes. Infant testing guidelines in KwaZulu-Natal, South Africa, changed from targeted birth EID (T-EID) only in high-risk infants to a routine birth EID (R-EID) testing strategy in 2015. Objectives To describe the impact of the implementation of R-EID on the infant treatment cascade. Method A retrospective analysis of a facility-based clinical database for the eThekwini district and the National Health Laboratory Services (NHLS) was conducted. All data on neonates (< 4 weeks of age) diagnosed with HIV between January 2013 and December 2017 (T-EID [2013-2015] and R-EID [2016-2017]) were extracted including follow-up until 1 year post-diagnosis. Results A total of 503 neonates were diagnosed HIV-infected, with 468 (93.0%) initiated on ART within a median of 6 days. There was a significant increase in the estimated percentage of HIV-infected neonates diagnosed (21% vs. 86%, p < 0.001) and initiated on ART (90% vs. 94.3%, p < 0.001) between the T-EID and R-EID periods. Despite achieving over 90% of HIV-infected neonates diagnosed and initiated on ART in 2017, retention in care and viral suppression remained low. Conclusion Implementation of R-EID in eThekwini district improved diagnosis and initiation of ART in HIV-infected neonates and should be recommended as part of diagnostic guidelines. These gains are, however, lost because of poor retention in care and viral suppression rates and therefore required urgent attention.
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Affiliation(s)
- Vidya Kalawan
- Department of Paediatrics and Children Health, University of KwaZulu-Natal, Durban, South Africa.,King Dinizulu Hospital, Durban, South Africa
| | - Kevindra Naidoo
- Maternal Adolescent and Child Health (MatCH), University of the Witwatersrand, Johannesburg, South Africa
| | - Moherndran Archary
- Department of Paediatrics and Children Health, University of KwaZulu-Natal, Durban, South Africa.,King Edward VIII Hospital, Durban, South Africa
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Vieira L, Mahumane AM, Napua M, Chale F, Manuel JL, Cowan JG, Sherr K, Chapman RR, Pfeiffer JT. HIV-exposed infant follow-up in Mozambique: formative research findings for the design of a cluster randomized controlled trial to improve testing and ART initiation. BMC Health Serv Res 2020; 20:226. [PMID: 32183779 PMCID: PMC7079378 DOI: 10.1186/s12913-020-5051-8] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/05/2019] [Accepted: 02/27/2020] [Indexed: 11/10/2022] Open
Abstract
BACKGROUND Early infant diagnosis (EID) of HIV-exposed and initiation of HIV-positive infants on anti-retroviral therapy (ART) requires a well-coordinated cascade of care. Loss-to-follow-up (LTFU) can occur at multiple steps and effective EID is impeded by human resource constraints, difficulty with patient tracking, and long waiting periods. The objective of this research was to conduct formative research to guide the development of an intervention to improve the pediatric HIV care cascade in central Mozambique. The study was conducted in Manica and Sofala Provinces where the adult HIV burden is higher than the national average. The research focused on 3 large clinics in each province, along the highly populated Beira corridor. METHODS The research was conducted in 2014 over 3 months at six facilities and consisted of 1) patient flow mapping and collection of health systems data from postpartum, child-at-risk, and ART service registries, 2) measurement of clinic waiting times, and 3) patient and health worker focus groups. RESULTS HIV testing and ART initiation coverage for mothers tends to be high, but EID and pediatric ART initiation are hampered by lack of patient tracking, long waiting times, and inadequate counseling to navigate the care cascade. About 76% of HIV-positive infants were LTFU and did not initiate ART. CONCLUSIONS Effective interventions to reduce LTFU in EID and improve pediatric ART initiation should focus on patient tracking, active follow-up of defaulting patients, reduction in EID turn-around times for PCR results, and initiation of ART by nurses in child-at-risk services. TRIAL REGISTRATION Retrospectively registered, ISRCTN67747315, July 24, 2019.
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Affiliation(s)
- Lúcia Vieira
- Ministry of Health, Centro de Investigação Operacional da Beira, Institute Nacional de Saúde, 1323 Correia de Brito Street, Ponta-gêa Health Center Building, Beira, Sofala, Mozambique.
| | - Arlete Miloque Mahumane
- Ministry of Health, Centro de Investigação Operacional da Beira, Institute Nacional de Saúde, 1323 Correia de Brito Street, Ponta-gêa Health Center Building, Beira, Sofala, Mozambique
| | - Manuel Napua
- Ministry of Health, Centro de Investigação Operacional da Beira, Institute Nacional de Saúde, 1323 Correia de Brito Street, Ponta-gêa Health Center Building, Beira, Sofala, Mozambique
| | - Falume Chale
- Ministry of Health, Centro de Investigação Operacional da Beira, Institute Nacional de Saúde, 1323 Correia de Brito Street, Ponta-gêa Health Center Building, Beira, Sofala, Mozambique
| | - João Luís Manuel
- Ministry of Health, Centro de Investigação Operacional da Beira, Institute Nacional de Saúde, 1323 Correia de Brito Street, Ponta-gêa Health Center Building, Beira, Sofala, Mozambique
| | - Jessica Greenberg Cowan
- School of Nursing, University of Washington, Seattle, USA
- Department of Family Medicine, University of Washington, Seattle, USA
| | - Kenneth Sherr
- School of Nursing, University of Washington, Seattle, USA
- Health Alliance International, Beira, Mozambique
| | - Rachel R Chapman
- Department of Anthropology, University of Washington, Seattle, USA
| | - James T Pfeiffer
- School of Nursing, University of Washington, Seattle, USA
- Health Alliance International, Beira, Mozambique
- Department of Anthropology, University of Washington, Seattle, USA
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Zhan L, Granade T, Liu Y, Wei X, Youngpairoj A, Sullivan V, Johnson J, Bischof J. Development and optimization of thermal contrast amplification lateral flow immunoassays for ultrasensitive HIV p24 protein detection. MICROSYSTEMS & NANOENGINEERING 2020; 6:54. [PMID: 34567665 PMCID: PMC8433161 DOI: 10.1038/s41378-020-0168-9] [Citation(s) in RCA: 28] [Impact Index Per Article: 5.6] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 01/03/2020] [Revised: 03/24/2020] [Accepted: 04/10/2020] [Indexed: 05/06/2023]
Abstract
Detection of human immunodeficiency virus (HIV) p24 protein at a single pg/ml concentration in point-of-care (POC) settings is important because it can facilitate acute HIV infection diagnosis with a detection sensitivity approaching that of laboratory-based assays. However, the limit of detection (LOD) of lateral flow immunoassays (LFAs), the most prominent POC diagnostic platform, falls short of that of laboratory protein detection methods such as enzyme-linked immunosorbent assay (ELISA). Here, we report the development and optimization of a thermal contrast amplification (TCA) LFA that will allow ultrasensitive detection of 8 pg/ml p24 protein spiked into human serum at POC, approaching the LOD of a laboratory test. To achieve this aim, we pursued several innovations as follows: (a) defining a new quantitative figure of merit for LFA design based on the specific to nonspecific binding ratio (BR); (b) using different sizes and shapes of gold nanoparticles (GNPs) in the systematic optimization of TCA LFA designs; and (c) exploring new laser wavelengths and power regimes for TCA LFA designs. First, we optimized the blocking buffer for the membrane and running buffer by quantitatively measuring the BR using a TCA reader. The TCA reader interprets the thermal signal (i.e., temperature) of GNPs within the membrane when irradiated by a laser at the plasmon resonance wavelength of the particle. This process results in higher detection and quantitation of GNPs than in traditional visual detection (i.e., color intensity). Further, we investigated the effect of laser power (30, 100, 200 mW), GNP size and shape (30 and 100 nm gold spheres, 150 nm gold-silica shells), and laser wavelength (532, 800 nm). Applying these innovations to a new TCA LFA design, we demonstrated that 100 nm spheres with a 100 mW 532 nm laser provided the best performance (i.e., LOD = 8 pg/ml). This LOD is significantly better than that of the current colorimetric LFA and is in the range of the laboratory-based p24 ELISA. In summary, this TCA LFA for p24 protein shows promise for detecting acute HIV infection in POC settings.
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Affiliation(s)
- Li Zhan
- Department of Mechanical Engineering, University of Minnesota, Minneapolis, MN USA
| | | | - Yilin Liu
- Department of Mechanical Engineering, University of Minnesota, Minneapolis, MN USA
| | - Xierong Wei
- Centers for Disease Control and Prevention, Atlanta, GA USA
| | - Ae Youngpairoj
- Centers for Disease Control and Prevention, Atlanta, GA USA
| | | | - Jeff Johnson
- Centers for Disease Control and Prevention, Atlanta, GA USA
| | - John Bischof
- Department of Mechanical Engineering, University of Minnesota, Minneapolis, MN USA
- Department of Biomedical Engineering, University of Minnesota, Minneapolis, MN USA
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Dakum P, Tola M, Iboro N, Okolo CA, Anuforom O, Chime C, Peters S, Jumare J, Ogbanufe O, Ahmad A, Ndembi N. Correlates and determinants of Early Infant Diagnosis outcomes in North-Central Nigeria. AIDS Res Ther 2019; 16:27. [PMID: 31521170 PMCID: PMC6744629 DOI: 10.1186/s12981-019-0245-z] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/27/2019] [Accepted: 08/30/2019] [Indexed: 11/10/2022] Open
Abstract
BACKGROUND A negative status following confirmatory Early Infant Diagnosis (EID) is the desired pediatric outcome of prevention of Mother to Child Transmission (PMTCT) programs. EID impacts epidemic control by confirming non-infected HIV-exposed infants (HEIs) and prompting timely initiation of ART in HIV-infected babies which improves treatment outcomes. OBJECTIVES We explored factors associated with EID outcomes among HEI in North-Central Nigeria. METHOD This is a cross-sectional study using EID data of PMTCT-enrollees matched with results of HEI's dried blood samples (DBS), processed for DNA-PCR from January 2015 through July 2017. Statistical analyses were done using SPSS version 20.0 to generate frequencies and examine associations, including binomial logistic regression with p < 0.05 being statistically significant. RESULTS Of 14,448 HEI in this analysis, 51.8% were female and 95% (n = 12,801) were breastfed. The median age of the infants at sample collection was 8 weeks (IQR 6-20), compared to HEI tested after 20 weeks of age, those tested earlier had significantly greater odds of a negative HIV result (≤ 6 weeks: OR = 3.8; 6-8 weeks: OR = 2.1; 8-20 weeks: OR = 1.5) with evidence of a significant linear trend (p < 0.001). Similarly, HEI whose mothers received combination antiretroviral therapy (cART) before (OR = 11.8) or during the index pregnancy (OR = 8.4) had significantly higher odds as compared to those whose mothers did not receive cART. In addition, HEI not breastfed had greater odds of negative HIV result as compared to those breastfed (OR = 1.9). CONCLUSIONS cART prior to and during pregnancy, earlier age of HEI at EID testing and alternative feeding other than breastfeeding were associated with an increased likelihood of being HIV-negative on EID. Therefore, strategies to scale-up PMTCT services are needed to mitigate the burden of HIV among children.
