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Hage K, Boyd A, van Santen DK, Brinkman K, Arends J, Lauw F, Rijnders B, van Eeden A, van der Valk M, Newsum A, Matser A, Schinkel J, Prins M. Hepatitis C Treatment and Behavioral Risk Among Men Who Have Sex With Men With HIV: Comparing Interferon and Direct-Acting Antiviral Eras. J Acquir Immune Defic Syndr 2025; 98:90-98. [PMID: 39443822 DOI: 10.1097/qai.0000000000003550] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/13/2024] [Accepted: 10/08/2024] [Indexed: 10/25/2024]
Abstract
BACKGROUND Little is known about the effect of hepatitis C virus (HCV) treatment on sexual risk behavior among men who have sex with men (MSM) with HIV by treatment type (interferon [IFN]-based vs direct-acting antiviral [DAA]-based). SETTING MSM with HIV and recently acquired HCV infection enrolled in the MSM Observational Study of Acute Infection with hepatitis C (MOSAIC) cohort. METHODS Using data from 2009 to 2018, we evaluated risk behavior through a validated HCV risk score (where ≥2 indicated high risk) and its individual risk behaviors. Levels of risk behavior before, during, and after treatment were modeled for each treatment episode using linear and logistic regression with Generalized Estimating Equations adjusting for DAA availability and number of reinfections. RESULTS One hundred forty MSM with a median age of 45 years (interquartile range = 40-49) yielded 180 treatment episodes (n = 131 IFN-based, n = 49 DAA-based). Adjusted mean risk score before, during, and after treatment was 2.4 (95% confidence interval [CI] = 2.1 to 2.6), 0.9 (95% CI = 0.8 to 1.0), and 1.7 (95% CI = 1.5 to 1.8), respectively. Before treatment, no differences in mean HCV risk score or proportion of specific behaviors were found between the regimen groups. During treatment, MSM treated with DAAs had a higher average risk score and proportion of receptive condomless anal sex, sharing toys and unprotected fisting than those treated with IFN. After treatment, the proportion sharing straws were significantly higher in MSM treated with DAAs than in MSM treated with IFN. CONCLUSIONS MSM treated with DAAs, compared with MSM treated with IFN, had higher levels of HCV-related risk behavior during treatment. The higher risk of HCV reinfection in the DAA-era underscores the need for ongoing HCV testing and behavioral interventions against HCV.
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Affiliation(s)
- Kris Hage
- Department of Infectious Diseases, Research and Prevention, Public Health Service of Amsterdam, Amsterdam, the Netherlands
- Amsterdam UMC, University of Amsterdam, Infectious Diseases, Amsterdam, the Netherlands
- Amsterdam Institute for Infection and Immunity, Infectious Diseases, Amsterdam, the Netherlands
| | - Anders Boyd
- Department of Infectious Diseases, Research and Prevention, Public Health Service of Amsterdam, Amsterdam, the Netherlands
- Amsterdam UMC, University of Amsterdam, Infectious Diseases, Amsterdam, the Netherlands
- Amsterdam Institute for Infection and Immunity, Infectious Diseases, Amsterdam, the Netherlands
- Stichting hiv monitoring, Amsterdam, the Netherlands
| | - Daniela K van Santen
- Department of Infectious Diseases, Research and Prevention, Public Health Service of Amsterdam, Amsterdam, the Netherlands
- Disease Elimination Program, Burnet Institute, Melbourne, Australia
| | - Kees Brinkman
- Department of Internal Medicine, Onze Lieve Vrouwe Gasthuis (OLVG), Amsterdam, the Netherlands
| | - Joop Arends
- Department of Health, Medicine and Life Sciences, Maastricht University, Maastricht, the Netherlands
| | - Fanny Lauw
- Department of Internal Medicine, Medical Centre Jan van Goyen, Amsterdam, the Netherlands
| | - Bart Rijnders
- Department of Internal Medicine and Infectious Diseases, Erasmus University Medical Center, Rotterdam, the Netherlands
| | - Arne van Eeden
- Department of Internal Medicine, DC Klinieken Lairesse, Amsterdam, the Netherlands; and
| | - Marc van der Valk
- Amsterdam Institute for Infection and Immunity, Infectious Diseases, Amsterdam, the Netherlands
- Stichting hiv monitoring, Amsterdam, the Netherlands
| | - Astrid Newsum
- Department of Infectious Diseases, Research and Prevention, Public Health Service of Amsterdam, Amsterdam, the Netherlands
- Amsterdam Institute for Infection and Immunity, Infectious Diseases, Amsterdam, the Netherlands
| | - Amy Matser
- Department of Infectious Diseases, Research and Prevention, Public Health Service of Amsterdam, Amsterdam, the Netherlands
- Amsterdam Institute for Infection and Immunity, Infectious Diseases, Amsterdam, the Netherlands
| | - Janke Schinkel
- Department of Medical Microbiology & Infection Prevention, Section of Clinical Virology, Amsterdam Infection & Immunity Institute, Amsterdam UMC, University of Amsterdam, Amsterdam, the Netherlands
| | - Maria Prins
- Department of Infectious Diseases, Research and Prevention, Public Health Service of Amsterdam, Amsterdam, the Netherlands
- Amsterdam UMC, University of Amsterdam, Infectious Diseases, Amsterdam, the Netherlands
- Amsterdam Institute for Infection and Immunity, Infectious Diseases, Amsterdam, the Netherlands
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Lee S, Lee JE, Lee SO, Lee SH. Treatment Outcomes of HCV Infection in People Living with HIV: A Case Series from a Single Center in Korea. Infect Chemother 2024; 56:386-394. [PMID: 39370124 PMCID: PMC11458507 DOI: 10.3947/ic.2024.0074] [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: 07/04/2024] [Accepted: 08/26/2024] [Indexed: 10/08/2024] Open
Abstract
BACKGROUND Limited information is available on the clinical course and treatment outcomes of human immunodeficiency virus (HIV) and hepatitis C virus (HCV) coinfection in Korea. MATERIALS AND METHODS A retrospective case series was conducted of patients with HIV-HCV coinfection who received interferon (IFN)-based or direct-acting antiviral (DAA) treatment for HCV at a tertiary care hospital between 2000 and 2023. Early virological response (EVR) was defined as a 2-log reduction in HCV RNA levels or undetectable HCV RNA levels at treatment week 12. A sustained virologic response (SVR) was defined as undetectable HCV RNA at 12 weeks after treatment completion. RESULTS Of the 33 patients with HIV-HCV coinfection, 19 received anti-HCV treatment, of whom 12 received IFN-based treatment and 10 received DAA treatment. The median age at the time of anti-HCV treatment was 49 years (interquartile range, 42-57 years) and 15 patients (79%) were male. Of the 12 patients who received IFN-based anti-HCV treatment, 10 showed EVR and 8 achieved SVR. However, 2 patients who achieved SVR experienced recurrence of HCV infection during follow-up; therefore, the overall success rate of IFN-based treatment was 50% (6/12). All 10 patients (including 3 in whom IFN-based treatment failed) who received DAA treatment (5 with previous anti-HCV treatment and 5 treatment-naïve), achieved SVR and did not experience recurrence of HCV infection during follow-up; therefore, the overall success rate of DAA treatment was 100%. CONCLUSION In Korean patients with HIV-HCV coinfection, treatment outcomes were better with DAA treatment than with IFN-based treatment.
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Affiliation(s)
- Shinwon Lee
- Department of Internal Medicine, Pusan National University School of Medicine and Medical Research Institute, Pusan National University Hospital, Busan, Korea
| | - Jeong Eun Lee
- Department of Internal Medicine, Pusan National University School of Medicine and Medical Research Institute, Pusan National University Hospital, Busan, Korea
| | - Soon Ok Lee
- Department of Internal Medicine, Pusan National University School of Medicine and Medical Research Institute, Pusan National University Hospital, Busan, Korea
| | - Sun Hee Lee
- Department of Internal Medicine, Pusan National University School of Medicine and Medical Research Institute, Pusan National University Hospital, Busan, Korea.
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Crespi A, Van Uum R, Lathouris H, Masterman C, Muncaster K, Gaete K, Capraru C, Shah H, Feld JJ, Biondi MJ. Increasing linkage to hepatitis C care following trauma-informed rehabilitation: An education and quality improvement project among women. Drug Alcohol Rev 2024; 43:1093-1103. [PMID: 37439376 DOI: 10.1111/dar.13713] [Citation(s) in RCA: 2] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/14/2022] [Revised: 05/19/2023] [Accepted: 06/16/2023] [Indexed: 07/14/2023]
Abstract
INTRODUCTION The on-going substance use crisis has led to unprecedented rates of hepatitis C virus (HCV) in Canada, with increasing positivity among women who use drugs (WWUD). Despite efforts to reduce barriers to HCV testing and treatment, follow-up remains a major issue. METHODS In this quality improvement project (QIP), we partnered with a short-stay trauma-informed residential drug treatment facility specifically for WWUD, to provide an engaging peer-led HCV education session, followed by low-barrier nurse and peer-led testing and treatment. We sought to evaluate these interventions, as well as determine what factors could improve engagement after women leave. RESULTS The session was attended by 217 participants, 130 completed the survey and 153 opted into testing. Survey results indicated that participants were highly motivated to access general care as well as HCV testing and treatment. The most frequently reported barriers to testing and treatment were a previous negative test and being asymptomatic, respectively. Follow-up facilitators included a non-judgmental provider (88%), monetary incentives (67%), follow-up phone calls (77%), e-mails (66%) and text messages (58%). Of those who were RNA positive, 5 of 13 initiated treatment on-site. By using the results of the QIP in real-time, 6 of 13 were started after leaving the centre (one pending and one lost to follow-up). DISCUSSION AND CONCLUSIONS The implementation of co-localised peer-led testing and treatment for HCV, along with persistent follow-up efforts, led to increases in linkage to care and treatment. Co-localisation of testing and care with substance-use services, especially if residential, is a viable, low-barrier strategy for increasing linkage to care among WWUD.
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Affiliation(s)
- Agustina Crespi
- Toronto Centre for Liver Disease/VIRCAN, University Health Network, Toronto, Canada
| | | | | | - Chelsea Masterman
- Arthur Labatt Family School of Nursing, Western University, London, Canada
| | - Kody Muncaster
- Department of Gender, Sexuality, & Women's Studies, Western University, London, Canada
| | - Kayla Gaete
- School of Nursing, York University, Toronto, Canada
| | - Camelia Capraru
- Toronto Centre for Liver Disease/VIRCAN, University Health Network, Toronto, Canada
| | - Hemant Shah
- Toronto Centre for Liver Disease/VIRCAN, University Health Network, Toronto, Canada
| | - Jordan J Feld
- Toronto Centre for Liver Disease/VIRCAN, University Health Network, Toronto, Canada
| | - Mia J Biondi
- Toronto Centre for Liver Disease/VIRCAN, University Health Network, Toronto, Canada
- School of Nursing, York University, Toronto, Canada
- Omega Specialty Nurses, Toronto, Canada
- Arthur Labatt Family School of Nursing, Western University, London, Canada
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Dobrowolska K, Brzdęk M, Rzymski P, Flisiak R, Pawłowska M, Janczura J, Brzdęk K, Zarębska-Michaluk D. Revolutionizing hepatitis C treatment: next-gen direct-acting antivirals. Expert Opin Pharmacother 2024; 25:833-852. [PMID: 38768013 DOI: 10.1080/14656566.2024.2358139] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/11/2024] [Accepted: 05/17/2024] [Indexed: 05/22/2024]
Abstract
INTRODUCTION With the introduction of highly effective and safe therapies with next-generation direct-acting antivirals (DAAs), that act without interferon, hepatitis C virus (HCV) infection remains the only treatable chronic infectious disease. AREAS COVERED The review aims to provide an overview of the therapy revolution with a description of specific DAAs, their mechanisms of action, a summary of the safety and efficacy of specific regimens, and a discussion of populations requiring special therapeutic approaches. EXPERT OPINION DAAs are highly effective, safe, and easy to use. However, challenges such as access to health services and loss of patients from the cascade of care, especially in groups disproportionately affected by HCV infection, such as substance abusers, make it difficult to achieve the WHO's goal of HCV elimination. The proposed strategy to combat these difficulties involves a one-step approach to diagnosing and treating the infection, the availability of long-lasting forms of medication, and the development of an effective vaccine. The aforementioned opportunities are all the more important as the world is facing an opioid epidemic that is translating into an increase in HCV prevalence. This phenomenon is of greatest concern in women of childbearing age and in those already pregnant due to treatment limitations.
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Affiliation(s)
| | - Michał Brzdęk
- Collegium Medicum, Jan Kochanowski University, Kielce, Poland
| | - Piotr Rzymski
- Department of Environmental Medicine, Poznan University of Medical Sciences, Poznan, Poland
| | - Robert Flisiak
- Department of Infectious Diseases and Hepatology, Medical University of Białystok, Białystok, Poland
| | - Małgorzata Pawłowska
- Department of Infectious Diseases and Hepatology, Faculty of Medicine, Collegium Medicum Bydgoszcz, Nicolaus Copernicus University, Toruń, Poland
| | - Jakub Janczura
- Collegium Medicum, Jan Kochanowski University, Kielce, Poland
| | - Kinga Brzdęk
- Collegium Medicum, Jan Kochanowski University, Kielce, Poland
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Brzdęk M, Zarębska-Michaluk D, Invernizzi F, Cilla M, Dobrowolska K, Flisiak R. Decade of optimizing therapy with direct-acting antiviral drugs and the changing profile of patients with chronic hepatitis C. World J Gastroenterol 2023; 29:949-966. [PMID: 36844142 PMCID: PMC9950869 DOI: 10.3748/wjg.v29.i6.949] [Citation(s) in RCA: 13] [Impact Index Per Article: 6.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/12/2022] [Revised: 11/22/2022] [Accepted: 01/09/2023] [Indexed: 02/10/2023] Open
Abstract
Chronic infection with the hepatitis C virus (HCV) remains a major health problem affecting approximately 58 million people worldwide. In the era of interferon (IFN)-based regimens, patients particularly infected with genotypes 1 and 4 achieved a low response rate. The implementation of direct-acting antivirals changed the landscape of HCV treatment. The increase in effectiveness provided us with the hope of eliminating HCV as a significant public threat by 2030. In the following years, there was an observed improvement in the treatment of HCV with genotype-specific regimens and highly effective pangenotypic options that are the most recent stage of the revolution. The optimization of therapy was accompanied by changes in the patient profile from the beginning of the IFN-free era over time. Patients treated with antiviral therapies were younger in successive periods, less burdened with comorbidities and comedications, more frequently treatment-naïve and had less advanced liver disease. Before the IFN-free era, specific subpopulations such as patients with HCV/HIV coinfection, those with a history of previous treatment, patients with renal impairment or with cirrhosis had lower chances for a virologic response. Currently, these populations should no longer be considered difficult to treat. Despite the high effectiveness of HCV therapy, there is a small percentage of patients with treatment failure. However, they can be effectively retreated with pangenotypic rescue regimens.
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Affiliation(s)
- Michał Brzdęk
- Collegium Medicum, Jan Kochanowski University, Kielce 25-516, Poland
| | | | - Federica Invernizzi
- Center for Liver Disease, Division of Internal Medicine and Hepatology, IRCCS Ospedale San Raffaele, Milan 20-132, Italy
| | - Marta Cilla
- Center for Liver Disease, Division of Internal Medicine and Hepatology, IRCCS Ospedale San Raffaele, Milan 20-132, Italy
| | | | - Robert Flisiak
- Department of Infectious Diseases and Hepatology, Medical University of Białystok, Białystok 15-540, Poland
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Nyein PP, Tillakeratne S, Phyu S, Yee MM, Lwin MM, Htike KL, Aung MT, Grebely J, Applegate T, Hanson J, Matthews G, Lin KS. Evaluation of Simplified HCV Diagnostics in HIV/HCV Co-Infected Patients in Myanmar. Viruses 2023; 15:v15020521. [PMID: 36851736 PMCID: PMC9967037 DOI: 10.3390/v15020521] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/03/2022] [Revised: 02/06/2023] [Accepted: 02/08/2023] [Indexed: 02/16/2023] Open
Abstract
To evaluate a decentralised testing model and simplified treatment protocol of hepatitis C virus (HCV) infection to facilitate treatment scale-up in Myanmar, this prospective, observational study recruited HIV-HCV co-infected outpatients receiving sofosbuvir/daclatasvir in Yangon, Myanmar. The study examined the outcomes and factors associated with a sustained virological response (SVR). A decentralised "hub-and-spoke" testing model was evaluated where fingerstick capillary specimens were transported by taxi and processed centrally. The performance of the Xpert HCV VL Fingerstick Assay in detecting HCV RNA was compared to the local standard of care ( plasma HCV RNA collected by venepuncture). Between January 2019 and February 2020, 162 HCV RNA-positive individuals were identified; 154/162 (95%) initiated treatment, and 128/154 (84%) returned for their SVR12 visit. A SVR was achieved in 119/154 (77%) participants in the intent-to-treat population and 119/128 (93%) participants in the modified-intent-to-treat population. Individuals receiving an antiretroviral therapy were more likely to achieve a SVR (with an odds ratio (OR) of 7.16, 95% CI 1.03-49.50), while those with cirrhosis were less likely (OR: 0.26, 95% CI 0.07-0.88). The sensitivity of the Xpert HCV VL Fingerstick Assay was 99.4% (95% CI 96.7-100.0), and the specificity was 99.2% (95% CI 95.9-99.9). A simplified treatment protocol using a hub-and-spoke testing model of fingerstick capillary specimens can achieve an SVR rate in LMIC comparable to well-resourced high-income settings.
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Affiliation(s)
| | - Shane Tillakeratne
- The Kirby Institute, University of New South Wales, Sydney, NSW 2052, Australia
- Correspondence:
| | - Sabai Phyu
- Department of Tropical and Infectious Diseases, Specialist Hospital Waibargi, Yangon W5C4+6J7, Myanmar
| | | | - Mya Mya Lwin
- Department of Microbiology, University of Medicine 2, Yangon 644-704, Myanmar
| | - Kyaw Linn Htike
- Myanmar-Australia Research Collaboration for Health Laboratory, Yangon W5C4+6J7, Myanmar
| | - May Thu Aung
- Myanmar-Australia Research Collaboration for Health Laboratory, Yangon W5C4+6J7, Myanmar
| | - Jason Grebely
- The Kirby Institute, University of New South Wales, Sydney, NSW 2052, Australia
| | - Tanya Applegate
- The Kirby Institute, University of New South Wales, Sydney, NSW 2052, Australia
| | - Josh Hanson
- The Kirby Institute, University of New South Wales, Sydney, NSW 2052, Australia
- Cairns and Hinterland Hospital and Health Service, Cairns North, QLD 4870, Australia
| | - Gail Matthews
- The Kirby Institute, University of New South Wales, Sydney, NSW 2052, Australia
| | - Kyaw Swar Lin
- Specialist Hospital Mingaladon, Yangon X42H+J4, Myanmar
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Khemnark S, Manosuthi W. Real-world treatment outcomes of sofosbuvir-based regimens for treatment of chronic hepatitis C with and without human immunodeficiency virus co-infection. JGH Open 2023; 7:157-162. [PMID: 36852142 PMCID: PMC9958333 DOI: 10.1002/jgh3.12869] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/23/2022] [Revised: 01/09/2023] [Accepted: 01/12/2023] [Indexed: 01/28/2023]
Abstract
Background and Aim The efficacy of sofosbuvir (SOF)-based regimens in the treatment of chronic hepatitis C (HCV) patients with and without human immunodeficiency virus (HIV) co-infected patients in real-world setting is limited. Methods This was a retrospective cohort study, conducted between 1 January 2017 and 31 December 2021 at Bamrasnaradura Infectious Disease Institute, Thailand. All HCV patients received 12 weeks of SOF-based regimens and had follow-up for at least 12 weeks after therapy discontinuation. The primary outcome was sustained virological response (SVR) at 12 weeks after the end of treatment. Treatment outcomes were compared between HCV patients with and without HIV co-infection. Results A total of 163 patients were included in the study, 130 (79.8%) were HCV/HIV co-infected, and 33 (20.2%) were HCV mono-infected. Of all, 106 (64%) patients received SOF and ledipasvir. Genotype 1 (GT1) was predominant at 66.4%, followed by GT3 at 22.2%, and GT6 at 11.4%. Overall SVR was 96.9%. SVR in HCV mono-infected was 96.9% and SVR in HIV-HCV co-infected patients was 96.9%. The factor associated with SVR was HCV genotype (P = 0.001). Patients with HCV GT6 had lower SVR rates compared with GT1 and GT3 patients (83.3%, 100%, and 97.1% [P = 0.000] respectively). There was no association between SVR and other factors such as gender, age, BMI, underlying cirrhosis, baseline HCV viral load, or prior treatment history (all P > 0.05). All patients completed 12-week SOF-based treatment. Conclusion In real-world setting, HCV treatment with SOF-based regimens between patients with and without HIV co-infection showed high rates of SVR. SOF-based regimens were highly efficacious and tolerated.
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Affiliation(s)
- Suparat Khemnark
- Department of MedicineBamrasnaradura Infectious Disease Institute, Ministry of Public HealthNonthaburiThailand
| | - Weerawat Manosuthi
- Department of MedicineBamrasnaradura Infectious Disease Institute, Ministry of Public HealthNonthaburiThailand
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Zarębska-Michaluk D, Brzdęk M, Jaroszewicz J, Tudrujek-Zdunek M, Lorenc B, Klapaczyński J, Mazur W, Kazek A, Sitko M, Berak H, Janocha-Litwin J, Dybowska D, Supronowicz Ł, Krygier R, Citko J, Piekarska A, Flisiak R. Best therapy for the easiest to treat hepatitis C virus genotype 1b-infected patients. World J Gastroenterol 2022; 28:6380-6396. [PMID: 36533109 PMCID: PMC9753050 DOI: 10.3748/wjg.v28.i45.6380] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/26/2022] [Revised: 10/01/2022] [Accepted: 11/19/2022] [Indexed: 12/02/2022] Open
Abstract
BACKGROUND The revolution in treatment of patients with chronic hepatitis C virus (HCV) infection dates back to the introduction of direct-acting antivirals (DAAs). The increase in efficacy was most pronounced in patients infected with genotype (GT) 1b, as this was the most poorly responsive population to treatment during the interferon era.
AIM To identify the most effective interferon-free therapy for GT1b-infected patients and to determine positive and negative predictors of virological response.
METHODS This real-world retrospective analysis included patients chronically infected with GT1b HCV whose data were obtained from the multicenter observational EpiTer-2 database. Treatment effectiveness was evaluated for each therapeutic regimen as the percentage of sustained virological responses (SVR). Assessment of the safety was based on the evaluation of the course of therapy, the occurrence of adverse events including serious ones, deaths during treatment and in the post 12-wk follow-up period.
RESULTS The studied population consisted of 11385 patients with a mean age of 53 ± 14.8 years and a female predominance (53.4%). The majority of them were treatment-naïve (74.6%) and patients with cirrhosis accounted for 24.3%. Of the DAA regimens used, 76.9% were GT-specific with ombitasvir/paritaprevir/ritonavir + dasabuvir ± ribavirin being the most used option (32.4%). A total of 10903 patients responded to treatment resulting in a 98.1% in the per-protocol analysis after excluding 273 patients without SVR data. The effectiveness of all regimens exceeded 90% and the highest SVR of 98.9% was achieved in patients treated with a combination of glecaprevir/pibrentasvir. Logistic regression analyses showed that the virologic response was independently associated with female sex [odds ratio (OR) = 1.67], absence of decompensated cirrhosis at baseline (OR = 2.42) and higher baseline platelets (OR = 1.004 per 1000/μL increase), while the presence of human immunodeficiency virus (HIV) coinfection significantly decreased the odds of response (OR = 0.39). About 95%-100% of patients completed therapy irrespective of the drug regimen. At least one adverse effect occurred in 10.9%-36.3% and most of them were mild. No treatment related deaths have been reported.
CONCLUSION We documented very high effectiveness and a good safety profile across all DAA regimens. Positive predictors of SVR were female sex, absence of decompensated cirrhosis at baseline and higher platelet count while HIV coinfection reduced the effectiveness.
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Affiliation(s)
| | - Michał Brzdęk
- Department of Infectious Diseases, Jan Kochanowski University, Kielce 25-317, Poland
| | - Jerzy Jaroszewicz
- Department of Infectious Diseases and Hepatology, Medical University of Silesia, Katowice 40-055, Poland
| | | | - Beata Lorenc
- Pomeranian Center of Infectious Diseases, Medical University Gdańsk, Gdańsk 80-214, Poland
| | - Jakub Klapaczyński
- Department of Internal Medicine and Hepatology, Central Clinical Hospital of the Ministry of Internal Affairs and Administration, Warszawa 00-241, Poland
| | - Włodzimierz Mazur
- Clinical Department of Infectious Diseases, Medical University of Silesia, Chorzów 41-500, Poland
| | | | - Marek Sitko
- Department of Infectious and Tropical Diseases, Jagiellonian University, Kraków 31-088, Poland
| | - Hanna Berak
- Hospital for Infectious Diseases, Hospital for Infectious Diseases, Warszawa 02-091, Poland
| | - Justyna Janocha-Litwin
- Department of Infectious Diseases and Hepatology, Medical University Wrocław, Wrocław 50-367, Poland
| | - Dorota Dybowska
- Department of Infectious Diseases and Hepatology, Faculty of Medicine, Nicolaus Copernicus University, Bydgoszcz 85-030, Poland
| | - Łukasz Supronowicz
- Department of Infectious Diseases and Hepatology, Medical University of Białystok, Białystok 15-089, Poland
| | - Rafał Krygier
- Infectious Diseases and Hepatology Outpatient Clinic, Gemini NZOZ, Żychlin 62-571, Poland
| | - Jolanta Citko
- Medical Practice of Infections, Regional Hospital, Olsztyn 10-561, Poland
| | - Anna Piekarska
- Department of Infectious Diseases and Hepatology, Medical University Łódź, Łódź 90-419, Poland
| | - Robert Flisiak
- Department of Infectious Diseases and Hepatology, Medical University of Białystok, Białystok 15-089, Poland
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Abdel Alem S, El Garhy N, El Khateeb E, Khalil M, Cordie A, Elsharkawy A, Fouad R, Esmat G, Abdelbary MS. Serial changes in renal indices in chronic HCV patients with and without HIV co-infection receiving sofosbuvir and tenofovir-based therapies. Trans R Soc Trop Med Hyg 2022; 117:285-296. [PMID: 36397681 DOI: 10.1093/trstmh/trac107] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/05/2022] [Revised: 10/23/2022] [Accepted: 10/28/2022] [Indexed: 11/19/2022] Open
Abstract
Abstract
Background
Sofosbuvir (SOF) is authorized for hepatitis C virus (HCV) patients. The nephrotoxicity of SOF on HCV mono-infected and HCV–human immunodeficiency virus (HIV) individuals receiving antiretroviral therapy (ART) remains controversial.
Methods
A prospective study including 159 HCV mono-infected and 124 HCV–HIV individuals (47 were ART naïve and 77 were tenofovir [TDF]-based ART) who presented with an estimated glomerular filtration rate (eGFR) ≥30 ml/min/1.73 m2 at baseline and were treated with SOF–daclatasvir for 12 weeks. The eGFR was estimated using the Chronic Kidney Disease Epidemiology Collaboration equation over the study period.
Results
HCV patients had a progressive decline in median levels of eGFR compared with HCV–HIV patients who were ART naïve and those receiving TDF-based ART during and after discontinuing SOF–DAC treatment (96, 109 and 114 at baseline vs 94, 117 and 108 at the end of treatment [EOT]) vs 95, 114 and 115 ml/min/1.73 m2 at 12 weeks after treatment [SVR12], respectively). Moreover, the rate of eGFR stage worsening was more pronounced in HCV mono-infected compared with HCV–HIV individuals who were ART naïve and those receiving TDF-based ART (21.4% vs 8.5% and 14.3% at EOT; 21.4% vs 2.1% and 6.5% at SVR12, respectively). Multivariable regression analysis showed that baseline variables were not independent predictors of eGFR stage worsening either at EOT or SVR12.
Conclusions
Because the changes in eGFR were minimal and not of clinical significance, and TDF was not associated with an increase in renal dysfunction, SOF-based direct-acting antivirals could be safely used in HCV mono-infected and HCV–HIV individuals, even in those on TDF-based ART.
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Affiliation(s)
- Shereen Abdel Alem
- Endemic Medicine and Hepatology Department, Faculty of Medicine, Cairo University , Cairo 11562 , Egypt
| | - Naeema El Garhy
- Endemic Medicine and Hepatology Department, Faculty of Medicine, Cairo University , Cairo 11562 , Egypt
| | - Engy El Khateeb
- Clinical and Chemical Pathology Department, Faculty of Medicine, Cairo University , Cairo 11562 , Egypt
| | - Mahmoud Khalil
- Infectious Disease Department, Imbaba Fever Hospital , Cairo 12651 , Egypt
| | - Ahmed Cordie
- Endemic Medicine and Hepatology Department, Faculty of Medicine, Cairo University , Cairo 11562 , Egypt
| | - Aisha Elsharkawy
- Endemic Medicine and Hepatology Department, Faculty of Medicine, Cairo University , Cairo 11562 , Egypt
| | - Rabab Fouad
- Endemic Medicine and Hepatology Department, Faculty of Medicine, Cairo University , Cairo 11562 , Egypt
| | - Gamal Esmat
- Endemic Medicine and Hepatology Department, Faculty of Medicine, Cairo University , Cairo 11562 , Egypt
| | - Mohammad Salah Abdelbary
- Endemic Medicine and Hepatology Department, Faculty of Medicine, Cairo University , Cairo 11562 , Egypt
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10
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Pes F, Onali S, Balestrieri C, Angioni G, Ortu F, Piano P, Lucia B, Scioscia R, Princic E, Bolliri AC, Casale M, Cola A, Conti M, Peddis L, Serra G, Vacca S, Loi M, Urru E, Murru C, Matta L, Del Giacco S, Babudieri S, Maida I, Chessa L. HCV treatment in Sardinian HIV-HCV coinfected patients: a real-life perspective study on safety, efficacy, and immune reconstitution. Expert Rev Anti Infect Ther 2022; 20:1509-1516. [PMID: 36173889 DOI: 10.1080/14787210.2022.2130893] [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: 12/15/2022]
Abstract
BACKGROUND HIV-HCV co-infected patients have long been considered difficult-to-treat. The introduction of direct-acting antivirals (DAAs) changed this paradigm.We evaluated the efficacy and safety of DAA-based regimens and the impact of DAAs-induced HCV clearance on the immunological status in HIV-HCV co-infected patients. RESEARCH DESIGN AND METHODS HIV patients starting HCV treatment with DAAs were included. Sustained virological response at 12 weeks after DAAs treatment (SVR12) was assessed. CD4+ and CD8+ blood cell count and CD4+/CD8+ ratio were recorded at baseline and six months post DAA treatment. We enrolled 201 patients, 76.1% males, median age 54 years, the most common genotypes 3 (29.8%) and 1a (29.4%), 40.3% with cirrhosis, 32.3% with prior interferon-based treatment. All patients were on antiretroviral treatment, 24.4% on methadone maintenance therapy and 22.6% on psychotropic drugs. RESULTS SVR12 was 98.4%, the most common side effects were pruritus (8.4%), headache (7.4%) and fatigue (5.9%). An increase in CD4+ and CD8+ cell count was observed six months after completion of DAAs treatment, in particular in patients with low CD4+ cell count at baseline. CONCLUSIONS DAAs treatment resulted in high SVR12 rates, was well tolerated and Increased CD4+ and CD8+, especially in patients with low CD4+ cell count at baseline.