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Njuguna IN, Cranmer LM, Wagner AD, LaCourse SM, Mugo C, Benki-Nugent S, Richardson BA, Stern J, Maleche-Obimbo E, Wamalwa DC, John-Stewart G. Brief Report: Cofactors of Mortality Among Hospitalized HIV-Infected Children Initiating Antiretroviral Therapy in Kenya. J Acquir Immune Defic Syndr 2019; 81:138-144. [PMID: 31095004 PMCID: PMC6609091 DOI: 10.1097/qai.0000000000002012] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
Abstract
OBJECTIVES Identifying factors associated with mortality among acutely ill HIV-infected children presenting with advanced HIV disease may help clinicians optimize care for those at highest risk of death. DESIGN Using data from a randomized controlled trial (NCT02063880), we determined baseline sociodemographic, clinical, and laboratory cofactors of mortality among HIV-infected children in Kenya. METHODS We enrolled hospitalized, HIV-infected, antiretroviral therapy-naive children (0-12 years), initiated antiretroviral therapy, and followed up them for 6 months. We used Cox proportional hazards regression to estimate hazard ratios (HRs) for death and 95% confidence intervals (CIs). RESULTS Of 181 enrolled children, 39 (22%) died. Common diagnoses at death were pneumonia or suspected pulmonary tuberculosis [23 (59%)] and gastroenteritis [7 (18%)]. Factors associated with mortality in univariate analysis included age <2 years [HR 3.08 (95% CI: 1.50 to 6.33)], orphaned or vulnerable child (OVC) [HR 2.05 (95% CI: 1.09 to 3.84)], weight-for-age Z score <-2 [HR 2.29 (95% CI: 1.05 to 5.00)], diagnosis of pneumonia with hypoxia [HR 5.25 (95% CI: 2.00 to 13.84)], oral thrush [HR 2.17 (95% CI: 1.15 to 4.09)], persistent diarrhea [HR 3.81 (95% CI: 1.89 to 7.69)], and higher log10 HIV-1 viral load [HR 2.16 (95% CI: 1.35 to 3.46)] (all P < 0.05). In multivariable analysis, age <2 years and OVC status remained significantly associated with mortality. CONCLUSIONS Young age and OVC status independently predicted mortality. Hypoxic pneumonia, oral thrush, and persistent diarrhea are important clinical features that predict mortality. Strategies to enhance early diagnosis in children and improve hospital management of critically ill HIV-infected children are needed.
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Affiliation(s)
- Irene N Njuguna
- Kenyatta National Hospital, Nairobi, Kenya
- Department of Epidemiology, University of Washington, Seattle, WA
| | - Lisa M Cranmer
- Department of Pediatrics, Emory University School of Medicine and Children's Healthcare of Atlanta, Atlanta, GA
| | | | | | - Cyrus Mugo
- Department of Pediatrics and Child Health, University of Nairobi, Nairobi, Kenya
| | | | | | | | | | - Dalton C Wamalwa
- Department of Pediatrics and Child Health, University of Nairobi, Nairobi, Kenya
| | - Grace John-Stewart
- Department of Epidemiology, University of Washington, Seattle, WA
- Medicine, University of Washington, Seattle, WA
- Pediatrics, University of Washington, Seattle, WA
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Frank SC, Cohn J, Dunning L, Sacks E, Walensky RP, Mukherjee S, Dugdale CM, Turunga E, Freedberg KA, Ciaranello AL. Clinical effect and cost-effectiveness of incorporation of point-of-care assays into early infant HIV diagnosis programmes in Zimbabwe: a modelling study. Lancet HIV 2019; 6:e182-e190. [PMID: 30737187 PMCID: PMC6408227 DOI: 10.1016/s2352-3018(18)30328-x] [Citation(s) in RCA: 36] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/01/2018] [Revised: 11/07/2018] [Accepted: 11/08/2018] [Indexed: 11/18/2022]
Abstract
BACKGROUND New point-of-care (POC) assays for early infant HIV diagnosis are costlier than conventional total nucleic acid assays, but could increase access to testing, shorten time to results, and expedite initiation of antiretroviral therapy. We aimed to assess the clinical benefits and cost-effectiveness of incorporating these POC assays into early infant diagnosis programmes in Zimbabwe. METHODS We used the Cost Effectiveness of Preventing AIDS Complications (CEPAC)-Pediatric model to examine the clinical benefits, costs, and cost-effectiveness of replacing conventional assays for early infant HIV diagnosis with POC assays at age 6 weeks in Zimbabwe. We simulated two strategies for early infant HIV diagnosis: conventional and POC. Modelled assays differed in sensitivity; specificity; time to, and probability of, return of results; and cost. Model outcomes included survival, life expectancy, and mean lifetime per-person treatment cost, which were reported separately for all HIV-exposed infants and all infants with HIV. We calculated incremental cost-effectiveness ratios with discounted (3% per year) costs and life expectancy from a health-care system perspective for all HIV-exposed infants. We judged incremental cost-effectiveness ratios of $1010 (Zimbabwe's annual gross domestic product per person) or less per year of life saved to be cost-effective. FINDINGS When conventional assays were used for early infant diagnosis, projected undiscounted life expectancy was 22·7 years for infants with HIV and 62·5 years for all HIV-exposed infants, at a cost of $610 per HIV-exposed infant. Use of POC assays for early infant HIV diagnosis improved projected undiscounted life expectancy to 25·5 years among infants with HIV and 62·6 years among HIV-exposed infants at a cost of $690 per HIV-exposed infant. At age 12 weeks, survival among all infants with HIV was 76·1% with the conventional testing strategy and 83·5% with the POC testing strategy. The incremental cost-effectiveness ratio of POC assays versus conventional assays for early infant diagnosis was $680 per year of life saved. When conventional assay characteristics remained constant, this ratio remained under the cost-effectiveness threshold as long as the specificity and sensitivity of the POC assay were greater than 92% and 65%, respectively. Our results were robust to plausible variations in POC assay cost, the probability of ART initiation, and probability of return of the results of POC testing. INTERPRETATION Compared with conventional assays, POC assays for early infant HIV diagnosis in Zimbabwe will improve survival, extend life expectancy, and be cost-effective for HIV-exposed infants. FUNDING Elizabeth Glaser Pediatric AIDS Foundation, US National Institute of Allergy and Infectious Diseases, Eunice Kennedy Shriver National Institute of Child Health and Human Development, and Unitaid.
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Affiliation(s)
- Simone C. Frank
- Division of General Internal Medicine, Massachusetts General Hospital, Boston, Massachusetts, United States of America
- Medical Practice Evaluation Center, Department of Medicine, Massachusetts General Hospital, Boston, Massachusetts, United States of America
| | - Jennifer Cohn
- Elizabeth Glaser Pediatric AIDS Foundation, Geneva, Switzerland
- Division of Infectious Disease, University of Pennsylvania, Philadelphia, Pennsylvania, United States of America
| | - Lorna Dunning
- Division of Epidemiology and Biostatistics, School of Public Health & Family Medicine, University of Cape Town, Cape Town, South Africa
| | - Emma Sacks
- Elizabeth Glaser Pediatric AIDS Foundation, Washington, DC, United States of America
| | - Rochelle P. Walensky
- Medical Practice Evaluation Center, Department of Medicine, Massachusetts General Hospital, Boston, Massachusetts, United States of America
- Division of Infectious Diseases, Massachusetts General Hospital, Boston, Massachusetts, United States of America
| | - Sushant Mukherjee
- Elizabeth Glaser Pediatric AIDS Foundation, Washington, DC, United States of America
| | - Caitlin M. Dugdale
- Medical Practice Evaluation Center, Department of Medicine, Massachusetts General Hospital, Boston, Massachusetts, United States of America
- Division of Infectious Diseases, Massachusetts General Hospital, Boston, Massachusetts, United States of America
| | - Esther Turunga
- Elizabeth Glaser Pediatric AIDS Foundation, Geneva, Switzerland
| | - Kenneth A. Freedberg
- Division of General Internal Medicine, Massachusetts General Hospital, Boston, Massachusetts, United States of America
- Medical Practice Evaluation Center, Department of Medicine, Massachusetts General Hospital, Boston, Massachusetts, United States of America
- Division of Infectious Diseases, Massachusetts General Hospital, Boston, Massachusetts, United States of America
| | - Andrea L. Ciaranello
- Medical Practice Evaluation Center, Department of Medicine, Massachusetts General Hospital, Boston, Massachusetts, United States of America
- Division of Infectious Diseases, Massachusetts General Hospital, Boston, Massachusetts, United States of America
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Rapid Serological Tests Ineffectively Screen for HIV Exposure in HIV-Positive Infants. J Acquir Immune Defic Syndr 2019; 77:331-336. [PMID: 29206722 DOI: 10.1097/qai.0000000000001609] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
Abstract
BACKGROUND Data on the performance and utility of rapid serological tests in infants to determine HIV exposure are unclear and in some instances contradictory. This study sought to understand the performance of rapid serological tests in high HIV burden, high Option B+ coverage settings to be used as an HIV exposure screening tool. METHODS A total of 3600 infants up to 24 months of age at 4 regional hospitals in Uganda were systematically enrolled and tested simultaneously using both HIV rapid serological and nucleic acid-based tests. RESULTS Only 58 of the 94 HIV-positive infants who received both rapid serological and nucleic acid-based tests were positive with the rapid serological test (sensitivity: 61.7%; 95% confidence interval: 51.1 to 71.5). Using rapid serological tests to screen infants for exposure to HIV and follow-up nucleic acid-based testing would have missed 38.3% (36 of 94) of HIV-positive infants. Finally, several HIV-positive infants who were negative by rapid serological test presented to well-child entry points and were considered healthy. All 3 HIV-positive infants presenting to outreach and immunization were negative by rapid serological testing and 73% (8 of 11) presenting to outpatient. CONCLUSIONS These data suggest that the use of rapid serological tests may have inadequate performance as an indicator of exposure and potential HIV infection among infants presenting at both well-child (immunization and community outreach) and sick-infant (nutrition and inpatient) entry points. To improve the identification of HIV-positive infants, nucleic acid-based testing should instead be considered in infants aged younger than 18 months.
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Sandbulte MR, Gautney BJ, Maloba M, Wexler C, Brown M, Mabachi N, Goggin K, Lwembe R, Nazir N, Odeny TA, Finocchario-Kessler S. Infant HIV testing at birth using point-of-care and conventional HIV DNA PCR: an implementation feasibility pilot study in Kenya. Pilot Feasibility Stud 2019; 5:18. [PMID: 30701079 PMCID: PMC6347792 DOI: 10.1186/s40814-019-0402-0] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/18/2018] [Accepted: 01/11/2019] [Indexed: 12/03/2022] Open
Abstract
Background Infant HIV diagnosis by HIV DNA polymerase chain reaction (PCR) testing at the standard 6 weeks of age is often late to mitigate the mortality peak that occurs in HIV positive infants’ first 2–3 months of life. Kenya recently revised their early infant diagnosis (EID) guidelines to include HIV DNA PCR testing at birth (pilot only), 6 weeks, 6 months, and 12 months postnatal and a final 18-month antibody test. The World Health Organization (WHO) approved point-of-care (POC) diagnostic platforms for infant HIV testing in resource-limited countries that could simplify logistics and expedite infant diagnosis. Sustainable scale-up and optimal utility in Kenya and other high-prevalence countries depend on robust implementation studies in diverse clinical settings. Methods We will pilot the implementation of birth testing by HIV DNA PCR, as well as two POC testing systems (Xpert HIV-1 Qual [Xpert] and Alere q HIV-1/2 Detect [Alere q]), on specimens collected from Kenyan infants at birth (0 to 2 weeks) and 6 weeks (4 to < 24 weeks) postnatal. The formative phase will inform optimal implementation of birth testing and two POC testing technologies. Qualitative interviews with stakeholders (providers, parents of HIV-exposed infants, and community members) will assess attitudes, barriers, and recommendations to optimize implementation at their respective sites. A non-blinded pilot study at four Kenyan hospitals (n = 2 Xpert, n = 2 Alere q platforms) will evaluate infant HIV POC testing compared with standard of care HIV DNA PCR testing in both the birth and 6-week windows. Objectives of the pilot are to assess uptake, efficiency, quality, implementation variables, user experiences of birth testing with both POC testing systems or with HIV DNA PCR, and costs. Discussion This study will generate data on the clinical impact and feasibility of adding HIV testing at birth utilizing POC and traditional PCR HIV testing strategies in resource-limited settings. Data from this pilot will inform the optimal implementation of Kenya’s birth testing guidelines and of POC testing systems for the improvement of EID outcomes. Trial registration ClinicalTrials.gov, NCT03435887. Registered 26 February 2018. Electronic supplementary material The online version of this article (10.1186/s40814-019-0402-0) contains supplementary material, which is available to authorized users.
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Affiliation(s)
- Matthew R Sandbulte
- 1Department of Family Medicine, University of Kansas Medical Center, Kansas City, KS USA
| | | | - May Maloba
- Global Health Innovations, Nairobi, Kenya
| | - Catherine Wexler
- 1Department of Family Medicine, University of Kansas Medical Center, Kansas City, KS USA
| | - Melinda Brown
- 1Department of Family Medicine, University of Kansas Medical Center, Kansas City, KS USA
| | - Natabhona Mabachi
- 1Department of Family Medicine, University of Kansas Medical Center, Kansas City, KS USA
| | - Kathy Goggin
- 4Health Services and Outcomes Research, Children's Mercy Hospitals and Clinics, Kansas City, MO USA.,5University of Missouri-Kansas City School of Medicine, Kansas City, MO USA
| | - Raphael Lwembe
- 6Centre for Virus Research, Kenya Medical Research Institute, Nairobi, Kenya
| | - Niaman Nazir
- 7Department of Preventive Medicine and Public Health, University of Kansas Medical Center, Kansas City, KS USA
| | - Thomas A Odeny
- 5University of Missouri-Kansas City School of Medicine, Kansas City, MO USA.,8Center for Microbiology Research, Kenya Medical Research Institute, Nairobi, Kenya
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Yotebieng M, Brazier E, Addison D, Kimmel AD, Cornell M, Keiser O, Parcesepe AM, Onovo A, Lancaster KE, Castelnuovo B, Murnane PM, Cohen CR, Vreeman RC, Davies M, Duda SN, Yiannoutsos CT, Bono RS, Agler R, Bernard C, Syvertsen JL, Sinayobye JD, Wikramanayake R, Sohn AH, von Groote PM, Wandeler G, Leroy V, Williams CF, Wools‐Kaloustian K, Nash D. Research priorities to inform "Treat All" policy implementation for people living with HIV in sub-Saharan Africa: a consensus statement from the International epidemiology Databases to Evaluate AIDS (IeDEA). J Int AIDS Soc 2019; 22:e25218. [PMID: 30657644 PMCID: PMC6338103 DOI: 10.1002/jia2.25218] [Citation(s) in RCA: 25] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/03/2018] [Accepted: 11/07/2018] [Indexed: 12/14/2022] Open
Abstract
INTRODUCTION "Treat All" - the treatment of all people with HIV, irrespective of disease stage or CD4 cell count - represents a paradigm shift in HIV care that has the potential to end AIDS as a public health threat. With accelerating implementation of Treat All in sub-Saharan Africa (SSA), there is a need for a focused agenda and research to identify and inform strategies for promoting timely uptake of HIV treatment, retention in care, and sustained viral suppression and addressing bottlenecks impeding implementation. METHODS The Delphi approach was used to develop consensus around research priorities for Treat All implementation in SSA. Through an iterative process (June 2017 to March 2018), a set of research priorities was collectively formulated and refined by a technical working group and shared for review, deliberation and prioritization by more than 200 researchers, implementation experts, policy/decision-makers, and HIV community representatives in East, Central, Southern and West Africa. RESULTS AND DISCUSSION The process resulted in a list of nine research priorities for generating evidence to guide Treat All policies, implementation strategies and monitoring efforts. These priorities highlight the need for increased focus on adolescents, men, and those with mental health and substance use disorders - groups that remain underserved in SSA and for whom more effective testing, linkage and care strategies need to be identified. The priorities also reflect consensus on the need to: (1) generate accurate national and sub-national estimates of the size of key populations and describe those who remain underserved along the HIV-care continuum; (2) characterize the timeliness of HIV care and short- and long-term HIV care continuum outcomes, as well as factors influencing timely achievement of these outcomes; (3) estimate the incidence and prevalence of HIV-drug resistance and regimen switching; and (4) identify cost-effective and affordable service delivery models and strategies to optimize uptake and minimize gaps, disparities, and losses along the HIV-care continuum, particularly among underserved populations. CONCLUSIONS Reflecting consensus among a broad group of experts, researchers, policy- and decision-makers, PLWH, and other stakeholders, the resulting research priorities highlight important evidence gaps that are relevant for ministries of health, funders, normative bodies and research networks.
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Affiliation(s)
| | - Ellen Brazier
- Institute for Implementation Science in Population HealthCity University of New YorkNew YorkNYUSA
- Department of Epidemiology and BiostatisticsGraduate School of Public Health and Health PolicyCity University of New YorkNew YorkNYUSA
| | - Diane Addison
- Institute for Implementation Science in Population HealthCity University of New YorkNew YorkNYUSA
- Department of Epidemiology and BiostatisticsGraduate School of Public Health and Health PolicyCity University of New YorkNew YorkNYUSA
| | - April D Kimmel
- Department of Health Behavior and PolicyVirginia Commonwealth University School of MedicineRichmondVAUSA
| | - Morna Cornell
- Centre for Infectious Disease Epidemiology& ResearchSchool of Public Health & Family MedicineUniversity of Cape TownCape TownSouth Africa
| | - Olivia Keiser
- Institute of Global HealthUniversity of GenevaGenevaSwitzerland
| | | | - Amobi Onovo
- University of North Carolina at Chapel HillChapel HillNCUSA
| | | | | | - Pamela M Murnane
- Center for AIDS Prevention StudiesDepartment of MedicineUniversity of California San FranciscoSan FranciscoCAUSA
| | - Craig R Cohen
- Department of Obstetrics, Gynecology & Reproductive SciencesBixby Center for Global Reproductive HealthUniversity of California San FranciscoSan FranciscoCAUSA
| | - Rachel C Vreeman
- Department of PediatricsIndiana University School of MedicineIndianapolisINUSA
| | - Mary‐Ann Davies
- School of Public Health and Family MedicineFaculty of Health SciencesUniversity of Cape TownCape TownSouth Africa
| | | | | | - Rose S Bono
- Department of Health Behavior and PolicyVirginia Commonwealth University School of MedicineRichmondVAUSA
| | | | - Charlotte Bernard
- InsermCentre INSERM U1219‐Epidémiologie‐BiostatistiqueSchool of Public Health (ISPED)University of BordeauxBordeauxFrance
| | | | | | - Radhika Wikramanayake
- Institute for Implementation Science in Population HealthCity University of New YorkNew YorkNYUSA
- Department of Epidemiology and BiostatisticsGraduate School of Public Health and Health PolicyCity University of New YorkNew YorkNYUSA
| | - Annette H Sohn
- TREAT AsiaamfAR – The Foundation for AIDS ResearchBangkokThailand
| | - Per M von Groote
- Institute of Social and Preventive Medicine (ISPM)University of BernBernSwitzerland
| | - Gilles Wandeler
- Institute of Social and Preventive Medicine (ISPM)University of BernBernSwitzerland
| | - Valeriane Leroy
- Inserm (French Institute of Health and Medical Research)UMR 1027 Université Toulouse 3ToulouseFrance
| | - Carolyn F Williams
- Epidemiology BranchDivision of AIDS at National Institute of Allergy and Infectious Diseases (NIAID)National Institute of Health (NIH)RockvilleMDUSA
| | | | - Denis Nash
- Institute for Implementation Science in Population HealthCity University of New YorkNew YorkNYUSA
- Department of Epidemiology and BiostatisticsGraduate School of Public Health and Health PolicyCity University of New YorkNew YorkNYUSA
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Opollo VS, Nikuze A, Ben-Farhat J, Anyango E, Humwa F, Oyaro B, Wanjala S, Omwoyo W, Majiwa M, Akelo V, Zeh C, Maman D. Field evaluation of near point of care Cepheid GeneXpert HIV-1 Qual for early infant diagnosis. PLoS One 2018; 13:e0209778. [PMID: 30589900 PMCID: PMC6307732 DOI: 10.1371/journal.pone.0209778] [Citation(s) in RCA: 18] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/16/2018] [Accepted: 12/11/2018] [Indexed: 11/18/2022] Open
Abstract
Background Access to point-of-care HIV testing shortens turn-around times, time to diagnosis and reduces loss to follow-up hence minimizing barriers to early linkage to care and treatment among HIV infected infants. Currently samples for early infant HIV diagnosis are sent to centralized testing facilities which are few and located only at specific regions in Kenya. However, there are Point of Care (POC) early infant diagnosis [EID] technologies elsewhere such as SAMBA and ALERE-Q that are yet to be evaluated in Kenya despite the urgent need for data to inform policy formulation regarding EID. The Cepheid GeneXpert HIV-1 Qual (GeneXpert) technology for POC EID offers a great opportunity to minimize HIV associated morbidity, mortality and loss to follow-up through decentralization of early infant HIV testing to the clinics. This technology also allows for same-day results thus facilitating prompt linkage to care. Methods We evaluated the GeneXpert HIV Qual EID POC in Homabay County against the standard of care platform, Roche CAP/CTM HIV-1 qualitative PCR, using dried blood spots (DBS). Between February—July 2016, DBS samples were collected from HIV exposed children <18 months of age enrolled in a cross-sectional study. Samples were collected by qualified nurse counselors, and were tested by trained technicians using field based GeneXpert and conventional laboratory based Roche CAP/CTM HIV-1 qualitative PCR. Sensitivity and specificity were determined. Results Overall, 3,814 mother/infant pairs were included in the study, out of which 921 infants were HIV exposed as per the mothers’ HIV status and based on the infant’s HIV rapid test. A total of 969 PCR tests were performed, out of which 30 (3.3%) infants were concordantly positive using both platforms. GeneXpert HIV-1 Qual yielded a sensitivity of 94.1% and specificity of 99.8% with an overall error rate of 0.7%. Conclusion Our findings show that GeneXpert HIV-1 Qual performs well compared to CAP/CTM using DBS samples, suggesting that this technology may be adopted in decentralized laboratories as a near POC device. It may contribute to prompt diagnosis of HIV exposed infants hence enabling early linkage to care, thus advancing further gains in EID.