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Affiliation(s)
- Francesco Pes
- Department of Medical Sciences and Public Health, University of Cagliari, Cagliari, Italy
| | - Simona Onali
- Department of Medical Sciences and Public Health, University of Cagliari, Cagliari, Italy
| | - Cinzia Balestrieri
- Liver Unit, Department of Internal Medicine, University Hospital of Cagliari, Cagliari, Italy
| | | | - Francesco Ortu
- Immunology Unit, Department of Internal Medicine, University Hospital of Cagliari, Cagliari, Italy
| | - Paola Piano
- Immunology Unit, Department of Internal Medicine, University Hospital of Cagliari, Cagliari, Italy
| | - Barca Lucia
- Department of Medical Sciences and Public Health, University of Cagliari, Cagliari, Italy
| | - Rosetta Scioscia
- Department of Medical Sciences and Public Health, University of Cagliari, Cagliari, Italy
| | - Elija Princic
- Department of Clinical and Experimental Medicine, University of Sassari, Sassari, Italy
| | | | - Michele Casale
- Liver Unit, Department of Internal Medicine, University Hospital of Cagliari, Cagliari, Italy
| | - Alessandra Cola
- Liver Unit, Department of Internal Medicine, University Hospital of Cagliari, Cagliari, Italy
| | - Maria Conti
- Liver Unit, Department of Internal Medicine, University Hospital of Cagliari, Cagliari, Italy
| | - Lorenza Peddis
- Department of Medical Sciences and Public Health, University of Cagliari, Cagliari, Italy
| | - Giancarlo Serra
- Liver Unit, Department of Internal Medicine, University Hospital of Cagliari, Cagliari, Italy
| | - Stefano Vacca
- Department of Medical Sciences and Public Health, University of Cagliari, Cagliari, Italy
| | - Martina Loi
- Department of Medical Sciences and Public Health, University of Cagliari, Cagliari, Italy
| | - Enrico Urru
- Department of Medical Sciences and Public Health, University of Cagliari, Cagliari, Italy
| | - Claudia Murru
- Department of Medical Sciences and Public Health, University of Cagliari, Cagliari, Italy
| | - Laura Matta
- Department of Medical Sciences and Public Health, University of Cagliari, Cagliari, Italy
| | - Stefano Del Giacco
- Department of Medical Sciences and Public Health, University of Cagliari, Cagliari, Italy.,Immunology Unit, Department of Internal Medicine, University Hospital of Cagliari, Cagliari, Italy
| | - Sergio Babudieri
- Department of Clinical and Experimental Medicine, University of Sassari, Sassari, Italy
| | - Ivana Maida
- Department of Clinical and Experimental Medicine, University of Sassari, Sassari, Italy
| | - Luchino Chessa
- Department of Medical Sciences and Public Health, University of Cagliari, Cagliari, Italy.,Liver Unit, Department of Internal Medicine, University Hospital of Cagliari, Cagliari, Italy
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11
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Morsica G, Galli L, Messina E, Castagna A, Bagaglio S, Salpietro S, Liviana DT, Uberti-Foppa C, Hasson H. Risk of HIV viral rebound in HIV infected patients on direct acting antivirals (DAAs) treatment for HCV. PLoS One 2022; 17:e0262917. [PMID: 35113890 PMCID: PMC8812874 DOI: 10.1371/journal.pone.0262917] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/04/2021] [Accepted: 01/07/2022] [Indexed: 12/27/2022] Open
Abstract
BACKGROUND The dynamic of HIV-viral load (VL) remains poorly investigated in HIV/HCV patients under direct acting antivirals (DAAs). METHODS We retrospectively evaluated HIV-VL at baseline (BL) during and up to 24 weeks post-DAAs in a cohort of 305 HIV-1/HCV patients, on ART and with no HIV virological failure (VF) in the 6 months before treatment with DAAs; during the period of observation VF was defined as confirmed VL≥50 copies/mL; virological blips (VB, transient, not confirmed, VL ≥50 copies/mL). Stepwise Cox regression models were fitted to estimate adjusted hazard ratios (aHR) of VF. RESULTS Fifteen VF occurred in 13 patients over 187 person-years of follow-up (PYFU): incidence rate (IR) of 8.0 per 100-PYFU (95% CI = 4.0-12.1); 29 VBs were detected in 26 patients over 184 PYFU: IR = 15.8 per 100-PYFU (95% CI = 10.0-21.5). The most prominent factor associated with VF was the presence of BL HIV residual viremia (RV = HIV-RNA detectable but not precisely quantifiable) [aHR = 12.26 (95% CI = 3.74-40.17), P<0.0001]. Other factors were ≥1 VBs in the 6 months before DAAs [aHR = 6.95 (95% CI = 1.77-27.37) P = 0.006] number of ART regimens failed before DAAs initiation [aHR (per more regimen) = 1.22 (95% CI = 1.04-1.42), P = 0.012] and age [aHR (per year older) = 1.16 (95% CI = 1.04-1.29), P = 0.010]. CONCLUSIONS Our findings underline the importance for close monitoring HIV-VL in selected patients. Whether this phenomenon is triggered by the rapid clearance of HCV remains to be established.
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Affiliation(s)
- Giulia Morsica
- Division of Infectious Diseases, IRCCS San Raffaele Scientific Institute, Milan, Italy
| | - Laura Galli
- Division of Infectious Diseases, IRCCS San Raffaele Scientific Institute, Milan, Italy
| | - Emanuela Messina
- Division of Infectious Diseases, IRCCS San Raffaele Scientific Institute, Milan, Italy
| | - Antonella Castagna
- Division of Infectious Diseases, IRCCS San Raffaele Scientific Institute, Milan, Italy
- Vita-Salute University, Milan, Italy
| | - Sabrina Bagaglio
- Division of Infectious Diseases, IRCCS San Raffaele Scientific Institute, Milan, Italy
| | - Stefania Salpietro
- Division of Infectious Diseases, IRCCS San Raffaele Scientific Institute, Milan, Italy
| | - Della Torre Liviana
- Division of Infectious Diseases, IRCCS San Raffaele Scientific Institute, Milan, Italy
| | - Caterina Uberti-Foppa
- Division of Infectious Diseases, IRCCS San Raffaele Scientific Institute, Milan, Italy
- Vita-Salute University, Milan, Italy
| | - Hamid Hasson
- Division of Infectious Diseases, IRCCS San Raffaele Scientific Institute, Milan, Italy
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12
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Zarębska-Michaluk D, Jaroszewicz J, Parfieniuk-Kowerda A, Pawłowska M, Janczewska E, Berak H, Janocha-Litwin J, Klapaczyński J, Tomasiewicz K, Piekarska A, Krygier R, Citko J, Tronina O, Dobrowolska K, Flisiak R. Pangenotypic and Genotype-Specific Antivirals in the Treatment of HCV Genotype 4 Infected Patients with HCV Monoinfection and HIV/HCV Coinfection. J Clin Med 2022; 11:jcm11020389. [PMID: 35054088 PMCID: PMC8781964 DOI: 10.3390/jcm11020389] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/28/2021] [Revised: 12/29/2021] [Accepted: 01/11/2022] [Indexed: 02/07/2023] Open
Abstract
The introduction of the direct-acting antivirals (DAA) has substantially improved the effectiveness of the therapy in patients with chronic hepatitis C. We aimed to compare the efficacy of pangenotypic and genotype-specific DAA in the cohort of genotype (GT) four patients with HCV monoinfection and HIV coinfection. A total of 662 GT4-infected patients treated in 2015–2020—of whom 168 (25.3%) were coinfected with HIV, selected from the retrospective EpiTer-2 database—were enrolled in the analysis. Among HIV-coinfected patients, 54% (90) were treated with genotype-specific regimens and 46% (78) with pangenotypic options, while among HCV-monoinfected patients, the rates were 72% and 28%, respectively. Significantly higher rate of males (67.9% vs. 57.7%, p = 0.01), a lower rate of liver cirrhosis (10.2% vs. 18.1%, p = 0.02), and higher of treatment-naïve patients (87.5% vs. 76.7%, p = 0.003) were documented in the HIV coinfected population. The overall sustained virologic response after exclusion of non-virologic failures was achieved in 98% with no significant difference between HIV-positive and HIV-negative patients, 96.2% vs. 98.5%, respectively. While the genotype-specific regimens resulted in a similar cure rate regardless of the HIV status, the pangenotypic options were more efficacious in patients with HCV monoinfection (99.3% vs. 94.4%, p = 0.05). Hereby, we demonstrated the high effectiveness and good safety profile of the DAA therapy in the population of HCV GT4 infected patients with HIV coinfection supporting the current recommendations to treat HCV/HIV coinfected patients with the same options as those with HCV monoinfection.
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Affiliation(s)
- Dorota Zarębska-Michaluk
- Department of Infectious Diseases, Jan Kochanowski University Kielce, 25-516 Kielce, Poland
- Correspondence: (D.Z.-M.); (R.F.)
| | - Jerzy Jaroszewicz
- Department of Infectious Diseases and Hepatology, Medical University of Silesia in Katowice, 40-055 Katowice, Poland;
| | - Anna Parfieniuk-Kowerda
- Department of Infectious Diseases and Hepatology, Medical University of Białystok, 15-540 Białystok, Poland;
| | - Małgorzata Pawłowska
- Department of Infectious Diseases and Hepatology, Ludwik Rydygier Collegium Medicum, Bydgoszcz Faculty of Medicine Nicolaus Copernicus University in Toruń, 85-030 Bydgoszcz, Poland;
| | - Ewa Janczewska
- Faculty of Health Sciences in Bytom, Department of Basic Medical Sciences, Medical University of Silesia, ID Clinic, Hepatology Outpatient Department, 41-902 Bytom, Poland;
| | - Hanna Berak
- Hospital for Infectious Diseases in Warszawa, 02-091 Warszawa, Poland;
| | - Justyna Janocha-Litwin
- Department of Infectious Diseases and Hepatology, Medical University Wrocław, 50-367 Wrocław, Poland;
| | - Jakub Klapaczyński
- Department of Internal Medicine and Hepatology, Central Clinical Hospital of the Ministry of Internal Affairs and Administration, 02-507 Warszawa, Poland;
| | - Krzysztof Tomasiewicz
- Department of Infectious Diseases, Medical University of Lublin, 20-059 Lublin, Poland;
| | - Anna Piekarska
- Department of Infectious Diseases and Hepatology, Medical University of Łódź, 90-419 Łódź, Poland;
| | - Rafał Krygier
- Outpatients Hepatology Department, State University of Applied Sciences, 62-510 Konin, Poland;
| | - Jolanta Citko
- Medical Practice of Infections, Regional Hospital, 10-561 Olsztyn, Poland;
| | - Olga Tronina
- Department of Transplantation Medicine, Nephrology, and Internal Diseases, Medical University of Warsaw, 02-006 Warszawa, Poland;
| | | | - Robert Flisiak
- Department of Infectious Diseases and Hepatology, Medical University of Białystok, 15-540 Białystok, Poland;
- Correspondence: (D.Z.-M.); (R.F.)
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13
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Ivantes CAP, Silva BCD, Acosta GG, Tawil FBNE, Nisihara R. NON-ADHERENCE TO HEPATITIS C TREATMENT: A BRAZILIAN REPORT. ARQUIVOS DE GASTROENTEROLOGIA 2021; 58:456-460. [PMID: 34909850 DOI: 10.1590/s0004-2803.202100000-83] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Received: 03/09/2021] [Accepted: 05/03/2021] [Indexed: 11/21/2022]
Abstract
BACKGROUND In Brazil, since 2015, the treatment of hepatitis C is provided by SUS (Public Health System) with direct-acting antiviral (DAA). OBJECTIVE To describe the rate of non-adherence patients to hepatitis C treatment by DAA, investigating the epidemiological data in a large database from Curitiba, Brazil. METHODS Retrospective study with patients treated between January 2015 and June 2019. Patients were considered adherent when received all medication doses during their treatment. The following data were evaluated: gender, age, type of treatment, period of treatment, presence of diabetes or HIV, previous therapy, originated from SUS or private medicine, fibrosis grade and HCV genotype. RESULTS 1248 patients (56.8% males) were studied and 102/1248 (8.2%) were non-adherent to treatment. Age or gender not influenced significantly; 10.2% patients from SUS and 3.7% individuals from private medicine were non-adherent (P<0.0001; OR=2.9; CI95%=1.6-9.1); 13.1% patients were co-infected with HIV and among them, 15.9% abandoned treatment. Individuals without co-infection presented 7.0% of non-adherence (P<0.0001; OR=2.5; CI=1.5-4.1). All the other variables showed no differences in the adhesion rate. CONCLUSION Our study showed that 8.2% of patients were non-adherent to HCV treatment, and that patients from the Public Health System and co-infected with HIV were significantly less adherent.
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Affiliation(s)
| | | | | | | | - Renato Nisihara
- Universidade Positivo, Departamento de Medicina, Curitiba, PR, Brasil
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14
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Abdelaziz H, Omar H, Khalil M, Cordie A, Mohamed R, AbdAllah M, Abdel Maksoud MH, El Garhy N, Ali L, El Serafy M, Esmat G, Doss W. Real-life experience of treating HCV co-infection among HIV-infected population in Egypt: single-center experience. Expert Rev Anti Infect Ther 2021; 20:789-795. [PMID: 34751609 DOI: 10.1080/14787210.2022.2004117] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/19/2022]
Abstract
BACKGROUND Liver disease has emerged as a leading cause of death among PLHIV coinfected with HCV. METHODS A retrospective study involving all HCV viremic patients coinfected with HIV who presented to HCV/HIV multidisciplinary clinics located at Embaba fever hospital. Patients were assigned to receive DAAs according to the national treatment guidelines. The primary endpoint was SVR12. RESULTS Of the 519 patients enrolled, 38.73% LTFU; either not initiated (n = 170) or did not complete the treatment (n = 31). The main identified reasons behind LTFU were schedule conflict (19%) or hospitalization (13%). Among 318 patients who completed their DAAs course, nine patients had a relapse after the end of treatment and 97% had attained SVR12. There were significant differences among different virological response groups in baseline factors including smoking (p = 0.005), history of dental procedure (p = 0.007), CD4 count (p = 0.007), and HIV viral load (p = <0.001). Among responders (n = 309), there was a significant reduction of baseline hemoglobin and significant improvement of baseline platelets (p = 0.005) at on-treatment week 8. Baseline necro-inflammatory markers showed significant improvement across follow-up time points (p < 0.001). CONCLUSIONS DAAs are an effective and safe choice to treat HCV in PLHIV. Social stigma could be a major cause for lacking adherence to follow-up visits.Abbreviations: ALT: Alanine Aminotransferase; ARV: Antiretroviral treatment; AST: Aspartate Aminotransferase; DAAs: Direct acting antivirals; ARVs: antiretroviral therapy; EMR: Eastern Mediterranean region; HCV: Hepatitis C virus; kPa: Kilopascal; LTFU: Patient lost to follow up; NCCVH: The National Committee for Control of Viral Hepatitis; PWID: People who inject drugs; SVR: Sustained virological response;UNAIDS: The Joint United Nations Programme on HIV/AIDS.
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Affiliation(s)
- Hossam Abdelaziz
- Endemic Medicine and Hepatology Department, Faculty of Medicine, Cairo University, Giza, Egypt.,Hepatology Department, Faculty of Medicine, Ain Shams University, Cairo, Egypt
| | - Heba Omar
- Endemic Medicine and Hepatology Department, Faculty of Medicine, Cairo University, Giza, Egypt
| | - Mahmoud Khalil
- Infectious Disease Department, National Hepatology and Tropical Medicine Research Institute, Cairo, Egypt
| | - Ahmed Cordie
- Endemic Medicine and Hepatology Department, Faculty of Medicine, Cairo University, Giza, Egypt.,Kasr Alainy Hiv and Viral Hepatitis Fighting Group Cairo Egypt
| | - Rahma Mohamed
- Endemic Medicine and Hepatology Department, Faculty of Medicine, Cairo University, Giza, Egypt.,Kasr Alainy Hiv and Viral Hepatitis Fighting Group Cairo Egypt
| | - Mohamed AbdAllah
- Medical Research Division, National Research Center, Cairo, Egypt
| | | | - Naeema El Garhy
- Endemic Medicine and Hepatology Department, Faculty of Medicine, Cairo University, Giza, Egypt
| | - Lamiaa Ali
- Endemic Medicine and Hepatology Department, Faculty of Medicine, Cairo University, Giza, Egypt
| | - Magdy El Serafy
- Endemic Medicine and Hepatology Department, Faculty of Medicine, Cairo University, Giza, Egypt
| | - Gamal Esmat
- Endemic Medicine and Hepatology Department, Faculty of Medicine, Cairo University, Giza, Egypt
| | - Wahid Doss
- Endemic Medicine and Hepatology Department, Faculty of Medicine, Cairo University, Giza, Egypt
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15
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Yunihastuti E, Hariyanto R, Sulaiman AS, Harimurti K. Hepatitis C continuum of care: Experience of integrative hepatitis C treatment within a human immunodeficiency virus clinic in Indonesia. PLoS One 2021; 16:e0256164. [PMID: 34383853 PMCID: PMC8360535 DOI: 10.1371/journal.pone.0256164] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/15/2021] [Accepted: 08/01/2021] [Indexed: 12/24/2022] Open
Abstract
INTRODUCTION Direct-acting antiviral drugs (DAAs) have changed the paradigm of hepatitis C therapy for both HCV/HIV co-infected and HCV mono-infected patients. We aimed to describe the HCV continuum of care of HIV-infected patients treated in an HIV clinic after a free DAA program in Indonesia and identify factors correlated with sofosbuvir-daclatasvir (SOF-DCV) treatment failure. METHODS We did a retrospective cohort study of adult HIV/HCV co-infected patients under routine HIV-care from November 2019 to April 2020 in the HIV integrated clinic of Cipto Mangunkusumo Hospital, Jakarta, Indonesia. We evaluated some factors correlated with sofosbuvir-daclatasvir treatment failure: gender, diabetes mellitus, previous IFN failure, cirrhosis, concomitant ribavirin use, high baseline HCV-RNA, and low CD4 cell count. RESULTS AND DISCUSSION Overall, 640 anti-HCV positive patients were included in the study. Most of them were male (88.3%) and former intravenous drug users (76.6%) with a mean age of 40.95 (SD 4.60) years old. Numbers and percentages for the stages of the HCV continuum of care were as follows: HCV-RNA tested (411; 64.2%), pre-therapeutic evaluation done (271; 42.3%), HCV treatment initiated (210; 32.8%), HCV treatment completed (207; 32.2%), but only 178 of these patients had follow-up HCV-RNA tests to allow SVR assessment; and finally SVR12 achieved (178; 27.8%). For the 184 who completed SOF-DCV treatment, SVR12 was achieved by 95.7%. In multivariate analysis, diabetes mellitus remained a significant factor correlated with SOF-DCV treatment failure (adjusted RR 17.0, 95%CI: 3.28-88.23, p = 0.001). CONCLUSIONS This study found that in the HCV continuum of care for HIV/HCV co-infected patients, gaps still exist at all stages. As the most commonly used DAA combination, sofosbuvir daclatasvir treatment proved to be effective and well-tolerated in HIV/HCV co-infected patients. Diabetes mellitus was significant factor correlated with not achieving SVR12 in this population.