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Affiliation(s)
- Valarie Sarah Opollo
- Kenya Medical Research Institute/Centre for Global Health Research, Kisumu, Kenya
- * E-mail:
| | | | | | - Emily Anyango
- Kenya Medical Research Institute/Centre for Global Health Research, Kisumu, Kenya
| | - Felix Humwa
- Kenya Medical Research Institute/Centre for Global Health Research, Kisumu, Kenya
| | - Boaz Oyaro
- Kenya Medical Research Institute/Centre for Global Health Research, Kisumu, Kenya
| | | | | | - Maxwel Majiwa
- Kenya Medical Research Institute/Centre for Global Health Research, Kisumu, Kenya
| | - Victor Akelo
- Kenya Medical Research Institute/Centre for Global Health Research, Kisumu, Kenya
| | - Clement Zeh
- U.S. Centers for Disease Control and Prevention, Clinical Research Center, Kisumu, Kenya
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Ochodo EA, Kakourou A, Mallett S, Deeks JJ. Point-of-care tests detecting HIV nucleic acids for diagnosis of HIV infection in infants and children aged 18 months or less. Hippokratia 2018. [DOI: 10.1002/14651858.cd013207] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/05/2022]
Affiliation(s)
- Eleanor A Ochodo
- Stellenbosch University; Centre for Evidence-based Health Care, Faculty of Medicine and Health Sciences; PO Box 241 Cape Town South Africa 8000
| | - Artemisia Kakourou
- University of Ioannina School of Medicine; Department of Hygiene and Epidemiology; Ioannina University Campus Ioannina Greece
| | - Sue Mallett
- University of Birmingham; Institute of Applied Health Research; Edgbaston Birmingham UK B15 2TT
| | - Jonathan J Deeks
- University of Birmingham; Institute of Applied Health Research; Edgbaston Birmingham UK B15 2TT
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Oleribe OO, Enenche E, Udofia D, Ekom E, Osita-Oleribe PI, Kim JU, Taylor-Robinson SD. Assessment of the effectiveness of PMTCT program in eight service delivery points in North Central Nigeria. HIV AIDS (Auckl) 2018; 10:253-259. [PMID: 30538583 PMCID: PMC6251355 DOI: 10.2147/hiv.s157685] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/23/2022] Open
Abstract
BACKGROUND Mother-to-child transmission (MTCT) of HIV is one of the commonest avenues through which infants are infected with HIV. To achieve an HIV-free generation, MTCT of HIV should be eliminated. Nigeria began prevention of mother-to-child transmission (PMTCT) services 13 years ago, but it still contributes to over one-third of global MTCT burden. We set out to explore and define the effectiveness of PMTCT in selected sites in North Central Nigeria. METHODS We conducted a retrospective secondary data analysis at eight service delivery points in two states. One thousand four hundred and fifty-four mother-infant pair data sets from 2012 to 2016 were extracted and analyzed. Maternal/infant antiretroviral (ARV) services, early infant diagnosis (EID), and final outcomes were reviewed to examine the predictors of MTCT of HIV in these centers. RESULTS We retrieved 1,454 mother-infant pair data sets. While 89.5% (1,302) of positive pregnant women (PPW) and 92.2% (1,340) of HIV-exposed infants (HEIs) received ARV prophylaxis/ARV treatment (ART), 88.4% (1,285) infants were breastfed with 32.5% still receiving breast milk at the time of dry blood spot (DBS) collection. EID PCR positivity rate was 3.5% (range, 0.0%-11.1%). Facility of delivery (χ2=24.99, P<0.00), mother on ARV (χ2=48.8, P<0.00), mother having received ARV prophylaxis (χ2=89.59, P<0.00), infant having received ARV prophylaxis (χ2=58.56, P<0.00), and baby having received cotrimoxazole (χ2=55.24, P<0.00) all significantly prevented positive EID results. However, mode of delivery and breastfeeding were not significantly associated with positive EID results. CONCLUSION This study supports PMTCT services as it minimizes the transfer of HIV from infected mothers to HEIs. To eliminate HIV and achieve zero new HIV infections, every HIV-positive pregnant woman should receive ARV prophylaxis and should be supported postdelivery to prevent transfer of infection to the newborn. Also, HEIs should receive timely ARV and cotrimoxazole prophylaxis.
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Affiliation(s)
| | - Ede Enenche
- Excellence and Friends Management Care Centre (EFMC), Abuja, Nigeria,
| | - Deborah Udofia
- Excellence and Friends Management Care Centre (EFMC), Abuja, Nigeria,
| | - Ekei Ekom
- Excellence and Friends Management Care Centre (EFMC), Abuja, Nigeria,
| | | | - Jin Un Kim
- Hepatology Unit, Imperial College London, London, UK
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Abuogi LL, Humphrey JM, Mpody C, Yotebieng M, Murnane PM, Clouse K, Otieno L, Cohen CR, Wools-Kaloustian K. Achieving UNAIDS 90-90-90 targets for pregnant and postpartum women in sub-Saharan Africa: progress, gaps and research needs. J Virus Erad 2018; 4:33-39. [PMID: 30515312 PMCID: PMC6248851] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/01/2022] Open
Abstract
The implementation of the 2013 World Health Organization Option B+ recommendations for HIV treatment during pregnancy has helped drive significant progress in achieving universal treatment for pregnant and postpartum women in sub-Saharan Africa (SSA). Yet, critical research and implementation gaps exist in achieving the UNAIDS 90-90-90 targets. To help guide researchers, programmers and policymakers in prioritising these areas, we undertook a comprehensive review of the progress, gaps and research needs to achieve the 90-90-90 targets for this population in the Option B+ era, including early infant HIV diagnosis (EID) for HIV-exposed infants. Salient areas where progress has been achieved or where gaps remain include: (1) knowledge of HIV status is higher among people with HIV in southern and eastern Africa compared to western and central Africa (81% versus 48%, UNAIDS); (2) access to antiretroviral therapy (ART) for pregnant women has doubled in 22 of 42 SSA countries, but only six have achieved the second 90, and nearly a quarter of pregnant women initiating ART become lost to follow-up; (3) viral suppression data for this population are sparse (estimates range from 30% to 98% peripartum), with only half of women maintaining suppression through 12 months postpartum; and (4) EID rates range from 15% to 62%, with only three of 21 high-burden SSA countries testing >50% HIV-exposed infants within the first 2 months of life. We have identified and outlined promising innovations and research designed to address these gaps and improve the health of pregnant and postpartum women living with HIV and their infants.
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Affiliation(s)
- Lisa L Abuogi
- Department of Pediatrics, University of Colorado,
Denver, Aurora, CO,
USA,Corresponding author:
Lisa Abuogi, Department of Pediatrics, University of Colorado,
Denver, Aurora,
CO,
USA
| | - John M Humphrey
- Department of Medicine, Indiana University School of Medicine,
Indianapolis, IN,
USA
| | - Christian Mpody
- Division of Epidemiology, Ohio State University,
Columbus, OH,
USA
| | - Marcel Yotebieng
- Division of Epidemiology, Ohio State University,
Columbus, OH,
USA
| | - Pamela M Murnane
- Center for AIDS Prevention Studies, University of California San Francisco,
San Francisco, CA,
USA
| | - Kate Clouse
- Vanderbilt Institute for Global Health, Vanderbilt University,
Nashville, TN,
USA
| | - Lindah Otieno
- Center for Microbial Research, Research Care and Training Program, Kenya Medical Research Institute,
Nairobi,
Kenya
| | - Craig R Cohen
- Department of Obstetrics, Gynecology & Reproductive Sciences,
University of California San Francisco, CA,
USA
| | - Kara Wools-Kaloustian
- Department of Medicine, Indiana University School of Medicine,
Indianapolis, IN,
USA
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Technau KG, Strehlau R, Patel F, Shiau S, Burke M, Conradie M, Sorour G, Sherman GG, Coovadia A, Murnane PM, Abrams EJ, Kuhn L. 12-month outcomes of HIV-infected infants identified at birth at one maternity site in Johannesburg, South Africa: an observational cohort study. Lancet HIV 2018; 5:e706-e714. [PMID: 30416043 DOI: 10.1016/s2352-3018(18)30251-0] [Citation(s) in RCA: 24] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/10/2018] [Revised: 08/20/2018] [Accepted: 09/10/2018] [Indexed: 01/20/2023]
Abstract
BACKGROUND Initiation of antiretroviral therapy (ART) following diagnosis of HIV infection at birth is an emerging area of paediatric HIV care. We present outcomes of HIV-infected infants identified at birth at Rahima Moosa Mother and Child Hospital in Johannesburg, South Africa. METHODS From September, 2013 (era 1), only high-risk HIV-exposed infants were offered diagnostic HIV PCR tests at birth. From June, 2014 (era 2), all HIV-exposed infants were offered laboratory-based diagnostic PCR tests. From October, 2014 (era 3), point of care (POC) diagnostic PCR tests were also done if staff availability allowed. We describe time to ART initiation, mortality, retention in care, and viral suppression among the HIV-infected infants identified across these eras. FINDINGS We tested 5449 HIV-exposed infants who were born between Sept 1, 2013, and June 30, 2016. 88 neonates with confirmed HIV infection were identified and included in the study, of which 86 (98%) started ART. Median age at ART initiation decreased from 9 days (IQR 6-25) in eras 1 and 2 to 2 days (1-8) in era 3. In era 3, more neonates who were co-tested with POC testing started ART within 48 h of birth (29 [83%] of 35; median 1 day [IQR 1-2]) than infants who were not co-tested (one [4%] of 29; median 6 days [5-10]). The probability of mortality by 12 months across the eras was 14% (95% CI 8-24) and did not differ by era. Of the 72 infants who survived and initiated ART at the site, 56 (78%) were retained at 12 months. Of the 56 infants retained in care, 40 (71%) had a viral load less than 400 copies per mL at 12 months, with no differences between eras (p=0·23). INTERPRETATION HIV-infected infants can be identified at birth and ART can be initiated within hours to days. Although most infants in our cohort started ART, mortality remained unacceptably high with suboptimal retention and viral suppression. Reducing mortality and improving retention and viral suppression remain urgent priorities. FUNDING Eunice Kennedy Shriver National Institute of Child Health and Human Development/National Institute of Allergy and Infectious Disease, National Institutes of Health, USAID/PEPfAR, and the South African National HIV Programme.