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Affiliation(s)
- Evy Yunihastuti
- Department Internal Medicine, Faculty of Medicine Universitas Indonesia/Cipto Mangunkusumo Hospital, Jakarta, Indonesia
- HIV Integrated Clinic, Cipto Mangunkusumo Hospital, Jakarta, Indonesia
| | - Rahmat Hariyanto
- Department Internal Medicine, Faculty of Medicine Universitas Indonesia/Cipto Mangunkusumo Hospital, Jakarta, Indonesia
| | - Andri Sanityoso Sulaiman
- Department Internal Medicine, Faculty of Medicine Universitas Indonesia/Cipto Mangunkusumo Hospital, Jakarta, Indonesia
| | - Kuntjoro Harimurti
- Department Internal Medicine, Faculty of Medicine Universitas Indonesia/Cipto Mangunkusumo Hospital, Jakarta, Indonesia
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Cordie A, Elsharkawy A, Abdel Alem S, Meshaal S, El Akel W, Abdellatif Z, Kamal W, Al Askalany M, Kamel S, Abdel Aziz H, Kandeel A, Esmat G. Sustained virologic response and changes in liver fibrosis parameters following 12-wk administration of generic sofosbuvir and daclatasvir in HIV/HCV-coinfected patients with HCV genotype 4 infection. Trans R Soc Trop Med Hyg 2021; 114:232-240. [PMID: 31925434 DOI: 10.1093/trstmh/trz120] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/11/2019] [Revised: 09/19/2019] [Accepted: 10/30/2019] [Indexed: 12/13/2022] Open
Abstract
BACKGROUND Novel direct-acting antiviral agents have shown great efficacy and tolerability in HCV-monoinfected patients. However, data are lacking regarding their efficacy and safety in HIV/HCV-genotype (GT) 4-coinfected patients. METHODS A single-centre, prospective study including HIV/HCV-GT 4-coinfected patients who were treated with sofosbuvir and daclatasvir (SOF/DCV) was conducted for 12 wk. Sustained virological response (SVR) at week 12 post-treatment (SVR12), adverse events (AEs) and changes in liver stiffness measurement (LSM) at SVR12 in comparison with baseline were evaluated. RESULTS SVR12 was achieved in 46 of 50 patients (92%). No significant difference in SVR12 was noticed among patients who received antiretroviral therapy (ART) regimens compared with those who did not receive ART regimens or between those with insignificant fibrosis (<F2) and those with significant fibrosis (≥F2) (p=0.9 and p=0.3, respectively). AEs occurred in 45 (90%) patients. The most frequent AEs were fatigue, headache and nausea. No treatment-related serious AEs or deaths were reported. HIV control was not compromised. LSM, fibrosis 4 score and aspartate aminotransferase-to-platelet ratio index showed a significant decrease at SVR12 when compared with baseline (p=0.0004, p=0.0003 and p<0.0001, respectively). Logistic regression analysis showed no association between baseline variables and SVR12 while significant fibrosis (≥F2) was the only baseline variable that was significantly associated with improvement of LSM at SVR12. CONCLUSION SOF/DCV achieved a high SVR12 and was well-tolerated in HIV/HCV-GT 4-coinfected patients.
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Affiliation(s)
- Ahmed Cordie
- Endemic Medicine and Hepatology Department, Faculty of Medicine, Cairo University, Cairo 11562, Egypt
| | - Aisha Elsharkawy
- Endemic Medicine and Hepatology Department, Faculty of Medicine, Cairo University, Cairo 11562, Egypt
| | - Shereen Abdel Alem
- Endemic Medicine and Hepatology Department, Faculty of Medicine, Cairo University, Cairo 11562, Egypt
| | - Safa Meshaal
- Clinical pathology Department, Faculty of Medicine, Cairo University, Cairo 11562, Egypt
| | - Wafaa El Akel
- Endemic Medicine and Hepatology Department, Faculty of Medicine, Cairo University, Cairo 11562, Egypt
| | - Zeinab Abdellatif
- Endemic Medicine and Hepatology Department, Faculty of Medicine, Cairo University, Cairo 11562, Egypt
| | - Walid Kamal
- Preventive sector, Ministry of Health and Population, Cairo 11516, Egypt
| | - Mahmoud Al Askalany
- Imbaba Fever Hospital, Ministry of Health and Population, Cairo 12651, Egypt
| | - Sherif Kamel
- Imbaba Fever Hospital, Ministry of Health and Population, Cairo 12651, Egypt
| | - Hossam Abdel Aziz
- Department of Hepatology, Faculty of Medicine, Ain Shams University, Cairo 11591, Egypt
| | - Amr Kandeel
- Preventive sector, Ministry of Health and Population, Cairo 11516, Egypt
| | - Gamal Esmat
- Endemic Medicine and Hepatology Department, Faculty of Medicine, Cairo University, Cairo 11562, Egypt
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17
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Mohamed IELK, EL-Saeed KM, Al-Sadik MH, Anwar CA. Safety and efficacy of directly acting antivirals (sofosbuvir and daclatasvir) in treatment of chronic HCV in HIV-HCV co-infected Egyptian patients. EGYPTIAN LIVER JOURNAL 2021. [DOI: 10.1186/s43066-021-00089-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/10/2022] Open
Abstract
Abstract
Background
Cure of chronic hepatitis C (HCV) in HIV/HCV co-infected patients is a priority due to their increased risk of complications. Daclatasvir and sofosbuvir treatment regimens with or without ribavirin are considered an important chance for better HCV treatment in patients with HIV/HCV co-infection. This study aimed at the assessment of safety and efficacy of sofosbuvir-daclatasvir treatment regimens in HIV/HCV co-infected Egyptian patients.
Results
Thirty HIV/HCV co-infected adult patients were included. All patients completed the study duration without major problems or drug interactions, HCV PCR was negative for all patients at the end of treatment, yet 12 weeks after ending treatment, only one patient (3.33%) had HCV relapse.
Liver enzymes showed a significant decrease by the end of treatment and 12 weeks after end of treatment in comparison with their values before treatment (P-value = 0.0001). CD4 counts as well showed significant increase. There was non-significant change in serum albumin, total bilirubin, alfa fetoprotein, complete blood count (CBC), coagulation profile, random blood sugar, or serum creatinine. Ultrasonographic findings did not show significant difference.
Conclusion
Combination of daclatasvir and sofosbuvir have showed 96.67% sustained virologic response at 12 weeks after treatment (SVR 12) among HIV/HCV co-infected patients, with a good safety profile. Moreover, the treated patients showed a significant increase in CD4 lymphocytic count.
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The Impact of Markers of HIV Infection on Change in Liver Stiffness in People With HIV and Hepatitis C Virus Co-infection After Treatment and Cure of Hepatitis C. J Acquir Immune Defic Syndr 2021; 85:e81-e89. [PMID: 32842055 DOI: 10.1097/qai.0000000000002487] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/23/2022]
Abstract
BACKGROUND Markers of HIV disease severity are associated with increased liver fibrosis in HIV/Hepatitis C virus (HCV) co-infected individuals. HCV treatment may reverse liver fibrosis, but evidence among HIV/HCV-co-infected populations and the impact of HIV parameters on fibrosis regression is limited. We aimed to assess the influence of surrogate markers of HIV-infection and other determinants of liver stiffness before HCV treatment and changes after HCV cure in people living with HIV. METHODS We used data from an HCV treatment implementation study aiming for HCV micro-elimination among gay and bisexual men with HIV in Melbourne, Australia (co-EC Study). We obtained liver stiffness measurements (LSM) before and after direct-acting antiviral treatment using transient elastography (FibroScan). Linear mixed models were used to evaluate determinants of pretreatment LSM and changes in LSM following cure with duration in years between pre- and post-LSM assessment as main exposure variable. RESULTS At least one LSM was available in 173 participants, and 98 participants had 2 LSMs. Median pre- and post-treatment LSMs were 5.7 and 5.1 kPa, respectively. Median time between transient elastography measurements was 1.3 years (interquartile range = 0.9-2.1). In multivariable analysis, longer duration of known HIV infection, a lower CD4 and CD8 T-cell count and hazardous alcohol consumption were associated with higher LSM values before treatment initiation. Successfully treated patients had a 6% (95% confidence interval = -10% to -2%) annual decrease (0.34 kPa predicted decrease) in LSM following cure. Changes in LSM values did not depend on any of the pretreatment HIV markers or other factors. CONCLUSION Low levels of liver stiffness were observed before treatment initiation and a small decrease (6%) in LSM following HCV cure in people living with HIV. No clear predictors affecting change in LSM following cure were found in this study, including markers of HIV infection. However, markers of advanced HIV immunodeficiency and hazardous alcohol consumption remained associated with higher LSM values even after HCV cure.
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Jatt LP, Gandhi MM, Guo R, Sukhija-Cohen A, Bhattacharya D, Tseng CH, Chew KW. Barriers to hepatitis C direct-acting antiviral therapy among HIV/hepatitis C virus-coinfected persons. J Gastroenterol Hepatol 2021; 36:1095-1102. [PMID: 32840904 PMCID: PMC7904967 DOI: 10.1111/jgh.15228] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/02/2020] [Revised: 08/11/2020] [Accepted: 08/13/2020] [Indexed: 12/13/2022]
Abstract
BACKGROUND AND AIM Direct-acting antivirals (DAAs) have increased hepatitis C virus (HCV) treatment opportunities for vulnerable HIV/HCV coinfected persons. The aim of this study was to identify the frequency of and potential barriers to DAA prescription in HIV/HCV patients during the first few years of DAA availability in the United States. METHODS The AIDS Healthcare Foundation electronic medical record system was queried to identify all HCV viremic HIV-infected patients in care at AIDS Healthcare Foundation Healthcare centers in January 2015-August 2017 and compare characteristics by receipt of a DAA prescription. Multivariate logistic regression analyses were conducted to examine factors associated with DAA prescription. RESULTS Of 826 eligible patients, 355 (43%) were prescribed a DAA; among those not prescribed a DAA, 301 (64%) had well-controlled HIV (HIV RNA ≤ 200 copies per mL). In multivariate logistic regression analysis, patients with a history of substance use (odds ratio [OR], 0.51 [95% confidence interval 0.35-0.73]) or on select HIV antiretroviral regimens were less likely to be prescribed a DAA. Those who had well-controlled HIV (OR, 5.03 [3.06-8.27]), CD4 + T cell count >200 cells per mm3 (OR, 1.85 [1.04-3.30]), estimated glomerular filtration rate >60 mL/min/1.73 m2 (OR, 3.32 [1.08-10.15]), or established care prior to January 2015 (OR, 1.57 [1.08-2.29] were more likely to be prescribed a DAA. CONCLUSIONS In addition to lack of HIV suppression, select antiretroviral regimens, substance use, and kidney disease appeared to limit DAA prescription in the early interferon-free DAA era. Many were not prescribed DAAs despite HIV suppression. Further research is needed to determine if the observed associations persist today.
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Affiliation(s)
- Lauren P Jatt
- David Geffen School of Medicine, UCLA, Los Angeles, California, USA
| | - Malini M Gandhi
- Division of Infectious Diseases, Department of Medicine, David Geffen School of Medicine, UCLA, Los Angeles, California, USA
| | - Rong Guo
- Division of General Internal Medicine and Health Services Research, David Geffen School of Medicine, UCLA, Los Angeles, California, USA
| | - Adam Sukhija-Cohen
- Public Health Division, AIDS Healthcare Foundation, Los Angeles, California, USA
| | - Debika Bhattacharya
- Division of Infectious Diseases, Department of Medicine, David Geffen School of Medicine, UCLA, Los Angeles, California, USA
| | - Chi-Hong Tseng
- Division of General Internal Medicine and Health Services Research, David Geffen School of Medicine, UCLA, Los Angeles, California, USA
| | - Kara W Chew
- Division of Infectious Diseases, Department of Medicine, David Geffen School of Medicine, UCLA, Los Angeles, California, USA
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Fabbiani M, Lombardi A, Colaneri M, Del Poggio P, Perini P, D'Ambrosio R, Degasperi E, Dibenedetto C, Giorgini A, Pasulo L, Maggiolo F, Castelli F, Brambilla P, Spinelli O, Re T, Lleo A, Rumi M, Uberti-Foppa C, Soria A, Aghemo A, Lampertico P, Baiguera C, Schiavini M, Fagiuoli S, Bruno R. High rates of sustained virological response despite premature discontinuation of directly acting antivirals in HCV-infected patients treated in a real-life setting. J Viral Hepat 2021; 28:558-568. [PMID: 33306247 DOI: 10.1111/jvh.13454] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/23/2020] [Revised: 08/21/2020] [Accepted: 11/18/2020] [Indexed: 01/08/2023]
Abstract
In routine clinical practice, hepatitis C virus-infected patients can prematurely discontinue the prescribed regimen for several reasons. The aim of our study was to investigate sustained virological response (SVR12) rates in patients who prematurely discontinued directly acting antiviral (DAA) regimens and to assess the shortest effective duration of DAA able to lead to SVR12. We retrospectively collected the SVR rates of patients, registered in the NAVIGATORE-Lombardia Network database from January 2015, who discontinued DAAs before the predefined end of treatment. Overall, we included 365 patients, males were the majority (213, 58.4%), mean age was 60.5 years, and 53 (14.5%) patients were HIV-co-infected. Liver cirrhosis was observed in 251 (68.8%) subjects, and the most represented genotypes were 1b (n = 168, 46%) and 3 (n = 59, 16.2%). DAA was discontinued a median of 1 (IQR 1-4) weeks before the predefined EOT, with 164 (44.9%) patients stopping DAAs at least 2 weeks before the planned schedule. In patients with F0-F3 liver fibrosis, lower rates of SVR12 were observed in patients treated for <4 weeks: 50% (n = 2/4) vs. 99.1% (n = 109/110) for ≥4 weeks, p = 0.003. In patients with liver cirrhosis, lower rates of SVR12 were observed in patients treated <8 weeks: 83.3% (n = 25/30) vs. 94.6% (n = 209/221) for ≥8 weeks, p = 0.038. Despite premature discontinuation of DAA, high SVR12 rates were observed in a real-life setting for treatment lasting at least 4 weeks in patients with liver fibrosis F0-F3 and 8 weeks in those with liver cirrhosis. On this basis, feasibility of reducing DAA treatment duration should be explored in randomized clinical trials.
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Affiliation(s)
- Massimiliano Fabbiani
- U.O. Malattie Infettive e Tropicali, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy.,UOC Malattie Infettive e Tropicali, Azienda Ospedaliero-Universitaria Senese, Siena, Italy
| | - Andrea Lombardi
- U.O. Malattie Infettive e Tropicali, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy
| | - Marta Colaneri
- U.O. Malattie Infettive e Tropicali, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy
| | | | - Paolo Perini
- Divisione di Medicina, Policlinico San Pietro, Bergamo, Italy
| | - Roberta D'Ambrosio
- Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico, Milan, Italy.,UOC Gastroenterologia ed Epatologia, CRC 'AM e A Migliavacca' per lo studio e la cura delle malattie del fegato, Milan, Italy
| | - Elisabetta Degasperi
- Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico, Milan, Italy.,UOC Gastroenterologia ed Epatologia, CRC 'AM e A Migliavacca' per lo studio e la cura delle malattie del fegato, Milan, Italy
| | - Clara Dibenedetto
- Unità di Epatologia e Gastroenterologia, Ospedale San Paolo, Milan, Italy
| | - Alessia Giorgini
- Unità di Epatologia e Gastroenterologia, Ospedale San Paolo, Milan, Italy
| | - Luisa Pasulo
- Unità di Gastroenterologia, ASST Papa Giovanni XXIII, Bergamo, Italy
| | - Franco Maggiolo
- U.O. Malattie Infettive, ASST Papa Giovanni XXIII, Bergamo, Italy
| | | | - Paola Brambilla
- U.O. Malattie Infettive, Istituti Ospitalieri, Cremona, Italy
| | | | - Tiziana Re
- U.O. Malattie Infettive, ASST Ovest Milanese, Legnano, Italy
| | - Ana Lleo
- Medicina Interna ed Epatologia, Humanitas Clinical and Research Center-IRCCS, Rozzano, Italy
| | - Mariagrazia Rumi
- U.O. Epatologia, Ospedale San Giuseppe Multimedica, Università degli Studi di Milano, Milan, Italy
| | - Caterina Uberti-Foppa
- Division of Infectious Diseases, Vita-Salute San Raffaele University Milan, Milan, Italy.,Division of Infectious Diseases, IRCCS San Raffaele Scientific Institute, Milan, Italy
| | - Alessandro Soria
- UO Malattie Infettive, Ospedale San Gerardo, ASST Monza, Monza, Italy
| | - Alessio Aghemo
- Medicina Interna ed Epatologia, Humanitas Clinical and Research Center-IRCCS, Rozzano, Italy
| | - Pietro Lampertico
- Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico, Milan, Italy.,UOC Gastroenterologia ed Epatologia, CRC 'AM e A Migliavacca' per lo studio e la cura delle malattie del fegato, Milan, Italy.,Università degli Studi di Milano, Milan, Italy
| | - Chiara Baiguera
- UO Malattie Infettive, ASST Grande Ospedale Metropolitano Niguarda, Milan, Italy
| | - Monica Schiavini
- Dipartimento di Malattie Infettive, Ospedale Luigi Sacco, Milan, Italy
| | - Stefano Fagiuoli
- Unità di Gastroenterologia, ASST Papa Giovanni XXIII, Bergamo, Italy
| | - Raffaele Bruno
- U.O. Malattie Infettive e Tropicali, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy
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Increased mortality in HIV/HCV-coinfected compared to HCV-monoinfected patients in the DAA era due to non-liver-related death. J Hepatol 2021; 74:37-47. [PMID: 32798585 DOI: 10.1016/j.jhep.2020.08.008] [Citation(s) in RCA: 18] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/20/2020] [Revised: 07/16/2020] [Accepted: 08/11/2020] [Indexed: 12/12/2022]
Abstract
BACKGROUND & AIMS Direct-acting antivirals (DAA) lead to high sustained virological response (SVR) rates and decrease the risk of disease progression. We compared SVR rates and all-cause, liver- and non-liver-related deaths, liver-related events, and non-liver-related cancers in HIV/HCV-coinfected and HCV-monoinfected participants from 2 French cohort studies after initiation of DAA treatment. METHODS Up to 4 HCV-monoinfected participants from the ANRS CO22 HEPATHER cohort were matched by age and sex to each HIV/HCV-coinfected patient from the ANRS CO13 HEPAVIH cohort; both are nationwide, prospective, multicentre, and observational. Participants were initiated on DAAs between March 2014 and December 2017. Cox proportional hazards models adjusted by age, sex, duration since HCV diagnosis, HCV transmission routes, HCV genotypes, cirrhosis, tobacco, alcohol consumption, and SVR (time dependent) were used. RESULTS A total of 592 HIV/HCV-coinfected and 2,049 HCV-monoinfected participants were included; median age was 53.3 years (inter-quartile range: 49.6-56.9) and 52.9 years (49.6; 56.7), 1,498 (73.1%) and 436 (73.6%) were men, and 159 (28.8%) and 793 (41.2%) had cirrhosis, respectively. SVR was observed in 92.9% and 94.6%, respectively. HIV coinfection was associated with higher risk of all-cause death (hazard ratio [HR] 1.93; 95% CI 1.01-3.69), non-liver-related death (HR 2.84; 95% CI 1.27-6.36), and non-liver-related cancer (HR 3.26; 95% CI 1.50-7.08), but not with liver-related-death (HR 1.04; 95% CI 0.34-3.15) or liver-related events (HR 0.66; 95% CI 0.31-1.44). CONCLUSIONS After DAA treatment, HIV-coinfected individuals had similar SVR rates and risk of liver-related deaths and events compared with HCV-monoinfected individuals, but had a higher risk of all-cause and non-liver-related deaths and non-liver-related cancers. LAY SUMMARY We compared the risk of several clinical events in participants infected by human immunodeficiency virus and hepatitis C virus with those infected with hepatitis C virus alone, matched on age and sex, after treatment with contemporary direct-acting antivirals. We found a higher risk of all-cause deaths, non-liver-related deaths, and non-liver-related cancers in participants coinfected with the human immunodeficiency virus and hepatitis C virus, and no differences for the risk of liver-related deaths or events.
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Efficacy and Tolerability of Daclatasvir/Sofosbuvir (Datex) in Patients with HIV-HCV Co-infection. ARCHIVES OF CLINICAL INFECTIOUS DISEASES 2020. [DOI: 10.5812/archcid.99952] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2022]
Abstract
Background: Treatment of hepatitis C virus (HCV) infection with direct-acting antiviral agents in patients with HCV/human immunodeficiency virus (HIV) co-infection remains controversial due to drug interactions with antiretroviral therapy (ART). Objectives: In this study, we assessed the efficacy and tolerability of daclatasvir/sofosbuvir (DCV/SOF) in patients with HIV-HCV co-infection in the real-life setting in Iran. Methods: A total of 44 patients with HCV-HIV co-infection (genotypes 1, 3, and 4) were treated with DCV/SOF±RBV (ribavirin) (dose-adjusted DCV for concomitant ART). Assessment of risk factors, sustained virologic response at 12 weeks after the end of treatment (SVR12), safety, and serum CD4 count was performed. Results: Most patients were male (95.2%). Four patients were HCV treatment-experienced cases, and 15 had cirrhosis or advanced fibrosis. The most common genotype was 3 (53.5%), followed by 1 (44.2%) and 4 (2.3%). HIV-1 RNA < 50 copies/mL and CD4 count > 250 cells/mm3 were observed in 81.8% and 79.1% of patients, respectively. The highest risk factor was a history of IV drug use (81.8%), followed by using a common syringe (77.3%) and tattooing (70.5%). All patients with or without cirrhosis (100%) completed the HCV treatment course and achieved SVR12. Also. 92.6% of patients on ART had CD4 count > 250 cells/mm3 at the end of treatment. The HCV treatment regimen was well-tolerated. Moreover, 15.9% of patients experienced adverse events (AEs), including anorexia, nausea, diarrhea, palpitations, and anxiety. No serious AEs or discontinuation due to AEs were reported. Conclusions: Our study showed excellent tolerability and efficacy of DCV/SOF±RBV in HIV-HCV co-infected patients with or without cirrhosis.
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Hepatitis C virus-microelimination program and patient trajectories after hepatitis C virus cure in an outpatient HIV clinical unit. Eur J Gastroenterol Hepatol 2020; 32:1212-1221. [PMID: 31851097 DOI: 10.1097/meg.0000000000001640] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Abstract
OBJECTIVE Treatment recommendations for hepatitis C now make no distinction between HIV/HCV-coinfected and HCV-monoinfected patients. The largest challenge remained lack of effective models to eliminate HCV in people living with HIV. We report the results of a microelimination program evaluating the possibility of eradicating HCV in an HIV-outpatient clinical unit within 12 months. METHODS This HCV-microelimination program began in February 2016 in an unit following approximately 1000 HIV-infected patients and combined screening and therapeutic components according to the French guideline. A nested cohort study evaluating the impact of HCV cure on different health outcomes was conducted through self-administered questionnaires and using generalized mixed models. RESULTS Among 601 patients eligible for HCV serological testing, 445 were evaluated, and two HCV acute infections were diagnosed. Among the 151 patients eligible for HCV RNA quantification, 119 were evaluated, and one reinfection with HCV was diagnosed. Among the 110 patients eligible for direct-acting antiviral treatment, 51 (46.4%) initiated treatment within the 12 months program, and 35 (31.8%) after. Sustained virologic response (SVR) rate was 96.1%, and two treatments failed. At least one self-reported symptom was declared by 72.5% (n = 29) of patients. Positive impact of HCV cure was observed on various markers of physical and mental health as well as on health habits. CONCLUSION Our program should be considered as a proof of concept, which confirmed the feasibility of a HCV-microelimination program at the scale of an HIV clinical unit. However, 12 months were not sufficient to achieve our objective despite the specific organization.
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Zheng YX, Ma SJ, Xiong YH, Fan XG. Efficacy and safety of direct acting antiviral regimens for hepatitis C virus and human immunodeficiency virus co-infection: systematic review and network meta-analysis. J Gastroenterol Hepatol 2020; 35:1477-1487. [PMID: 32246857 DOI: 10.1111/jgh.15051] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/12/2019] [Revised: 03/07/2020] [Accepted: 03/23/2020] [Indexed: 02/07/2023]
Abstract
BACKGROUND AND AIM Various all-oral direct-acting antiviral (DAA) regimens are being widely used in the treatment of human immunodeficiency virus (HIV)/hepatitis C virus (HCV) co-infected patients; however, the comparative efficacy and safety of different types and combinations of DAAs are not completely clear. There is still a lack of integration of evidence for optimized therapies for HIV/HCV co-infection. METHODS We conducted a systematic literature search in several databases up to January 1, 2020. All the studies that reported the sustained virologic response (SVR) and adverse events of DAAs in HIV/HCV co-infected patients were included. The Bayesian Markov Chain Monte Carlo method was used for the pooled estimates of network meta-analysis. RESULTS We identified 33 eligible articles with 7 combinations of all-oral DAAs for the analyses of efficacy and safety. Grazoprevir-elbasvir ± ribavirin (GZR/EBR ± RBV: 95.6%; 95% CrI, 91.7-98.1%), ombitasvir/paritaprevir/ritonavir and dasabuvir ± ribavirin (3D ± RBV: 95.3%; 95% CrI, 93.4-96.9%), sofosbuvir-ledipasvir ± ribavirin (SOF/LDV ± RBV: 95.2%; 95% CrI, 93.7-96.6%), and sofosbuvir-daclatasvir ± ribavirin (SOF/DCV ± RBV: 94.8%; 95% CrI, 92.5-96.6%) were the most effective combinations for HIV/HCV co-infected patients, with SVR rates of approximately 94% and above while severe adverse events were rare. However, the SVR rates of sofosbuvir-ribavirin (SOF/RBV) and sofosbuvir-simeprevir ± ribavirin (SOF/SMV ± RBV) both failed to reach 90%, and the incidences of adverse events were higher than 5%. CONCLUSIONS Efficacy and safety of all-oral DAAs were in prospect for HIV/HCV co-infection patients. GZR/EBR ± RBV was the optimal combination recommended for HIV/HCV co-infected patients based on the excellent treatment effects and insignificant adverse events.
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Affiliation(s)
- Yi-Xiang Zheng
- Department of Infectious Diseases, Key Laboratory of Viral Hepatitis of Hunan, Xiangya Hospital, Central South University, Changsha, China
| | - Shu-Juan Ma
- Department of Epidemiology and Health Statistics, School of Public Health, Central South University, Changsha, China
| | - Ying-Hui Xiong
- Department of Infectious Diseases, Key Laboratory of Viral Hepatitis of Hunan, Xiangya Hospital, Central South University, Changsha, China
| | - Xue-Gong Fan
- Department of Infectious Diseases, Key Laboratory of Viral Hepatitis of Hunan, Xiangya Hospital, Central South University, Changsha, China
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Machado SM, Vigani AG, Leite AG, Diaz ACM, Ferreira PRA, Carnaúba-Júnior D, Tenore SB, Brandão-Mello CE, Gonzalez MP, Siroma F, Prado KD, Nunes DV, Lisboa-Neto G, Pinho JRR, Malta FM, Azevedo RS, Witkin SS, Mendes-Correa MC. Effectiveness of direct-acting antivirals for hepatitis C virus infection in hepatitis C/HIV coinfected individuals: A multicenter study. Medicine (Baltimore) 2020; 99:e21270. [PMID: 32791706 PMCID: PMC7387014 DOI: 10.1097/md.0000000000021270] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/12/2022] Open
Abstract
In a hepatitis C virus (HCV)/HIV-positive Brazilian cohort, evaluate the safety and efficacy of HCV DAAs, the frequency of resistance substitutions in the HCV NS5A and NS5B genes and identify predictors of treatment failure.Retrospective multicenter study of HCV/HIV patients treated with sofosbuvir (SOF)-based regimens at 10 reference centers in Brazil.Clinical and virological data were collected. Genetic diversity in the NS5A and NS5B genes was assessed by direct nucleotide sequencing. The primary outcome was sustained virological response (SVR) 12 weeks after DAA completion.Of 643 HCV/HIV patients analyzed, 74.7% were male, median CD4+ T cell count was 617 cells/mm, 90% had an undetectable HIV viral load. HCV genotype 1 was detected in 80.2%, and 60% were taking at least 1 medication other than antiretroviral drugs during their DAA therapy. Cirrhosis was present in 42%. An SOF/daclatasvir (DCV) regimen was used in most patients (98%). The frequency of NS5A polymorphisms associated with clinically relevant resistance to DCV was 2%; no relevant NS5B variants were identified. The SVR12 rate was 92.8% in an intention to treat (ITT) analysis and 96% in a modified ITT (m-ITT) analysis. AE occurred in 1.6% of patients. By multivariate analysis, therapeutic failure was associated, in the m-ITT analysis, with concomitant use of anticonvulsant drugs (P = .001), age (P = .04), and female gender (P = .04).SOF/DCV regimens were associated with a high SVR rate in an HCV/HIV population. The use of concurrent anticonvulsant drugs and DAAs decreases the chances of achieving an SVR.
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Affiliation(s)
| | | | | | | | | | | | | | | | | | | | | | | | | | - João Renato R. Pinho
- University of São Paulo School of Medicine, São Paulo
- LIM 07, Institute of Tropical Medicine, São Paulo
| | | | | | - Steven S. Witkin
- Department of Obstetrics and Gynecology, Weill Cornell Medicine, New York, NY
- LIM 52, Institute of Tropical Medicine, São Paulo
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Impact of HIV and chronic kidney disease comorbidities on hepatitis C treatment choices, drug-drug interactions and hepatitis C cure. Int J Clin Pharm 2020; 42:515-526. [PMID: 32100238 PMCID: PMC7192872 DOI: 10.1007/s11096-020-00994-6] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/08/2019] [Accepted: 02/12/2020] [Indexed: 01/03/2023]
Abstract
Background Human immunodeficiency virus (HIV) co-infection and chronic kidney disease add challenges to hepatitis C virus treatment. Objective To conduct a comparative study of treatment choices, drug–drug interactions and clinical outcomes in hepatitis C mono-infected patients, or those with HIV or chronic kidney disease comorbidities. Setting Hepatitis C treatment centers of West Midlands England, United Kingdom. Method An observational study was conducted analyzing datasets of all hepatitis C patients that were referred to a large tertiary liver unit in the West Midlands, UK between July 2015 and January 2018. Patients aged ≥ 18 years with diagnosis of hepatitis C alone or co-infected with HIV or comorbid with chronic kidney disease were eligible. Main outcome measures The treatment choices, relevant potential drug–drug interactions and sustained virologic response 12 weeks post end of treatment were assessed. Results Out of 313 patients, 154 (49.2%) were hepatitis C mono-infected, 124 (39.6%) hepatitis C/HIV co-infected and 35 (11.2%) were hepatitis C/chronic kidney disease comorbid. There were 151 (98.1%) of hepatitis C mono-infected, 110 (88.7%) of hepatitis C/HIV and 20 (57.1%) of hepatitis C/chronic kidney disease patients treated with 1st line regimens. Significantly more patients who had co-morbidity with either HIV or chronic kidney disease were prescribed 2nd line regimens (8.1% and 37.1% respectively), compared to patients with hepatitis C mono-infection (1.9%) (P value < 0.05). Comorbid patients (12.1% of HIV and 25.8% of chronic kidney disease) were more likely to required drug–drug interactions advice (grade 5) than hepatitis C mono-infected (1.8%). Higher cure rates were observed in hepatitis C mono-infected (95.33%), hepatitis C/HIV (96.1%) compared to hepatitis C/chronic kidney disease patients (90.3%). Conclusion This study shows that treatment pathways permitting access to individual treatment adjustments in accordance with comorbidities and with consideration of drug–drug interaction in a multi-disciplinary team, provides successful outcomes in hepatitis C patients co-morbid with HIV or chronic kidney disease.