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Affiliation(s)
- Karl-Günter Technau
- Empilweni Services and Research Unit, Department of Paediatrics and Child Health, Rahima Moosa Mother and Child Hospital, Faculty of Health Sciences, University of the Witwatersrand, South Africa
| | - Renate Strehlau
- Empilweni Services and Research Unit, Department of Paediatrics and Child Health, Rahima Moosa Mother and Child Hospital, Faculty of Health Sciences, University of the Witwatersrand, South Africa
| | - Faeezah Patel
- Empilweni Services and Research Unit, Department of Paediatrics and Child Health, Rahima Moosa Mother and Child Hospital, Faculty of Health Sciences, University of the Witwatersrand, South Africa
| | - Stephanie Shiau
- Empilweni Services and Research Unit, Department of Paediatrics and Child Health, Rahima Moosa Mother and Child Hospital, Faculty of Health Sciences, University of the Witwatersrand, South Africa
| | - Megan Burke
- Empilweni Services and Research Unit, Department of Paediatrics and Child Health, Rahima Moosa Mother and Child Hospital, Faculty of Health Sciences, University of the Witwatersrand, South Africa
| | - Martie Conradie
- Empilweni Services and Research Unit, Department of Paediatrics and Child Health, Rahima Moosa Mother and Child Hospital, Faculty of Health Sciences, University of the Witwatersrand, South Africa
| | - Gillian Sorour
- Empilweni Services and Research Unit, Department of Paediatrics and Child Health, Rahima Moosa Mother and Child Hospital, Faculty of Health Sciences, University of the Witwatersrand, South Africa
| | - Gayle G Sherman
- Empilweni Services and Research Unit, Department of Paediatrics and Child Health, Rahima Moosa Mother and Child Hospital, Faculty of Health Sciences, University of the Witwatersrand, South Africa; Centre for HIV and Sexually Transmitted Infections, National Institute for Communicable Diseases, Johannesburg, South Africa
| | - Ashraf Coovadia
- Empilweni Services and Research Unit, Department of Paediatrics and Child Health, Rahima Moosa Mother and Child Hospital, Faculty of Health Sciences, University of the Witwatersrand, South Africa
| | - Pamela M Murnane
- Empilweni Services and Research Unit, Department of Paediatrics and Child Health, Rahima Moosa Mother and Child Hospital, Faculty of Health Sciences, University of the Witwatersrand, South Africa; Gertrude H Sergievsky Center, College of Physicians and Surgeons, and Department of Epidemiology, Mailman School of Public Health, Columbia University, New York, NY, USA; Center for AIDS Prevention Studies, Department of Medicine, University of California San Francisco, CA, USA
| | - Elaine J Abrams
- Empilweni Services and Research Unit, Department of Paediatrics and Child Health, Rahima Moosa Mother and Child Hospital, Faculty of Health Sciences, University of the Witwatersrand, South Africa; ICAP at Columbia, Mailman School of Public Health, and Department of Pediatrics, College of Physicians and Surgeons, Columbia University, New York, NY, USA
| | - Louise Kuhn
- Empilweni Services and Research Unit, Department of Paediatrics and Child Health, Rahima Moosa Mother and Child Hospital, Faculty of Health Sciences, University of the Witwatersrand, South Africa; Gertrude H Sergievsky Center, College of Physicians and Surgeons, and Department of Epidemiology, Mailman School of Public Health, Columbia University, New York, NY, USA.
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Achieving UNAIDS 90-90-90 targets for pregnant and postpartum women in sub-Saharan Africa: progress, gaps and research needs. J Virus Erad 2018. [DOI: 10.1016/s2055-6640(20)30343-5] [Citation(s) in RCA: 33] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/19/2022] Open
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Gray ER, Bain R, Varsaneux O, Peeling RW, Stevens MM, McKendry RA. p24 revisited: a landscape review of antigen detection for early HIV diagnosis. AIDS 2018; 32:2089-2102. [PMID: 30102659 PMCID: PMC6139023 DOI: 10.1097/qad.0000000000001982] [Citation(s) in RCA: 35] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/05/2023]
Abstract
: Despite major advances in HIV testing, early detection of infection at the point of care (PoC) remains a key challenge. Although rapid antibody PoC and laboratory-based nucleic acid amplification tests dominate the diagnostics market, the viral capsid protein p24 is recognized as an alternative early virological biomarker of infection. However, the detection of ultra-low levels of p24 at the PoC has proven challenging. Here we review the landscape of p24 diagnostics to identify knowledge gaps and barriers and help shape future research agendas. Five hundred and seventy-four research articles to May 2018 that propose or evaluate diagnostic assays for p24 were identified and reviewed. We give a brief history of diagnostic development, and the utility of p24 as a biomarker in different populations such as infants, the newly infected, those on preexposure prophylaxis and self-testers. We review the performance of commercial p24 assays and consider elements such as immune complex disruption, resource-poor settings, prevalence, and assay antibodies. Emerging and ultrasensitive assays are reviewed and show a number of promising approaches but further translation has been limited. We summarize studies on the health economic benefits of using antigen testing. Finally, we speculate on the future uses of high-performance p24 assays, particularly, if available in self-test format.
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Affiliation(s)
- Eleanor R Gray
- London Centre for Nanotechnology, Faculty of Maths and Physical Sciences, University College London
| | - Robert Bain
- Department of Materials, Department of Bioengineering and Institute of Biomedical Engineering, Imperial College London
| | | | | | - Molly M Stevens
- Department of Materials, Department of Bioengineering and Institute of Biomedical Engineering, Imperial College London
| | - Rachel A McKendry
- London Centre for Nanotechnology, Faculty of Maths and Physical Sciences, University College London
- Division of Medicine, University College London, London, UK
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Kigen HT, Galgalo T, Githuku J, Odhiambo J, Lowther S, Langat B, Wamicwe J, Too R, Gura Z. Predictors of loss to follow up among HIV-exposed children within the prevention of mother to child transmission cascade, Kericho County, Kenya, 2016. Pan Afr Med J 2018; 30:178. [PMID: 30455807 PMCID: PMC6235513 DOI: 10.11604/pamj.2018.30.178.15837] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/19/2018] [Accepted: 05/21/2018] [Indexed: 12/31/2022] Open
Abstract
INTRODUCTION HIV-exposed infants (HEI) lost-to-follow-up (LTFU) remains a problem in sub Saharan Africa (SSA). In 2015, SSA accounted >90% of the 150,000 new infant HIV infections, with an estimated 13,000 reported in Kenya. Despite proven and effective HIV interventions, many HEI fail to benefit because of LTFU. LTFU leads to delays or no initiation of interventions, thereby contributing to significant child morbidity and mortality. Kenya did not achieve the <5% mother-to-child HIV transmission target by 2015 because of problems such as LTFU. We sought to investigate factors associated with LTFU of HEI in Kericho County, Kenya. METHODS A case-control study was conducted in June 2016 employing 1:2 frequency matching by age and hospital of birth. We recruited HEI from HEI birth cohort registers from hospitals for the months of September 2014 through February 2016. Cases were infant-mother pairs that missed their 3-month clinic appointments while controls were those that adhered to their 3-month follow-up visits. Consent was obtained from caregivers and a structured questionnaire was administered. We used chi-square and Fisher's Exact tests to compare groups, calculated odds ratios (OR) and 95% confidence intervals (CI), and performed logistic regression to identify independent risk factors. RESULTS We enrolled 44 cases and 88 controls aged ≥3 to 18 months: Cases ranged from 7.3-17.8 months old and controls from 6.8-17.2 months old. LTFU cases' caregivers were more likely than controls' caregivers to fear knowing HEI status (aOR= 12.71 [CI 3.21-50.23]), lack knowledge that HEI are followed for 18 months (aOR= 12.01 [CI 2.92-48.83]), avoid partners knowing their HEI status(OR= 11.32 [CI 2.92-44.04]), and use traditional medicine (aOR= 6.42 [CI 1.81-22.91]).Factors that were protective of LTFU included mothers knowing their pre-pregnancy HIV status (aOR= 0.23 [CI 0.05-0.71]) and having household health insurance (aOR= 0.11 [CI 0.01-0.76]). CONCLUSION Caregivers' intrinsic, interpersonal, community and health system factors remain crucial towards reducing HEI LTFU. Early HIV testing among mothers, disclosure support, health education, and partner involvement is advocated. Encouraging households to enroll in health insurance could be beneficial. Further studies on the magnitude and the reasons for use of home treatments among caregiver are recommended.