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Real-world efficacy of direct acting antiviral therapies in patients with HIV/HCV. PLoS One 2020; 15:e0228847. [PMID: 32053682 PMCID: PMC7018045 DOI: 10.1371/journal.pone.0228847] [Citation(s) in RCA: 29] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/21/2019] [Accepted: 01/24/2020] [Indexed: 12/12/2022] Open
Abstract
The advent of direct-acting antiviral (DAA) therapies has dramatically transformed HCV treatment, with most recent trials demonstrating high efficacy rates (>90%) across all genotypes and special populations, including patients with HIV/HCV coinfection. The efficacy rates of HCV treatment are nearly identical between patients with HCV monofection and patients with HIV/HCV coinfection; however, there are limited studies to compare real-world efficacy with efficacy observed in clinical trials. Using a database from HIV clinics across the United States (US), we identified 432 patients with HIV/HCV coinfection who completed DAA therapy from January 1, 2014 to March 31, 2017 and were assessed for efficacy. Efficacy was evaluated as sustained virologic response (SVR) 12 weeks after DAA completion; furthermore, factors associated with achieving SVR12 were identified. In this analysis, we found DAA therapies to be effective, with 94% of the patients achieving SVR12 and 6% experiencing virologic failure. Baseline variables, including older age, HCV viral load <800K IU/ML, FIB-4 score <1.45, absence of depression, diabetes, substance abuse, and use of DAA regimens without ribavirin were significant predictors of achieving SVR12. Patients with fewer comorbidities, better liver health, and lower HCV viral loads at baseline were more likely to achieve treatment success. Our results were consistent with other real-world studies, supporting the use of HCV therapy in HIV/HCV coinfected patients.
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Huhn GD, Ramgopal M, Jain MK, Hinestrosa F, Asmuth DM, Slim J, Goldstein D, Applin S, Ryu JH, Jiang S, Cox S, Das M, Nguyen-Cleary T, Piontkowsky D, Guyer B, Rossaro L, Haubrich RH. HIV/HCV therapy with ledipasvir/sofosbuvir after randomized switch to emtricitabine-tenofovir alafenamide-based single-tablet regimens. PLoS One 2020; 15:e0224875. [PMID: 31995556 PMCID: PMC6988963 DOI: 10.1371/journal.pone.0224875] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/18/2019] [Accepted: 10/08/2019] [Indexed: 12/14/2022] Open
Abstract
INTRODUCTION Guidelines advocate the treatment of HCV in all HIV/HCV co-infected individuals. The aim of this randomized, open-label study (ClinicalTrials.gov identifier: NCT02707601; https://clinicaltrials.gov/ct2/show/NCT02707601) was to evaluate the safety/efficacy of ledipasvir/sofosbuvir (LDV/SOF) co-administered with elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide (E/C/F/TAF) or rilpivirine/F/TAF (R/F/TAF) in HIV-1/HCV co-infected participants. METHODS Participants with HIV-1 RNA <50 copies/mL and chronic HCV-genotype (GT) 1 (HCV treatment-naïve ± compensated cirrhosis or HCV treatment-experienced non-cirrhotic) were randomized 1:1 to switch to E/C/F/TAF or R/F/TAF. If HIV suppression was maintained at Week 8, participants received 12 weeks of LDV/SOF. The primary endpoint was sustained HCV virologic response 12 weeks after LDV/SOF completion (SVR12). RESULTS Of 150 participants, 148 received ≥1 dose of HIV study drug and 144 received LDV/SOF (72 in each F/TAF group; 83% GT1a, 94% HCV treatment-naïve, 12% cirrhotic). Overall, SVR12 was 97% (95% confidence interval: 93-99%). Black race did not affect SVR12. Of four participants not achieving SVR12, one had HCV relapse, one had HCV virologic non-response due to non-adherence, and two missed the post-HCV Week 12 visit. Of 148 participants, 96% receiving E/C/F/TAF and 95% receiving R/F/TAF maintained HIV suppression at Week 24; no HIV resistance was detected. No participant discontinued LDV/SOF or E/C/F/TAF due to adverse events; one participant discontinued R/F/TAF due to worsening of pre-existing hypercholesterolemia. Renal toxicity was not observed in either F/TAF regimen during LDV/SOF co-administration. In conclusion, high rates of HCV SVR12 and maintenance of HIV suppression were achieved with LDV/SOF and F/TAF-based regimens. CONCLUSION This study supports LDV/SOF co-administered with an F/TAF-based regimen in HIV-1/HCV-GT1 co-infected patients.
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Affiliation(s)
- Gregory D. Huhn
- Ruth M Rothstein CORE Center, Chicago, IL, United States of America
| | - Moti Ramgopal
- Midway Research Center, Fort Pierce, FL, United States of America
| | - Mamta K. Jain
- UT Southwestern Medical Center, Dallas, TX, United States of America
| | | | - David M. Asmuth
- University of California Davis, Sacramento, CA, United States of America
| | - Jihad Slim
- Saint Michael's Medical Center, Newark, NJ, United States of America
| | | | - Shauna Applin
- Community Health Care, Tacoma, WA, United States of America
| | - Julie H. Ryu
- Gilead Sciences, Inc., Foster City, CA, United States of America
| | - Shuping Jiang
- Gilead Sciences, Inc., Foster City, CA, United States of America
| | - Stephanie Cox
- Gilead Sciences, Inc., Foster City, CA, United States of America
| | - Moupali Das
- Gilead Sciences, Inc., Foster City, CA, United States of America
| | | | | | - Bill Guyer
- Gilead Sciences, Inc., Foster City, CA, United States of America
| | - Lorenzo Rossaro
- Gilead Sciences, Inc., Foster City, CA, United States of America
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Paik JM, Henry L, Golabi P, Alqahtani SA, Trimble G, Younossi ZM. Presumed Nonalcoholic Fatty Liver Disease Among Medicare Beneficiaries With HIV, 2006-2016. Open Forum Infect Dis 2020; 7:ofz509. [PMID: 31921938 PMCID: PMC6945300 DOI: 10.1093/ofid/ofz509] [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: 08/28/2019] [Accepted: 01/02/2020] [Indexed: 12/11/2022] Open
Abstract
Background Newer treatments for HIV and hepatitis C virus (HCV) have decreased mortality in HIV/HCV patients. Nonalcoholic fatty liver disease (NAFLD) has increased globally; therefore, the prevalence and mortality of NAFLD among HIV (+) patients was assessed. Methods Using Medicare denominator, inpatient, and outpatient files (random 5% sample per year), serial cross-sectional analysis (2006 to 2016) was performed. Joinpoint trend analysis evaluated prevalence and mortality with average annual percent change (AAPC). HIV (+) patients and liver diseases (LDs) were identified using International Classification of Diseases 9/10 codes. NAFLD was presumed using diagnosis codes or codes for metabolic dysfunction and obesity in absence of other LDs. Liver-related HIV (+) indicated HIV (+) patients with LDs. Results Among 28 675 887 Medicare beneficiaries, 47 062 were HIV (+) (mean [SD] age, 51.4 [11.3] years); 11 920 had liver diseases (6923 HCV, 2019 hepatitis B virus [HBV], 2472 presumed NAFLD, 278 alcoholic liver disease [ALD], and 1653 other LDs); 2882 HIV (+) patients died; 1260 had LDs. The prevalence and mortality for non-liver-related HIV (+) decreased (AAPC, –1.1% and –9.1%). Liver-related HIV (+) increased (AAPC, 1.7%; P = .007); mortality leveled off. Prevalence and mortality worsened for presumed NAFLD (AAPC, 9.7% and 10.0%) and improved for HBV and HCV (HBV: AAPC, –3.5% and –8.8%; HCV: AAPC, –0.7% and –4.9%). After adjustments, HCV (odds ratio [OR], 2.00; 95% confidence interval [CI], 1.24–172), HBV (OR, 2.40; 95% CI, 2.09–2.77), ALD (OR, 5.70; 95% CI, 4.34–7.48), and presumed NAFLD (OR, 1.46; 95% CI, 1.24–1.72) increased 1-year mortality. Conclusions Among HIV (+) subjects, viral hepatitis remains the leading LD for increased 1-year mortality, but the prevalence and mortality with presumed NAFLD are increasing.
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Affiliation(s)
- James M Paik
- Betty and Guy Beatty Center for Integrated Research, Inova Health System, Falls Church, VA, USA
| | - Linda Henry
- Center for Outcomes Research in Liver Diseases, Washington, DC, USA
| | - Pegah Golabi
- Betty and Guy Beatty Center for Integrated Research, Inova Health System, Falls Church, VA, USA
| | - Saleh A Alqahtani
- Division of Gastroenterology and Hepatology, Johns Hopkins University, Baltimore, MD, USA
| | - Gregory Trimble
- Center for Liver Disease, Department of Medicine, Inova Fairfax Medical Campus, Falls Church, VA, USA
| | - Zobair M Younossi
- Betty and Guy Beatty Center for Integrated Research, Inova Health System, Falls Church, VA, USA.,Center for Liver Disease, Department of Medicine, Inova Fairfax Medical Campus, Falls Church, VA, USA
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Boerekamps A, Newsum AM, Smit C, Arends JE, Richter C, Reiss P, Rijnders BJA, Brinkman K, van der Valk M, Godfried MH, Goorhuis A, Hovius JW, van der Meer JTM, Kuijpers TW, Nellen FJB, van der Poll DT, Prins JM, van Vugt HJM, Wiersinga WJ, Wit FWMN, van Duinen M, van Eden J, van Hes AMH, Mutschelknauss M, Nobel HE, Pijnappel FJJ, Weijsenfeld AM, Jurriaans S, Back NKT, Zaaijer HL, Berkhout B, Cornelissen MTE, Schinkel CJ, Wolthers KC, van den Berge M, Stegeman A, Baas S, de Looff LH, Wintermans B, Veenemans J, Pronk MJH, Ammerlaan HSM, de Munnik ES, Jansz AR, Tjhie J, Wegdam MCA, Deiman B, Scharnhorst V, van Eeden A, v d V M, Brokking W, Groot M, Elsenburg LJM, Damen M, Kwa IS, van Kasteren MEE, Brouwer AE, van Erve R, de Kruijf-van de Wiel BAFM, Keelan-Pfaf S, van der Ven B, de Kruijf-van de Wiel BAFM, van der Ven B, Buiting AGM, Kabel PJ, Versteeg D, van der Ende ME, Bax HI, van Gorp ECM, Nouwen JL, Schurink CAM, Verbon A, de Vries-Sluijs TEMS, de Jong-Peltenburg NC, Bassant N, van Beek JEA, Vriesde M, van Zonneveld LM, van den Berg-Cameron HJ, de Groot J, de Zeeuw-de Man M, Boucher CAB, Koopmans MPG, van Kampen JJA, Pas SD, Branger J, Rijkeboer-Mes A, Duijf-van de Ven CJHM, Schippers EF, van Nieuwkoop C, van IJperen JM, Geilings J, van der Hut G, van Burgel ND, Haag D, Leyten EMS, Gelinck LBS, van Hartingsveld AY, Meerkerk C, Wildenbeest GS, et alBoerekamps A, Newsum AM, Smit C, Arends JE, Richter C, Reiss P, Rijnders BJA, Brinkman K, van der Valk M, Godfried MH, Goorhuis A, Hovius JW, van der Meer JTM, Kuijpers TW, Nellen FJB, van der Poll DT, Prins JM, van Vugt HJM, Wiersinga WJ, Wit FWMN, van Duinen M, van Eden J, van Hes AMH, Mutschelknauss M, Nobel HE, Pijnappel FJJ, Weijsenfeld AM, Jurriaans S, Back NKT, Zaaijer HL, Berkhout B, Cornelissen MTE, Schinkel CJ, Wolthers KC, van den Berge M, Stegeman A, Baas S, de Looff LH, Wintermans B, Veenemans J, Pronk MJH, Ammerlaan HSM, de Munnik ES, Jansz AR, Tjhie J, Wegdam MCA, Deiman B, Scharnhorst V, van Eeden A, v d V M, Brokking W, Groot M, Elsenburg LJM, Damen M, Kwa IS, van Kasteren MEE, Brouwer AE, van Erve R, de Kruijf-van de Wiel BAFM, Keelan-Pfaf S, van der Ven B, de Kruijf-van de Wiel BAFM, van der Ven B, Buiting AGM, Kabel PJ, Versteeg D, van der Ende ME, Bax HI, van Gorp ECM, Nouwen JL, Schurink CAM, Verbon A, de Vries-Sluijs TEMS, de Jong-Peltenburg NC, Bassant N, van Beek JEA, Vriesde M, van Zonneveld LM, van den Berg-Cameron HJ, de Groot J, de Zeeuw-de Man M, Boucher CAB, Koopmans MPG, van Kampen JJA, Pas SD, Branger J, Rijkeboer-Mes A, Duijf-van de Ven CJHM, Schippers EF, van Nieuwkoop C, van IJperen JM, Geilings J, van der Hut G, van Burgel ND, Haag D, Leyten EMS, Gelinck LBS, van Hartingsveld AY, Meerkerk C, Wildenbeest GS, Heikens E, Groeneveld PHP, Bouwhuis JW, Lammers AJJ, Kraan S, van Hulzen AGW, van der Bliek GL, Bor PCJ, Bloembergen P, Wolfhagen MJHM, Ruijs GJHM, Kroon FP, de Boer MGJ, Scheper H, Jolink H, Vollaard AM, Dorama W, van Holten N, Claas ECJ, Wessels E, den Hollander JG, Pogany K, Roukens A, Kastelijns M, Smit JV, Smit E, Struik-Kalkman D, Tearno C, van Niekerk T, Pontesilli O, Lowe SH, Oude Lashof AML, Posthouwer D, Ackens RP, Burgers K, Schippers J, Weijenberg-Maes B, van Loo IHM, Havenith TRA, Mulder JW, Vrouenraets SME, Lauw FN, van Broekhuizen MC, Vlasblom DJ, Smits PHM, Weijer S, El Moussaoui R, Bosma AS, van Vonderen MGA, van Houte DPF, Kampschreur LM, Dijkstra K, Faber S, Weel J, Kootstra GJ, Delsing CE, van der Burg-van de Plas M, Heins H, Lucas E, Kortmann W, van Twillert G, Renckens R, Ruiter-Pronk D, van Truijen-Oud FA, Cohen Stuart JWT, IJzerman EP, Jansen R, Rozemeijer W, van der Reijden WA, van den Berk GEL, Blok WL, Frissen PHJ, Lettinga KD, Schouten WEM, Veenstra J, Brouwer CJ, Geerders GF, Hoeksema K, Kleene MJ, van der Meché IB, Spelbrink M, Toonen AJM, Wijnands S, Kwa D, Regez R, van Crevel R, Keuter M, van der Ven AJAM, ter Hofstede HJM, Dofferhoff ASM, Hoogerwerf J, Grintjes-Huisman KJT, de Haan M, Marneef M, Hairwassers A, Rahamat-Langendoen J, Stelma FF, Burger D, Gisolf EH, Hassing RJ, Claassen M, ter Beest G, van Bentum PHM, Langebeek N, Tiemessen R, Swanink CMA, van Lelyveld SFL, Soetekouw R, van der Prijt LMM, van der Swaluw J, Bermon N, van der Reijden WA, Jansen R, Herpers BL, Veenendaal D, Verhagen DWM, van Wijk M, Bierman WFW, Bakker M, Kleinnijenhuis J, Kloeze E, Stienstra Y, Wilting KR, Wouthuyzen-Bakker M, Boonstra A, van der Meulen PA, de Weerd DA, Niesters HGM, van Leer-Buter CC, Knoester M, Hoepelman AIM, Barth RE, Bruns AHW, Ellerbroek PM, Mudrikova T, Oosterheert JJ, Schadd EM, Wassenberg MWM, van Zoelen MAD, Aarsman K, van Elst-Laurijssen DHM, de Kroon I, van Rooijen CSAM, van Berkel M, van Rooijen CSAM, Schuurman R, Verduyn-Lunel F, Wensing AMJ, Peters EJG, van Agtmael MA, Bomers M, Heitmuller M, Laan LM, Ang CW, van Houdt R, Pettersson AM, Vandenbroucke-Grauls CMJE, Reiss P, Bezemer DO, van Sighem AI, Smit C, Wit FWMN, Boender TS, Zaheri S, Hillebregt M, de Jong A, Bergsma D, Grivell S, Jansen A, Raethke M, Meijering R, Rutkens T, de Groot L, van den Akker M, Bakker Y, Bezemer M, Claessen E, El Berkaoui A, Geerlinks J, Koops J, Kruijne E, Lodewijk C, van der Meer R, Munjishvili L, Paling F, Peeck B, Ree C, Regtop R, Ruijs Y, Schoorl M, Timmerman A, Tuijn E, Veenenberg L, van der Vliet S, Wisse A, de Witte EC, Woudstra T, Tuk B. High Treatment Uptake in Human Immunodeficiency Virus/Hepatitis C Virus-Coinfected Patients After Unrestricted Access to Direct-Acting Antivirals in the Netherlands. Clin Infect Dis 2019; 66:1352-1359. [PMID: 29186365 DOI: 10.1093/cid/cix1004] [Show More Authors] [Citation(s) in RCA: 55] [Impact Index Per Article: 9.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/14/2017] [Accepted: 11/20/2017] [Indexed: 12/24/2022] Open
Abstract
Background The Netherlands has provided unrestricted access to direct-acting antivirals (DAAs) since November 2015. We analyzed the nationwide hepatitis C virus (HCV) treatment uptake among patients coinfected with human immunodeficiency virus (HIV) and HCV. Methods Data were obtained from the ATHENA HIV observational cohort in which >98% of HIV-infected patients ever registered since 1998 are included. Patients were included if they ever had 1 positive HCV RNA result, did not have spontaneous clearance, and were known to still be in care. Treatment uptake and outcome were assessed. When patients were treated more than once, data were included from only the most recent treatment episode. Data were updated until February 2017. In addition, each treatment center was queried in April 2017 for a data update on DAA treatment and achieved sustained virological response. Results Of 23574 HIV-infected patients ever linked to care, 1471 HCV-coinfected patients (69% men who have sex with men, 15% persons who [formerly] injected drugs, and 15% with another HIV transmission route) fulfilled the inclusion criteria. Of these, 87% (1284 of 1471) had ever initiated HCV treatment between 2000 and 2017, 76% (1124 of 1471) had their HCV infection cured; DAA treatment results were pending in 6% (92 of 1471). Among men who have sex with men, 83% (844 of 1022) had their HCV infection cured, and DAA treatment results were pending in 6% (66 of 1022). Overall, 187 patients had never initiated treatment, DAAs had failed in 14, and a pegylated interferon-alfa-based regimen had failed in 54. Conclusions Fifteen months after unrestricted DAA availability the majority of HIV/HCV-coinfected patients in the Netherlands have their HCV infection cured (76%) or are awaiting DAA treatment results (6%). This rapid treatment scale-up may contribute to future HCV elimination among these patients.
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Affiliation(s)
- Anne Boerekamps
- Department of Internal Medicine and Infectious Diseases, Erasmus Medical Center, Rotterdam
| | - Astrid M Newsum
- Department of Infectious Diseases Research and Prevention, Public Health Service of Amsterdam.,Division of Infectious Diseases, Amsterdam Infection and Immunity Institute, Academic Medical Center
| | | | - Joop E Arends
- Department of Internal Medicine, Section Infectious Diseases, University Medical Center Utrecht
| | - Clemens Richter
- Department of Internal Medicine and Infectious Diseases, Rijnstate Hospital, Arnhem
| | - Peter Reiss
- Division of Infectious Diseases, Amsterdam Infection and Immunity Institute, Academic Medical Center.,Stichting HIV Monitoring, Amsterdam.,Department of Global Health, Academic Medical Center and Amsterdam Institute for Global Health and Development
| | - Bart J A Rijnders
- Department of Internal Medicine and Infectious Diseases, Erasmus Medical Center, Rotterdam
| | - Kees Brinkman
- Department of Internal Medicine and Infectious Diseases, Onze Lieve Vrouwe Gasthuis, Amsterdam, the Netherlands
| | - Marc van der Valk
- Division of Infectious Diseases, Amsterdam Infection and Immunity Institute, Academic Medical Center
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Integrated Care for the Use of Direct-acting Antivirals in Patients With Chronic Hepatitis C and Substance Use Disorder. J Addict Med 2019; 12:346-352. [PMID: 29702515 DOI: 10.1097/adm.0000000000000415] [Citation(s) in RCA: 15] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/22/2022]
Abstract
OBJECTIVES Since little is currently known about predictors of response to direct-acting antiviral agents (DAAs) in people who inject drugs, we undertook an analysis of patients attending a hepatitis clinic with addiction services (outpatient clinics and inpatient services) to examine the outcomes associated with the treatment of difficult-to-manage patients with substance use. Our experience was based on integrated care. METHOD A retrospective analysis was undertaken of 50 patients with hepatitis C virus (HCV) and a history of addiction who received treatment with DAAs, according to European guidelines. These regimens were sofosbuvir/ledipasvir for 8 weeks (n = 3), sofosbuvir/ledipasvir ± ribavirin for 12 weeks (n = 19), sofosbuvir/daclatasvir for 12 weeks (n = 20), sofosbuvir/simeprevir (n = 1), or sofosbuvir/daclatasvir for 24 weeks (n = 7). Characteristics of patients who did versus did not achieve a sustained virologic response (SVR) 12 weeks after treatment were compared by univariate analysis. RESULTS Forty-two patients (84%) were male; mean age was 46.2 ± 7.3 years. Genotypes were 1 (n = 21), 2 (n = 4), 3 (n = 18), 4 (n = 6), or 6 (n = 1). Most patients were treatment-naïve (n = 38). Five patients had coinfection with human immunodeficiency virus (n = 4) or hepatitis B (n = 1), 28 (56%) had evidence of cirrhosis on FibroScan (>12.5 kPa), and 34 (68%) were receiving opioid substitution therapy. Psychiatric disease, illicit drug use, unemployment, and homelessness/precarious housing were common. Forty-five patients (90%) achieved SVR, 2 were lost to follow-up, and 3 had treatment relapse. CONCLUSIONS SVR was not significantly associated with sociodemographic or virological characteristics, treatment, social environment, alcohol/drug use, and adherence. Although adherence was slightly worse than in "usual" patients, it did not affect the SVR rate. In these difficult-to-manage patients with HCV and substance use disorder, the real-world SVR rate (90%) was similar to that in nonaddicted populations.
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Breskin A, Westreich D, Hurt CB, Cole SR, Hudgens MG, Seaberg EC, Thio CL, Tien PC, Adimora AA. The Effects of Hepatitis C Treatment Eligibility Criteria on All-cause Mortality Among People With Human Immunodeficiency Virus. Clin Infect Dis 2019; 69:1613-1620. [PMID: 30615096 PMCID: PMC6792128 DOI: 10.1093/cid/ciz008] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/15/2018] [Accepted: 01/04/2019] [Indexed: 01/26/2023] Open
Abstract
BACKGROUND The cost of direct-acting antivirals (DAAs) for hepatitis C virus (HCV) prompted many payers to restrict treatment to patients who met non-evidence-based criteria. These restrictions have implications for survival of people with HCV, especially for people with human immunodeficiency virus (HIV)/HCV coinfection who are at high risk for liver disease progression. The goal of this work was to estimate the effects of DAA access policies on 10-year all-cause mortality among people with HIV. METHODS The study population included 3056 adults with HIV in the Women's Interagency HIV Study and Multicenter AIDS Cohort Study from 1 October 1994 through 30 September 2015. We used the parametric g-formula to estimate 10-year all-cause mortality under DAA access policies that included treating (i) all people with HCV; (ii) only people with suppressed HIV; (iii) only people with severe fibrosis; and (iv) only people with HIV suppression and severe fibrosis. RESULTS The 10-year risk difference of treating all coinfected persons with DAAs compared with no treatment was -3.7% (95% confidence interval [CI], -9.1% to .6%). Treating only those with suppressed HIV and severe fibrosis yielded a risk difference of -1.1% (95% CI, -2.8% to .6%), with 51% (95% CI, 38%-59%) of coinfected persons receiving DAAs. Treating a random selection of 51% of coinfected persons at baseline decreased the risk by 1.9% (95% CI, -4.7% to .3%). CONCLUSIONS Restrictive DAA access policies may decrease survival compared to treating similar proportions of people with HIV/HCV coinfection with DAAs at random. These findings suggest that lives could be saved by thoughtfully revising access policies.
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Affiliation(s)
- Alexander Breskin
- Department of EpidemiologyInstitute for Global Health and Infectious Diseases, Baltimore, Maryland
| | - Daniel Westreich
- Department of EpidemiologyInstitute for Global Health and Infectious Diseases, Baltimore, Maryland
| | - Christopher B Hurt
- Institute for Global Health and Infectious Diseases, Baltimore, Maryland
| | - Stephen R Cole
- Department of EpidemiologyInstitute for Global Health and Infectious Diseases, Baltimore, Maryland
| | - Michael G Hudgens
- Department of Biostatistics, University of North Carolina at Chapel Hill, Baltimore, Maryland
| | - Eric C Seaberg
- Department Epidemiology, Johns Hopkins University, Baltimore, Maryland
| | - Chloe L Thio
- Department Medicine, Johns Hopkins University, Baltimore, Maryland
| | - Phyllis C Tien
- Department of Medicine, University of California, San Francisco
| | - Adaora A Adimora
- Department of EpidemiologyInstitute for Global Health and Infectious Diseases, Baltimore, Maryland
- Institute for Global Health and Infectious Diseases, Baltimore, Maryland
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Falade-Nwulia O, Sutcliffe CG, Mehta SH, Moon J, Chander G, Keruly J, Katzianer J, Thomas DL, Moore RD, Sulkowski MS. Hepatitis C Elimination in People With HIV Is Contingent on Closing Gaps in the HIV Continuum. Open Forum Infect Dis 2019; 6:ofz426. [PMID: 31667200 PMCID: PMC6814283 DOI: 10.1093/ofid/ofz426] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/07/2019] [Accepted: 09/25/2019] [Indexed: 12/15/2022] Open
Abstract
BACKGROUND Bolstered by the high efficacy of hepatitis C virus (HCV) treatment, the World Health Organization has called for HCV elimination by 2030. People with HIV (PWH) have been identified as a population in which elimination should be prioritized. METHODS We examined progress in HCV elimination through the HCV care continuum among patients infected with HIV/HCV receiving HIV care at Johns Hopkins Hospital in Baltimore, Maryland, United States. Patients with HIV care visits in at least 2 consecutive years were followed through December 15, 2018, for referral to HCV care, treatment initiation, and cure. RESULTS Among 593 HIV/HCV-coinfected individuals, 547 (92%) were referred for HCV care, 517 (87%) were evaluated for HCV treatment, 457 (77%) were prescribed HCV treatment, 426 (72%) initiated treatment, and 370 (62%) achieved HCV cure. In multivariable analysis, advanced liver disease (hazard ratio [HR], 1.48; 95% confidence interval [CI], 1.17-1.88) remained significantly positively associated with HCV treatment initiation. Conversely, being insured by state Medicaid (HR, 0.75; 95% CI, 0.61-0.92), having an HIV RNA >400 copies/mL (HR, 0.29; 95% CI, 0.18-0.49), and having missed 1%-24% (HR, 0.72; 95% CI, 0.54-0.97), 25%-49% (HR, 0.66; 95% CI, 0.49-0.89), and ≥50% of HIV care visits (HR, 0.39; 95% CI, 0.25-0.60) were significantly negatively associated with HCV treatment initiation. CONCLUSIONS HCV infection can be eliminated in PWH. However, HCV elimination requires unrestricted access to HCV treatment and improved methods of retaining people in medical care.
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Affiliation(s)
- Oluwaseun Falade-Nwulia
- Division of Infectious Disease, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
| | - Catherine G Sutcliffe
- Johns Hopkins Bloomberg School of Public Health, Johns Hopkins University, Baltimore, Maryland, USA
| | - Shruti H Mehta
- Johns Hopkins Bloomberg School of Public Health, Johns Hopkins University, Baltimore, Maryland, USA
| | - Juhi Moon
- Division of Infectious Disease, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
| | - Geetanjali Chander
- Division of General Internal Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
| | - Jeanne Keruly
- Division of Infectious Disease, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
| | - Jennifer Katzianer
- Johns Hopkins Pharmaquip, Johns Hopkins Medical Institutions, Baltimore, Maryland, USA
| | - David L Thomas
- Division of Infectious Disease, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
| | - Richard D Moore
- Division of General Internal Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
| | - Mark S Sulkowski
- Division of Infectious Disease, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
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Wilson E, Covert E, Hoffmann J, Comstock E, Emmanuel B, Tang L, Husson J, Chua J, Price A, Mathur P, Rosenthal E, Kattakuzhy S, Masur H, Kottilil S. A pilot study of safety and efficacy of HCV retreatment with sofosbuvir/velpatasvir/voxilaprevir in patients with or without HIV (RESOLVE STUDY). J Hepatol 2019; 71:498-504. [PMID: 31173815 PMCID: PMC10885189 DOI: 10.1016/j.jhep.2019.05.021] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/28/2019] [Revised: 04/30/2019] [Accepted: 05/23/2019] [Indexed: 12/17/2022]
Abstract
BACKGROUND & AIMS Cure rates in response to retreatment with sofosbuvir/velpatasvir/voxilaprevir (SOF/VEL/VOX) are high, but this regimen has not been studied in patients with a history of poor adherence or treatment interruption, nor in patients with HIV/HCV coinfection. Herein, we aimed to assess the safety and efficacy of this combination in patients with genotype 1 HCV infection who had relapsed following combination direct-acting antiviral (DAA) therapy, regardless of HIV infection or previous treatment course. METHODS The RESOLVE study was a multicenter, open-label, phase IIb study investigating the safety, tolerability and efficacy of SOF/VEL/VOX in 77 patients with virologic rebound following combination DAA therapy. Efficacy was defined as HCV RNA below the lower limit of detection 12 weeks after the end of treatment (SVR12), while safety endpoints included the incidence of grade 3 and 4 adverse events (AEs) following treatment, and the proportion of patients who stopped treatment prematurely due to AEs. RESULTS In an intent-to-treat analysis, 70/77 (90.9%, 95% CI 82.1-95.8%) patients achieved SVR12, including 14/17 (82.4%) HIV coinfected participants and 18/22 (81.8%) of those with previous non-completion of DAA therapy. In an analysis of all patients who completed 12 weeks of study medication, 70/71 patients (99%) achieved SVR12. One patient experienced a grade 3 AE, and 4 experienced a grade 4 AE, all unrelated to study participation. Reported AEs were similar in HIV-coinfected patients, and patients receiving dolutegravir-based antiretroviral treatment experienced no clinically significant increases in aminotransferases. CONCLUSION Retreatment with 12 weeks of SOF/VEL/VOX was safe and effective in patients with relapsed HCV following initial combination DAA-based treatment. Treatment response was not affected by HIV coinfection or previous treatment course. LAY SUMMARY Twelve weeks of the combination of direct-acting antivirals (SOF/VEL/VOX) was safe and effective in patients with relapsed hepatitis C virus infection who had previously received combination therapy with direct-acting antivirals. Treatment response was not diminished by HIV coinfection, or non-completion of previous direct-acting antiviral-based therapy.