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Affiliation(s)
- Hudson Taabukk Kigen
- Field Epidemiology and Laboratory Training Program (FELTP), Ministry of Health, Nairobi, Kenya
- County Government of Kericho, Department of Health, Kericho, Kenya
| | - Tura Galgalo
- US Centers for Diseases Prevention and Control (CDC), Division of Global Health Protection (DGHP), Kenya
| | - Jane Githuku
- Field Epidemiology and Laboratory Training Program (FELTP), Ministry of Health, Nairobi, Kenya
| | - Jacob Odhiambo
- National AIDS and STI Control Program (NASCOP), Ministry of Health, Kenya
| | - Sara Lowther
- US Centers for Diseases Prevention and Control (CDC), Division of Global Health Protection (DGHP), Kenya
| | - Betty Langat
- County Government of Kericho, Department of Health, Kericho, Kenya
| | - Joyce Wamicwe
- National AIDS and STI Control Program (NASCOP), Ministry of Health, Kenya
| | - Robert Too
- Moi University, School of Public Health, Eldoret, Kenya
| | - Zeinab Gura
- Field Epidemiology and Laboratory Training Program (FELTP), Ministry of Health, Nairobi, Kenya
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Bwana VM, Mfinanga SG, Simulundu E, Mboera LEG, Michelo C. Accessibility of Early Infant Diagnostic Services by Under-5 Years and HIV Exposed Children in Muheza District, North-East Tanzania. Front Public Health 2018; 6:139. [PMID: 29868546 PMCID: PMC5962700 DOI: 10.3389/fpubh.2018.00139] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/14/2017] [Accepted: 04/23/2018] [Indexed: 12/02/2022] Open
Abstract
Introduction: Early infant diagnosis (EID) of Human Immunodeficiency Virus (HIV) provides an opportunity for follow up of HIV exposed children for early detection of infection and timely access to antiretroviral treatment. We assessed predictors for accessing HIV diagnostic services among under-five children exposed to HIV infection in Muheza district, Tanzania. Methods: A cross sectional facility-based study among mother/guardian-child pairs of HIV exposed children was conducted from June 2015 to June 2016. Using a structured questionnaire, we collected information on HIV status, socio-demographic characteristics and other relevant data. Multiple regression analyses were used to investigate associations of potential predictors of accessing EID services. Results: A total of 576 children with their respective mothers/guardians were recruited. Of the 576 mothers/guardians, 549 (95.3%) were the biological mothers with a median age of 34 years (inter-quartile range: 30–38 years). The median age of the 576 children was 15 months (inter- quartile range: 8.5–38.0 months). A total of 251 (43.6%) children were born to mothers with unknown HIV status at conception. Only 329 (57.1%) children accessed EID between 4 and 6 weeks of age. Children born to mothers with unknown HIV status at conception (AOR = 0.6, 95% CI 0.4–0.8) and those with ages 13–59 months (AOR = 0.4, 95% CI 0.2–0.6) were the significant predictors of missed opportunity to access EID. Children living with the head of household with at least a high education level had higher chances of accessing EID (AOR = 1.8, 95% CI 1.1–3.3). Their chances of accessing EID services was three-fold higher among mothers/guardians with good knowledge of HIV infection prevention of mother to child transmission (AOR = 3.2, 95% CI 2.0–5.2) than those with poor knowledge. Mothers/guardians living in rural areas had poorer knowledge of HIV infection prevention of mother to child transmission (AOR = 0.6, 95% CI 0.4–0.9) than those living in urban areas. Conclusion: Accessibility of EID services among children below 5 years exposed to HIV infection in Muheza is low. These findings stress the need for continued HIV education and outreach services, particularly in rural areas in order to improve maternal and child health.
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Affiliation(s)
- Veneranda M Bwana
- School of Public Health, University of Zambia, Lusaka, Zambia.,Amani Research Centre, National Institute for Medical Research, Muheza, Tanzania
| | | | - Edgar Simulundu
- Department of Disease Control, School of Veterinary Medicine, University of Zambia, Lusaka, Zambia
| | - Leonard E G Mboera
- National Institute for Medical Research, Headquarters, Dar es Salaam, Tanzania
| | - Charles Michelo
- School of Public Health, University of Zambia, Lusaka, Zambia.,Strategic Centre for Health Systems Metrics and Evaluations, School of Public Health, University of Zambia, Lusaka, Zambia
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Desmonde S, Tanser F, Vreeman R, Takassi E, Edmonds A, Lumbiganon P, Pinto J, Malateste K, McGowan C, Kariminia A, Yotebieng M, Dicko F, Yiannoutsos C, Mubiana-Mbewe M, Wools-Kaloustian K, Davies MA, Leroy V. Access to antiretroviral therapy in HIV-infected children aged 0-19 years in the International Epidemiology Databases to Evaluate AIDS (IeDEA) Global Cohort Consortium, 2004-2015: A prospective cohort study. PLoS Med 2018; 15:e1002565. [PMID: 29727458 PMCID: PMC5935422 DOI: 10.1371/journal.pmed.1002565] [Citation(s) in RCA: 31] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/01/2017] [Accepted: 04/04/2018] [Indexed: 11/19/2022] Open
Abstract
INTRODUCTION Access to antiretroviral therapy (ART) is a global priority. However, the attrition across the continuum of care for HIV-infected children between their HIV diagnosis and ART initiation is not well known. We analyzed the time from enrollment into HIV care to ART initiation in HIV-infected children within the International Epidemiology Databases to Evaluate AIDS (IeDEA) Global Cohort Consortium. METHODS AND FINDINGS We included 135,479 HIV-1-infected children, aged 0-19 years and ART-naïve at enrollment, between 1 January 2004 and 31 December 2015, in IeDEA cohorts from Central Africa (3 countries; n = 4,948), East Africa (3 countries; n = 22,827), West Africa (7 countries; n = 7,372), Southern Africa (6 countries; n = 93,799), Asia-Pacific (6 countries; n = 4,045), and Latin America (7 countries; n = 2,488). Follow-up in these cohorts is typically every 3-6 months. We described time to ART initiation and missed opportunities (death or loss to follow-up [LTFU]: last clinical visit >6 months) since baseline (the date of HIV diagnosis or, if unavailable, date of enrollment). Cumulative incidence functions (CIFs) for and determinants of ART initiation were computed, with death and LTFU as competing risks. Among the 135,479 children included, 99,404 (73.4%) initiated ART, 1.9% died, 1.4% were transferred out, and 20.4% were lost to follow-up before ART initiation. The 24-month CIF for ART initiation was 68.2% (95% CI: 67.9%-68.4%); it was lower in sub-Saharan Africa-ranging from 49.8% (95% CI: 48.4%-51.2%) in Central Africa to 72.5% (95% CI: 71.5%-73.5%) in West Africa-compared to Latin America (71.0%, 95% CI: 69.1%-72.7%) and the Asia-Pacific (78.3%, 95% CI: 76.9%-79.6%). Adolescents aged 15-19 years and infants <1 year had the lowest cumulative incidence of ART initiation compared to other ages: 62.2% (95% CI: 61.6%-62.8%) and 66.4% (95% CI: 65.7%-67.0%), respectively. Overall, 49.1% were ART-eligible per local guidelines at baseline, of whom 80.6% initiated ART. The following children had lower cumulative incidence of ART initiation: female children (p < 0.01); those aged <1 year, 2-4 years, 5-9 years, and 15-19 years (versus those aged 10-14 years, p < 0.01); those who became eligible during follow-up (versus eligible at enrollment, p < 0.01); and those receiving care in low-income or lower-middle-income countries (p < 0.01). The main limitations of our study include left truncation and survivor bias, caused by deaths of children prior to enrollment, and use of enrollment date as a proxy for missing data on date of HIV diagnosis, which could have led to underestimation of the time between HIV diagnosis and ART initiation. CONCLUSIONS In this study, 68% of HIV-infected children initiated ART by 24 months. However, there was a substantial risk of LTFU before ART initiation, which may also represent undocumented mortality. In 2015, many obstacles to ART initiation remained, with substantial inequities. More effective and targeted interventions to improve access are needed to reach the target of treating 90% of HIV-infected children with ART.
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Affiliation(s)
| | - Franck Tanser
- Africa Centre for Health and Population Studies, University of KwaZulu-Natal, Somkhele, South Africa
| | - Rachel Vreeman
- School of Medicine, Indiana University, Indianapolis, Indiana, United States of America
| | | | - Andrew Edmonds
- Department of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, United States of America
| | | | - Jorge Pinto
- School of Medicine, Universide Federal de Minas Gerais, Belo Horizonte, Brazil
| | - Karen Malateste
- Inserm U1219, University of Bordeaux, Bordeaux, France
- Bordeaux School of Public Health, University of Bordeaux, Bordeaux, France
| | - Catherine McGowan
- Division of Infectious Diseases, Vanderbilt University Medical Center, Nashville, Tennessee, United States of America
| | - Azar Kariminia
- Kirby Institute, University of New South Wales, Sydney, New South Wales, Australia
| | - Marcel Yotebieng
- Division of Epidemiology, College of Public Health, Ohio State University, Columbus, Ohio, United States of America
| | | | - Constantin Yiannoutsos
- Richard M. Fairbanks School of Public Health, Indiana University, Indianapolis, Indiana, United States of America
| | | | - Kara Wools-Kaloustian
- School of Medicine, Indiana University, Indianapolis, Indiana, United States of America
| | - Mary-Ann Davies
- Centre for Infectious Disease Epidemiology and Research, School of Public Health and Family Medicine, University of Cape Town, Cape Town, South Africa
| | - Valériane Leroy
- Inserm U1027, Toulouse III University, Toulouse, France
- * E-mail:
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Peter T, Zeh C, Katz Z, Elbireer A, Alemayehu B, Vojnov L, Costa A, Doi N, Jani I. Scaling up HIV viral load - lessons from the large-scale implementation of HIV early infant diagnosis and CD4 testing. J Int AIDS Soc 2018; 20 Suppl 7. [PMID: 29130601 PMCID: PMC5978645 DOI: 10.1002/jia2.25008] [Citation(s) in RCA: 35] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/06/2017] [Accepted: 08/21/2017] [Indexed: 01/09/2023] Open
Abstract
INTRODUCTION The scale-up of effective HIV viral load (VL) testing is an urgent public health priority. Implementation of testing is supported by the availability of accurate, nucleic acid based laboratory and point-of-care (POC) VL technologies and strong WHO guidance recommending routine testing to identify treatment failure. However, test implementation faces challenges related to the developing health systems in many low-resource countries. The purpose of this commentary is to review the challenges and solutions from the large-scale implementation of other diagnostic tests, namely nucleic-acid based early infant HIV diagnosis (EID) and CD4 testing, and identify key lessons to inform the scale-up of VL. DISCUSSION Experience with EID and CD4 testing provides many key lessons to inform VL implementation and may enable more effective and rapid scale-up. The primary lessons from earlier implementation efforts are to strengthen linkage to clinical care after testing, and to improve the efficiency of testing. Opportunities to improve linkage include data systems to support the follow-up of patients through the cascade of care and test delivery, rapid sample referral networks, and POC tests. Opportunities to increase testing efficiency include improvements to procurement and supply chain practices, well connected tiered laboratory networks with rational deployment of test capacity across different levels of health services, routine resource mapping and mobilization to ensure adequate resources for testing programs, and improved operational and quality management of testing services. If applied to VL testing programs, these approaches could help improve the impact of VL on ART failure management and patient outcomes, reduce overall costs and help ensure the sustainable access to reduced pricing for test commodities, as well as improve supportive health systems such as efficient, and more rigorous quality assurance. These lessons draw from traditional laboratory practices as well as fields such as logistics, operations management and business. CONCLUSIONS The lessons and innovations from large-scale EID and CD4 programs described here can be adapted to inform more effective scale-up approaches for VL. They demonstrate that an integrated approach to health system strengthening focusing on key levers for test access such as data systems, supply efficiencies and network management. They also highlight the challenges with implementation and the need for more innovative approaches and effective partnerships to achieve equitable and cost-effective test access.
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Affiliation(s)
- Trevor Peter
- Clinton Health Access Initiative, Gaborone, Botswana
| | - Clement Zeh
- United States Centers for Disease Control, Addis Ababa, Ethiopia
| | - Zachary Katz
- Foundation for Innovative New Diagnostics, Geneva, Switzerland
| | - Ali Elbireer
- African Society for Laboratory Medicine, Addid Ababa, Ethiopia
| | | | - Lara Vojnov
- World Health Organization, Geneva, Switzerland
| | | | - Naoko Doi
- Clinton Health Access Initiative, Gaborone, Botswana
| | - Ilesh Jani
- Institut Nacional Da Saude, Maputo, Mozambique
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Dunning L, Kroon M, Hsiao NY, Myer L. Field evaluation of HIV point-of-care testing for early infant diagnosis in Cape Town, South Africa. PLoS One 2017; 12:e0189226. [PMID: 29261707 PMCID: PMC5738050 DOI: 10.1371/journal.pone.0189226] [Citation(s) in RCA: 27] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/06/2017] [Accepted: 11/21/2017] [Indexed: 12/21/2022] Open
Abstract
Background Early infant HIV diagnosis (EID) coverage and uptake remains challenging. Point-of-care (POC) testing may improve access and turn-around-times, but, while several POC technologies are in development there are few data on their implementation in the field. Methods We conducted an implementation study of the Alere q Detect POC system for EID at two public sector health facilities in Cape Town. HIV-exposed neonates undergoing routine EID testing at a large maternity hospital and a primary care clinic received both laboratory-based HIV PCR testing per local protocols and a POC test. We analysed the performance of POC versus laboratory testing, and conducted semi-structured interviews with providers to assess acceptability and implementation issues. Results Overall 478 specimens were taken: 311 tests were performed at the obstetric hospital (median child age, 1 days) and 167 six-week tests in primary care (median child age, 42 days). 9.0% of all tests resulted in an error with no differences by site; most errors resolved with retesting. POC was more sensitive (100%; lower 95% CI, 39.8%) and specific (100%, lower 95% CI, 98%) among older children tested in primary care compared with birth testing in hospital (90.0%, 95% CI, 55.5–99.8% and 100.0%, lower 95% CI, 98.4%, respectively). Negative predictive value was high (>99%) at both sites. In interviews, providers felt the device was simple to use and facilitated decision-making in the management of infants. However, many wanted clarity on the cause of errors on the POC device to help guide repeat testing. Conclusions POC EID testing performs well in field implementation in health care facilities and appears highly acceptable to health care providers.
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Affiliation(s)
- Lorna Dunning
- Division of Epidemiology and Biostatistics, School of Public Health and Family Medicine, University of Cape Town, Cape Town, South Africa
- Centre for Infectious Diseases Epidemiology and Research, School of Public Health and Family Medicine, University of Cape Town, Cape Town, South Africa
- * E-mail:
| | - Max Kroon
- Department of Neonatal Medicine, University of Cape Town, Cape Town, South Africa
| | - Nei-yuan Hsiao
- Division of Medical Virology, University of Cape Town, Cape Town, South Africa
| | - Landon Myer
- Division of Epidemiology and Biostatistics, School of Public Health and Family Medicine, University of Cape Town, Cape Town, South Africa
- Centre for Infectious Diseases Epidemiology and Research, School of Public Health and Family Medicine, University of Cape Town, Cape Town, South Africa
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Assessing Very Early Infant Diagnosis Turnaround Times: Findings from a Birth Testing Pilot in Lesotho. AIDS Res Treat 2017; 2017:2572594. [PMID: 29410914 PMCID: PMC5749171 DOI: 10.1155/2017/2572594] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/04/2017] [Accepted: 11/14/2017] [Indexed: 11/17/2022] Open
Abstract
Very early infant diagnosis (VEID) (testing within two weeks of life), combined with rapid treatment initiation, could reduce early infant mortality. Our study evaluated turnaround time (TAT) to receipt of infants' HIV test results and ART initiation if HIV-infected, with and without birth testing availability. Data from facility records and national databases were collected for 12 facilities offering VEID, as part of an observational prospective cohort study, and 10 noncohort facilities. HIV-exposed infants born in January-June 2016 and any cohort infant diagnosed as HIV-infected at birth or six weeks were included. The median TAT from blood draw to caregiver result receipt was 76.5 days at birth and 63 and 70 days at six weeks at cohort and noncohort facilities, respectively. HIV-exposed infants tested at birth were approximately one month younger when their caregivers received results versus those tested at six weeks. Infants diagnosed at birth initiated ART about two months earlier (median 6.4 weeks old) than those identified at six weeks (median 14.8 weeks). However, the long TAT for testing at both birth and six weeks illustrates the prolonged process for specimen transport and result return that could compromise the effectiveness of adding VEID to existing overburdened EID systems.
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Dunning L, Kroon M, Fourie L, Ciaranello A, Myer L. Impact of Birth HIV-PCR Testing on the Uptake of Follow-up Early Infant Diagnosis Services in Cape Town, South Africa. Pediatr Infect Dis J 2017; 36:1159-1164. [PMID: 28767616 PMCID: PMC5926182 DOI: 10.1097/inf.0000000000001677] [Citation(s) in RCA: 21] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/13/2023]
Abstract
INTRODUCTION Polymerase chain reaction testing at birth ("birth-testing") is suggested by new World Health Organization guidelines for rapid diagnosis of infants infected with HIV in utero. However, there are few data on the implementation of this approach in sub-Saharan Africa, and whether birth testing affects uptake of subsequent routine early infant diagnosis (EID) testing at 6-10 weeks of age is unknown. METHODS We reviewed 575 consecutive infants undergoing targeted high-risk birth testing in Cape Town, South Africa, and matched those testing HIV negative at birth (n = 551) to HIV-exposed infants who did not receive birth testing (n = 551). Maternal and infant clinical and demographic data, including EID testing uptake, were abstracted from routine records. RESULTS Overall, 3.8% of all birth tests conducted were positive while later EID testing positivity rates were 0.5% for those infants testing HIV negative at birth and 0.4% for those without birth testing. Infants who underwent birth testing were less likely to present for later EID compared with those without a birth test (73% vs. 85%; P < 0.001). This difference persisted after adjusting for maternal and infant characteristics (adjusted odds ratio, 0.60; 95% confidence interval: 0.41-0.86) and across demographic and clinical subgroups. Infants undergoing birth testing also presented for later EID at a significantly older age (mean age, 60 vs. 50 days; P < 0.001). CONCLUSIONS While the yield of targeted high-risk birth testing in this setting appears high, neonates testing HIV negative at birth may be less likely to present for subsequent EID testing. For birth testing implementation to contribute to overall EID program goals, structured interventions are required to support follow-up EID services after negative birth test results.
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Affiliation(s)
- Lorna Dunning
- Division of Epidemiology & Biostatistics, School of Public Health and Family Medicine, University of Cape Town, Cape Town, South Africa
| | - Max Kroon
- Department of Neonatal Medicine, University of Cape Town, Cape Town, South Africa
| | - Lezanne Fourie
- Department of Neonatal Medicine, University of Cape Town, Cape Town, South Africa
| | - Andrea Ciaranello
- Division of Infectious Disease, Medical Practice Evaluation Center, Massachusetts General Hospital, Boston, MA, USA
| | - Landon Myer
- Division of Epidemiology & Biostatistics, School of Public Health and Family Medicine, University of Cape Town, Cape Town, South Africa
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Dunning L, Francke JA, Mallampati D, MacLean RL, Penazzato M, Hou T, Myer L, Abrams EJ, Walensky RP, Leroy V, Freedberg KA, Ciaranello A. The value of confirmatory testing in early infant HIV diagnosis programmes in South Africa: A cost-effectiveness analysis. PLoS Med 2017; 14:e1002446. [PMID: 29161262 PMCID: PMC5697827 DOI: 10.1371/journal.pmed.1002446] [Citation(s) in RCA: 29] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/03/2016] [Accepted: 10/18/2017] [Indexed: 11/18/2022] Open
Abstract
BACKGROUND The specificity of nucleic acid amplification tests (NAATs) used for early infant diagnosis (EID) of HIV infection is <100%, leading some HIV-uninfected infants to be incorrectly identified as HIV-infected. The World Health Organization recommends that infants undergo a second NAAT to confirm any positive test result, but implementation is limited. Our objective was to determine the impact and cost-effectiveness of confirmatory HIV testing for EID programmes in South Africa. METHOD AND FINDINGS Using the Cost-effectiveness of Preventing AIDS Complications (CEPAC)-Pediatric model, we simulated EID testing at age 6 weeks for HIV-exposed infants without and with confirmatory testing. We assumed a NAAT cost of US$25, NAAT specificity of 99.6%, NAAT sensitivity of 100% for infants infected in pregnancy or at least 4 weeks prior to testing, and a mother-to-child transmission (MTCT) rate at 12 months of 4.9%; we simulated guideline-concordant rates of testing uptake, result return, and antiretroviral therapy (ART) initiation (100%). After diagnosis, infants were linked to and retained in care for 10 years (false-positive) or lifelong (true-positive). All parameters were varied widely in sensitivity analyses. Outcomes included number of infants with false-positive diagnoses linked to ART per 1,000 ART initiations, life expectancy (LE, in years) and per-person lifetime HIV-related healthcare costs. Both without and with confirmatory testing, LE was 26.2 years for HIV-infected infants and 61.4 years for all HIV-exposed infants; clinical outcomes for truly infected infants did not differ by strategy. Without confirmatory testing, 128/1,000 ART initiations were false-positive diagnoses; with confirmatory testing, 1/1,000 ART initiations were false-positive diagnoses. Because confirmatory testing averted costly HIV care and ART in truly HIV-uninfected infants, it was cost-saving: total cost US$1,790/infant tested, compared to US$1,830/infant tested without confirmatory testing. Confirmatory testing remained cost-saving unless NAAT cost exceeded US$400 or the HIV-uninfected status of infants incorrectly identified as infected was ascertained and ART stopped within 3 months of starting. Limitations include uncertainty in the data used in the model, which we examined with sensitivity and uncertainty analyses. We also excluded clinical harms to HIV-uninfected infants incorrectly treated with ART after false-positive diagnosis (e.g., medication toxicities); including these outcomes would further increase the value of confirmatory testing. CONCLUSIONS Without confirmatory testing, in settings with MTCT rates similar to that of South Africa, more than 10% of infants who initiate ART may reflect false-positive diagnoses. Confirmatory testing prevents inappropriate HIV diagnosis, is cost-saving, and should be adopted in all EID programmes.
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Affiliation(s)
- Lorna Dunning
- Division of Epidemiology and Biostatistics, School of Public Health & Family Medicine, University of Cape Town, Cape Town, South Africa
- Medical Practice Evaluation Centre, Department of Medicine, Massachusetts General Hospital, Boston, Massachusetts, United States of America
| | - Jordan A. Francke
- Medical Practice Evaluation Centre, Department of Medicine, Massachusetts General Hospital, Boston, Massachusetts, United States of America
| | - Divya Mallampati
- Department of Obstetrics and Gynecology, Northwestern University, Chicago, Illinois, United States of America
| | - Rachel L. MacLean
- Medical Practice Evaluation Centre, Department of Medicine, Massachusetts General Hospital, Boston, Massachusetts, United States of America
| | - Martina Penazzato
- Department of HIV/AIDS, World Health Organization, Geneva, Switzerland
| | - Taige Hou
- Medical Practice Evaluation Centre, Department of Medicine, Massachusetts General Hospital, Boston, Massachusetts, United States of America
| | - Landon Myer
- Division of Epidemiology and Biostatistics, School of Public Health & Family Medicine, University of Cape Town, Cape Town, South Africa
- Centre for Infectious Diseases Epidemiology & Research, School of Public Health & Family Medicine, University of Cape Town, Cape Town, South Africa
| | - Elaine J. Abrams
- ICAP at Columbia University, Mailman School of Public Health, Columbia University, New York, New York, United States of America
- College of Physicians & Surgeons, Columbia University, New York, New York, United States of America
| | - Rochelle P. Walensky
- Medical Practice Evaluation Centre, Department of Medicine, Massachusetts General Hospital, Boston, Massachusetts, United States of America
- Division of Infectious Diseases, Department of Medicine, Massachusetts General Hospital, Boston, Massachusetts, United States of America
- Division of Infectious Diseases, Brigham and Women’s Hospital, Boston, Massachusetts, United States of America
- Center for AIDS Research, Harvard University, Boston, Massachusetts, United States of America
| | | | - Kenneth A. Freedberg
- Medical Practice Evaluation Centre, Department of Medicine, Massachusetts General Hospital, Boston, Massachusetts, United States of America
- Division of Infectious Diseases, Department of Medicine, Massachusetts General Hospital, Boston, Massachusetts, United States of America
- Center for AIDS Research, Harvard University, Boston, Massachusetts, United States of America
- Department of Health Policy and Management, Harvard T.H. Chan School of Public Health, Boston, Massachusetts, United States of America
| | - Andrea Ciaranello
- Medical Practice Evaluation Centre, Department of Medicine, Massachusetts General Hospital, Boston, Massachusetts, United States of America
- Division of Infectious Diseases, Department of Medicine, Massachusetts General Hospital, Boston, Massachusetts, United States of America
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Technau KG, Kuhn L, Coovadia A, Murnane PM, Sherman G. Xpert HIV-1 point-of-care test for neonatal diagnosis of HIV in the birth testing programme of a maternity hospital: a field evaluation study. Lancet HIV 2017; 4:e442-e448. [PMID: 28711526 PMCID: PMC5623143 DOI: 10.1016/s2352-3018(17)30097-8] [Citation(s) in RCA: 43] [Impact Index Per Article: 5.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/30/2016] [Revised: 05/12/2017] [Accepted: 05/12/2017] [Indexed: 01/22/2023]
Abstract
BACKGROUND Point-of-care testing (POCT) among HIV-exposed infants might improve linkage to care relative to laboratory-based testing (LABT). We evaluated HIV-1 POCT at birth in the context of universal LABT in a maternity hospital and describe our implementation experience. METHODS We did a field evaluation study between Oct 1, 2014, and April 30, 2016, at the urban Rahima Moosa Mother and Child Hospital (RMMCH), Johannesburg, South Africa. We aimed to sample consecutive neonates at birth with POCT (Cepheid Xpert HIV-1 Qualitative test) and compared results with those of LABT (Roche COBAS TaqMan HIV-1 Qualitative test) with respect to performance in terms of sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and Cohen's κ coefficient, result return, antiretroviral treatment (ART) initiation, and coverage. FINDINGS 18 268 women delivered livebirths at RMMCH and 4267 (23%) were HIV-positive with 4336 HIV-exposed neonates delivered. Mothers of 4141 (96%) HIV-exposed neonates were offered infant birth testing. Mothers of 4112 (99%) neonates consented. In 78 neonates with consent (2%), a test was not done due to early neonatal death (n=13), mother departing before venesection, or staff unavailability. Among 3970 infants who had LABT, 57 (1%) tested positive, 3906 (99%) tested negative, two (<1%) were indeterminate, and five (<1%) had an error result. 2238 (56%) of these infants had concurrent POCT. POCT detected all 30 HIV-infected neonates (sensitivity 100%; 95% CI 88·4-100) with two additional false-positive results (specificity 99·9%; 99·7-100). All positive and 96·2% of negative POCT results were returned compared with 88·9% of positive and 52·8% of negative LABT results. Although every POCT required 90 min of instrument time, 2·6 h (IQR 2·3-3·1) elapsed between phlebotomy and result return. In days, median time of result return for POCT was 1 day, significantly earlier than 10 days for LABT (p<0·0001). ART was initiated in 30 neonates (100%) with positive POCT compared with 24 (88·9%, p=0·10) of 27 infants who had LABT only, with initiation occurring a median of 5 days earlier in the POCT group (p<0·0001). POCT implementation required additional staff and weekend cover. INTERPRETATION Compared with LABT, POCT was associated with good performance, improved rates of result return, and reduced time to ART initiation. Resources needed to integrate POCT into a routine birth testing programme require further evaluation. FUNDING National Institutes of Health.
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Affiliation(s)
- Karl-Günter Technau
- Empilweni Services and Research Unit, Department of Paediatrics & Child Health, Rahima Moosa Mother and Child Hospital, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa.
| | - Louise Kuhn
- Gertrude H Sergievsky Center, College of Physicians and Surgeons, and Department of Epidemiology, Mailman School of Public Health, Columbia University, New York, NY, USA
| | - Ashraf Coovadia
- Empilweni Services and Research Unit, Department of Paediatrics & Child Health, Rahima Moosa Mother and Child Hospital, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa
| | - Pamela M Murnane
- Empilweni Services and Research Unit, Department of Paediatrics & Child Health, Rahima Moosa Mother and Child Hospital, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa; Gertrude H Sergievsky Center, College of Physicians and Surgeons, and Department of Epidemiology, Mailman School of Public Health, Columbia University, New York, NY, USA
| | - Gayle Sherman
- Centre for HIV and STI, National Institute for Communicable Diseases, Johannesburg, South Africa
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Virological response and resistances over 12 months among HIV-infected children less than two years receiving first-line lopinavir/ritonavir-based antiretroviral therapy in Cote d'Ivoire and Burkina Faso: the MONOD ANRS 12206 cohort. J Int AIDS Soc 2017; 20:21362. [PMID: 28453240 PMCID: PMC5515025 DOI: 10.7448/ias.20.01.21362] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/16/2023] Open
Abstract
Introduction: Lopinavir/ritonavir-based antiretroviral therapy (ART) is recommended for all HIV-infected children less than three years. However, little is known about its field implementation and effectiveness in West Africa. We assessed the 12-month response to lopinavir/ritonavir-based antiretroviral therapy in a cohort of West African children treated before the age of two years. Methods: HIV-1-infected, ART-naive except for a prevention of mother-to-child transmission (PMTCT), tuberculosis-free, and less than two years of age children with parent’s consent were enrolled in a 12-month prospective therapeutic cohort with lopinavir/ritonavir ART and cotrimoxazole prophylaxis in Ouagadougou and Abidjan. Virological suppression (VS) at 12 months (viral load [VL] <500 copies/mL) and its correlates were assessed. Results: Between May 2011 and January 2013, 156 children initiated ART at a median age of 13.9 months (interquartile range: 7.8–18.4); 63% were from Abidjan; 53% were girls; 37% were not exposed to any PMTCT intervention or maternal ART; mother was the main caregiver in 81%; 61% were classified World Health Organization Stage 3 to 4. After 12 months on ART, 11 children had died (7%), 5 were lost-to-follow-up/withdrew (3%), and VS was achieved in 109: 70% of children enrolled and 78% of those followed-up. When adjusting for country and gender, the access to tap water at home versus none (adjusted odds ratio (aOR): 2.75, 95% confidence interval (CI): 1.09–6.94), the mother as the main caregiver versus the father (aOR: 2.82, 95% CI: 1.03–7.71), and the increase of CD4 percentage greater than 10% between inclusion and 6 months versus <10% (aOR: 2.55, 95% CI: 1.05–6.18) were significantly associated with a higher rate of VS. At 12 months, 28 out of 29 children with VL ≥1000 copies/mL had a resistance genotype test: 21 (75%) had ≥1 antiretroviral (ARV) resistance (61% to lamivudine, 29% to efavirenz, and 4% to zidovudine and lopinavir/ritonavir), of which 11 (52%) existed before ART initiation. Conclusions: Twelve-month VS rate on lopinavir/ritonavir-based ART was high, comparable to those in Africa or high-income countries. The father as the main child caregiver and lack of access to tap water are risk factors for viral failure and justify a special caution to improve adherence in these easy-to-identify situations before ART initiation. Public health challenges remain to optimize outcomes in children with earlier ART initiation in West Africa.
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Canals F, Masiá M, Gutiérrez F. Developments in early diagnosis and therapy of HIV infection in newborns. Expert Opin Pharmacother 2017; 19:13-25. [PMID: 28764578 DOI: 10.1080/14656566.2017.1363180] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/19/2022]
Abstract
INTRODUCTION Infants who acquire HIV have an exceptionally high risk of morbidity and mortality if they do not receive antiretroviral therapy (ART). AREAS COVERED This review aims to summarize the currently available evidence on ART in HIV-infected neonates. Data were obtained from literature searches from PubMed, abstracts from International Conferences (2000-2017), and authors' files EXPERT OPINION Current evidence favors early diagnosis and prompt ART of HIV infection in newborns. The precise timing of initiation of ART remains undetermined. Very early (close to birth) ART appears to limit the size of the viral reservoir and may restrict replication-competent virus, but the clinical benefit remains unproven. Among the current options for initial therapy, in full term neonates from 2 weeks of life onwards, a lopinavir/ritonavir-based three-drug regimen is preferred. In term infants, younger than 2 weeks a nevirapine-based regimen is recommended, although there are no clinical trial data supporting that initiating treatment before 2 weeks improves outcome compared to starting afterwards. Existing safety information is insufficient to recommend ART in preterm infants, with pharmacokinetic data available for zidovudine only. If ART is considered in this setting, an individual case assessment of the risk/benefit ratio of treatment should be made.
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Affiliation(s)
- Francisco Canals
- a Department of Infectious Diseases, Hospital General de Elche , Universidad Miguel Hernández , Alicante , Spain.,b Department of Pediatrics , Hospital General de Elche , Alicante , Spain
| | - Mar Masiá
- a Department of Infectious Diseases, Hospital General de Elche , Universidad Miguel Hernández , Alicante , Spain
| | - Félix Gutiérrez
- a Department of Infectious Diseases, Hospital General de Elche , Universidad Miguel Hernández , Alicante , Spain
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