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Affiliation(s)
- Eleanor Wilson
- Division of Clinical Care and Research, Institute of Human Virology, University of Maryland School of Medicine, Baltimore, MD 21201, USA.
| | - Emily Covert
- Division of Clinical Care and Research, Institute of Human Virology, University of Maryland School of Medicine, Baltimore, MD 21201, USA; Critical Care Medicine Department, Clinical Center, National Institutes of Health, Bethesda, MD 20892, USA
| | - Jennifer Hoffmann
- Division of Clinical Care and Research, Institute of Human Virology, University of Maryland School of Medicine, Baltimore, MD 21201, USA
| | - Emily Comstock
- Division of Clinical Care and Research, Institute of Human Virology, University of Maryland School of Medicine, Baltimore, MD 21201, USA
| | - Benjamin Emmanuel
- Division of Clinical Care and Research, Institute of Human Virology, University of Maryland School of Medicine, Baltimore, MD 21201, USA
| | - Lydia Tang
- Division of Clinical Care and Research, Institute of Human Virology, University of Maryland School of Medicine, Baltimore, MD 21201, USA
| | - Jennifer Husson
- Division of Clinical Care and Research, Institute of Human Virology, University of Maryland School of Medicine, Baltimore, MD 21201, USA
| | - Joel Chua
- Division of Clinical Care and Research, Institute of Human Virology, University of Maryland School of Medicine, Baltimore, MD 21201, USA
| | - Angie Price
- Division of Clinical Care and Research, Institute of Human Virology, University of Maryland School of Medicine, Baltimore, MD 21201, USA
| | - Poonam Mathur
- Division of Clinical Care and Research, Institute of Human Virology, University of Maryland School of Medicine, Baltimore, MD 21201, USA
| | - Elana Rosenthal
- Division of Clinical Care and Research, Institute of Human Virology, University of Maryland School of Medicine, Baltimore, MD 21201, USA
| | - Sarah Kattakuzhy
- Division of Clinical Care and Research, Institute of Human Virology, University of Maryland School of Medicine, Baltimore, MD 21201, USA
| | - Henry Masur
- Critical Care Medicine Department, Clinical Center, National Institutes of Health, Bethesda, MD 20892, USA
| | - Shyam Kottilil
- Division of Clinical Care and Research, Institute of Human Virology, University of Maryland School of Medicine, Baltimore, MD 21201, USA
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Xiao H, Chen J, Wang J, Li J, Yang F, Lu H. Antiviral therapy for HCV in hemophilia A patients with HIV-1 co-infection. Medicine (Baltimore) 2019; 98:e16524. [PMID: 31348267 PMCID: PMC6708971 DOI: 10.1097/md.0000000000016524] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/12/2018] [Revised: 06/04/2019] [Accepted: 06/26/2019] [Indexed: 11/25/2022] Open
Abstract
Anti-hepatitis C virus (HCV) treatment for human immunodeficiency virus (HIV)/HCV co-positive patients with hemophilia A presents numerous problems in terms of safety and effectiveness. The emergence of direct-acting antiviral (DAA) regimens has led to tremendous changes in the management of HIV/HCV co-infection over the past few years, but the application of DAA in patients with hemophilia complicated with HIV/HCV co-infection has rarely been reported.We retrospectively analyzed the clinical course and outcome of hemophilia A patients with HIV/HCV co-infection receiving DAA with a focus on the virological response, changes in cluster of differentiation 4 lymphocyte (CD4) count, side effects, and impact on bleeding before and after DAA therapy.A total of 12 hemophilia A patients with HIV/HCV co-infection were included, 9 of which were severe. All the patients were in stable states with CD4 counts >200/mm and plasma HIV ribonucleic acid (RNA) suppressed (<40 IU/mL) while taking the antiretroviral regimen. Majority of the patients (n = 9, 75.0%) were infected with HCV genotype (GT) 1b, while 2 and 1 was infected with HCV GT 2i and HCV GT 3, respectively.After 12 weeks of DAA treatment, 11 patients (91.7%) obtained sustained virologic response within 24 weeks of discontinuation of treatment (SVR24), except 1 patient who was treated with sofosbuvir (SOF) + pegylated interferon + ribavirin (PR), which was then switched to daclatasvir (DCV) + asunaprevir (ASV) for 12 weeks; this patient then achieved SVR24. During DAA treatment, HIV RNA in all the patients was constantly suppressed, while CD4 counts showed no obvious change.The most common treatment-emergent adverse events were weakness and loss of appetite (generally mild). There was no evidence of an increased tendency of bleeding, and changes in response to replacement.DAA therapy offered a safe and well-tolerated management strategy for HIV/HCV co-infected patients with hemophilia A. An awareness of the potential drug-drug interactions (DDI) between DAA and combination antiretroviral therapy (cART) by clinicians is important for optimal management of co-infected patients.
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El-Garem H, AbdAllah M, Omar H, Cordie A, Abdel Alem S, Mohey Eldin Elzahry MA, Ghaith D, Abou El-Soud NH, Kamal W, Elsharkawy A, Esmat G. DAAs therapy associated with improved hepatic fibrosis in HCV-GT4 patients co-infected with HIV. Expert Rev Gastroenterol Hepatol 2019; 13:693-698. [PMID: 31043104 DOI: 10.1080/17474124.2019.1614441] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/13/2019] [Accepted: 04/26/2019] [Indexed: 12/13/2022]
Abstract
Background: The present work aimed at evaluation of the potential dynamic changes in hepatic fibrosis following treatment of chronic HCV using DAAs in patients coinfected with HIV. Patients and methods: In total, 50 HCV/HIV coinfected patients [age; 34.68 ± 10.38 years, 82% men] were included. For all included patients, liver stiffness measured using transient elastography as well as serum liver fibrosis scores; [fibrosis-4 (FIB-4) score and the aspartate aminotransferase to platelet ratio index (APRI)] were calculated at baseline and at 12 and 24-weeks following 12 weeks therapy of HCV with once daily sofosbuvir 400 mg plus daclatasvir 60 mg. Results: Most of the included patients (70%, n = 35) were on anti-retroviral therapy. SVR24 was achieved by 93.48% of the patients. There was significant serial improvement in baseline liver stiffness measurement (LSM), FIB-4 and APRI among responders; [LSM: baseline, 7.05 ± 4.84 kPa vs. 5.66 ± 2.63 kPa at SVR24, p < 0.001], [FIB-4: baseline, 1.24 ± 1.08 vs. 0.93 ± 0.64 at SVR24, p 0.001) and (APRI: baseline, 0.725 ± 0.66 vs. 0.36 ± 0.19at SVR24, p 0.001) respectively. Conclusion: Treatment of HCV patients coinfected with HIV using DAAs is associated with a rapid significant regression in hepatic fibrosis, as evaluated by FibroScan, FIB-4, and APRI scores.
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Affiliation(s)
- Hassan El-Garem
- a Endemic Medicine and Hepatology Department, Faculty of Medicine , Cairo University , Giza , Egypt
| | - Mohamed AbdAllah
- b Medical Research Division , National Research Center , Giza , Egypt
| | - Heba Omar
- a Endemic Medicine and Hepatology Department, Faculty of Medicine , Cairo University , Giza , Egypt
| | - Ahmed Cordie
- a Endemic Medicine and Hepatology Department, Faculty of Medicine , Cairo University , Giza , Egypt
| | - Shereen Abdel Alem
- a Endemic Medicine and Hepatology Department, Faculty of Medicine , Cairo University , Giza , Egypt
| | | | - Doaa Ghaith
- c Clinical and Chemical Pathology Department, Faculty of Medicine , Cairo University , Giza , Egypt
| | | | - Walid Kamal
- d Preventive sector , Ministry of Health , Cairo , Egypt
| | - Aisha Elsharkawy
- a Endemic Medicine and Hepatology Department, Faculty of Medicine , Cairo University , Giza , Egypt
| | - Gamal Esmat
- a Endemic Medicine and Hepatology Department, Faculty of Medicine , Cairo University , Giza , Egypt
- e Badr University , Cairo , Egypt
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Breskin A, Westreich D, Cole SR, Hudgens MG, Hurt CB, Seaberg EC, Thio CL, Tien PC, Adimora AA. The Effects of Hepatitis C Infection and Treatment on All-cause Mortality Among People Living With Human Immunodeficiency Virus. Clin Infect Dis 2019; 68:1152-1159. [PMID: 30321289 PMCID: PMC6424073 DOI: 10.1093/cid/ciy588] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/19/2018] [Accepted: 07/23/2018] [Indexed: 12/13/2022] Open
Abstract
BACKGROUND Persons living with human immunodeficiency virus (HIV; PLwH) are commonly co-infected with hepatitis C virus (HCV). Most co-infected individuals can achieve a sustained HCV virologic response after treatment with direct-acting antivirals (DAA). However, the effect of HCV co-infection and DAA treatment on mortality after initiating antiretroviral therapy (ART) is unknown for PLwH. METHODS We analyzed data from the Women's Interagency HIV Study and the Multicenter AIDS Cohort Study. Participants included those who had prevalent HIV or seroconverted during follow-up; all were antiretroviral-naive and acquired immunodeficiency syndrome (AIDS)-free prior to their first visit after 1 October 1994. The follow-up lasted 10 years or until 30 September 2015. We used parametric g-computation to estimate the effects of HCV infection and DAA treatment on mortality had participants initiated ART at study entry. RESULTS Of the 3056 eligible participants, 58% were female and 18% had HCV. The estimated 10-year all-cause mortality risk in the scenario in which no PLwH had HCV was 10.4% (95% confidence interval [CI] 6.0-18.0%). The 10-year mortality risk difference for HCV infection was 4.3% (95% CI 0.4-8.9%) and the risk ratio was 1.4 (95% CI 1.0-1.9). The risk difference for DAA treatment was -3.8% (95% CI -9.2-0.9%) and the risk ratio was 0.8 (95% CI 0.6-1.1). CONCLUSIONS HCV co-infection remains an important risk factor for mortality among PLwH after initiating ART according to modern guidelines, and DAAs are effective at reducing mortality in this population. HCV prevention and treatment interventions should be prioritized to reduce mortality among PLwH.
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Affiliation(s)
- Alexander Breskin
- Department of Epidemiology, University of North Carolina at Chapel Hill
| | - Daniel Westreich
- Department of Epidemiology, University of North Carolina at Chapel Hill
| | - Stephen R Cole
- Department of Epidemiology, University of North Carolina at Chapel Hill
| | - Michael G Hudgens
- Department of Biostatistics, University of North Carolina at Chapel Hill
| | - Christopher B Hurt
- Institute for Global Health and Infectious Diseases, University of North Carolina at Chapel Hill
| | - Eric C Seaberg
- Department of Epidemiology, Johns Hopkins University, Baltimore, Maryland
| | - Chloe L Thio
- Department of Medicine, Johns Hopkins University, Baltimore, Maryland
| | - Phyllis C Tien
- Department of Medicine, University of California, San Francisco
| | - Adaora A Adimora
- Department of Epidemiology, University of North Carolina at Chapel Hill
- Institute for Global Health and Infectious Diseases, University of North Carolina at Chapel Hill
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Gayam V, Hossain MR, Khalid M, Chakaraborty S, Mukhtar O, Dahal S, Mandal AK, Gill A, Garlapati P, Ramakrishnaiah S, Mowyad K, Sherigar J, Mansour M, Mohanty S. Real-World Clinical Efficacy and Tolerability of Direct-Acting Antivirals in Hepatitis C Monoinfection Compared to Hepatitis C/Human Immunodeficiency Virus Coinfection in a Community Care Setting. Gut Liver 2019; 12:694-703. [PMID: 29938459 PMCID: PMC6254621 DOI: 10.5009/gnl18004] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/29/2017] [Revised: 02/27/2018] [Accepted: 03/26/2018] [Indexed: 12/12/2022] Open
Abstract
Background/Aims Limited data exist comparing the safety and efficacy of direct-acting antivirals (DAAs) in hepatitis C virus (HCV) monoinfected and HCV/human immunodeficiency virus (HIV) coinfected patients in the real-world clinic practice setting. Methods All HCV monoinfected and HCV/HIV coinfected patients treated with DAAs between January 2014 and October 2017 in community clinic settings were retrospectively analyzed. Pretreatment baseline patient characteristics, treatment efficacy, factors affecting sustained virologic response at 12 weeks (SVR12) after treatment, and adverse reactions were compared between the groups. Results A total of 327 patients were included in the study, of which 253 were HCV monoinfected, and 74 were HCV/HIV coinfected. There was a statistically significant difference observed in SVR12 when comparing HCV monoinfection and HCV/HIV coinfection (94% and 84%, respectively, p=0.005). However, there were no significant factors identified as a predictor of a reduced response. The most common adverse effect was fatigue (27%). No significant drug interaction was observed between DAA and antiretroviral therapy. None of the patients discontinued the treatment due to adverse events. Conclusions In a real-world setting, DAA regimens have lower SVR12 in HCV/HIV coinfection than in HCV monoinfection. Further studies involving a higher number of HCV/HIV coinfected patients are needed to identify real predictors of a reduced response.
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Affiliation(s)
- Vijay Gayam
- Department of Medicine and Gastroenterology, Interfaith Medical Center, New York, NY, USA
| | - Muhammad Rajib Hossain
- Department of Medicine and Gastroenterology, Interfaith Medical Center, New York, NY, USA
| | - Mazin Khalid
- Department of Medicine and Gastroenterology, Interfaith Medical Center, New York, NY, USA
| | - Sandipan Chakaraborty
- Department of Medicine and Gastroenterology, Interfaith Medical Center, New York, NY, USA
| | - Osama Mukhtar
- Department of Medicine and Gastroenterology, Interfaith Medical Center, New York, NY, USA
| | - Sumit Dahal
- Department of Medicine and Gastroenterology, Interfaith Medical Center, New York, NY, USA
| | - Amrendra Kumar Mandal
- Department of Medicine and Gastroenterology, Interfaith Medical Center, New York, NY, USA
| | - Arshpal Gill
- Department of Medicine and Gastroenterology, Interfaith Medical Center, New York, NY, USA
| | - Pavani Garlapati
- Department of Medicine and Gastroenterology, Interfaith Medical Center, New York, NY, USA
| | | | - Khalid Mowyad
- Department of Medicine, Detroit Medical Center, Wayne State University, Detroit, MI, USA
| | - Jagannath Sherigar
- Division of Gastroenterology and Hepatology, Department of Medicine, New York-Presbyterian Brooklyn Methodist Hospital, New York, NY, USA
| | - Mohammed Mansour
- Department of Medicine and Gastroenterology, Interfaith Medical Center, New York, NY, USA
| | - Smruti Mohanty
- Division of Gastroenterology and Hepatology, Department of Medicine, New York-Presbyterian Brooklyn Methodist Hospital, New York, NY, USA
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van Santen DK, van der Helm JJ, Touloumi G, Pantazis N, Muga R, Gunsenheimer-Bartmeyer B, Gill MJ, Sanders E, Kelleher A, Zangerle R, Porter K, Prins M, Geskus RB. Effect of incident hepatitis C infection on CD4+ cell count and HIV RNA trajectories based on a multinational HIV seroconversion cohort. AIDS 2019; 33:327-337. [PMID: 30325767 DOI: 10.1097/qad.0000000000002040] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Abstract
BACKGROUND Most studies on hepatitis C virus (HCV)/HIV-coinfection do not account for the order and duration of these two infections. We aimed to assess the effect of incident HCV infection, and its timing relative to HIV seroconversion (HIVsc) in HIV-positive MSM on their subsequent CD4+ T-cell count and HIV RNA viral load trajectories. METHODS We included MSM with well estimated dates of HIVsc from 17 cohorts within the CASCADE Collaboration. HCV-coinfected MSM were matched to as many HIV monoinfected MSM as possible by HIV-infection duration and combination antiretroviral therapy (cART) use. We used multilevel random-effects models stratified by cART use to assess differences in CD4+ cell count and HIV RNA viral load trajectories by HCV-coinfection status. FINDINGS We matched 214 (ART-naive) and 147 (on cART) HCV-coinfected MSM to 5384 and 3954, respectively, matched controls. The timing of HCV seroconversion (HCVsc) relative to HIVsc had no demonstrable effect on HIV RNA viral load or CD4+ cell count trajectories. In the first 2-3 years following HCVsc CD4 cell counts were lower among HCV-coinfected MSM, but became comparable with HIV monoinfected MSM thereafter. In ART-naive MSM, during the first 2 years after HCVsc, HIV RNA viral load levels were lower or comparable with HIV monoinfected, tending to be higher thereafter. In MSM on cART, HCV had no significant effect on having a detectable HIV RNA viral load. INTERPRETATION Irrespective of the duration of HIV infection when HCV is acquired, CD4+ cell counts were temporarily lower following HCVsc, even when on cART. The clinical implications of our findings remain to be further elucidated.
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Domínguez-Domínguez L, Bisbal O, Matarranz M, Lagarde M, Pinar Ó, Hernando A, Lumbreras C, Rubio R, Pulido F. Predictive factors of hepatitis C virus eradication after interferon-free therapy in HIV coinfection. Eur J Clin Microbiol Infect Dis 2019; 38:725-734. [DOI: 10.1007/s10096-019-03488-0] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/13/2018] [Accepted: 01/13/2019] [Indexed: 12/14/2022]
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Wu J, Huang P, Fan H, Tian T, Xia X, Fu Z, Wang Y, Ye X, Yue M, Zhang Y. Effectiveness of ombitasvir/paritaprevir/ritonavir, dasabuvir for HCV in HIV/HCV coinfected subjects: a comprehensive analysis. Virol J 2019; 16:11. [PMID: 30654809 PMCID: PMC6337763 DOI: 10.1186/s12985-018-1114-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/19/2018] [Accepted: 12/27/2018] [Indexed: 11/17/2022] Open
Abstract
Background Data on the treatment of patients with hepatitis C virus (HCV)/human immunodeficiency virus (HIV) coinfection remains limited. A comprehensive analysis was performed to evaluate the efficacy and safety of ombitasvir (OBV)/paritaprevir (PTV)/ritonavir(r) ± dasabuvir (DSV) ± ribavirin (RBV) for treatment in HCV/HIV coinfected patients. Methods We systematically searched and included studies that enrolled patients with HIV/HCV coinfection using the OBV/PTV/r ± DSV ± RBV regimens and reported sustained virological response after 12 weeks (SVR12) end-of-treatment. Heterogeneity of results was assessed and pooled SVR rates were computed with 95% confidence intervals (95%CI). Subgroup analysis and assessment of publication bias through Egger’s test were further performed. Results Ten studies containing 1358 coinfected patients were included in this study. The pooled estimate of SVR12 was 96.3% (95%CI: 95.1–97.4). Subgroup analysis showed that pooled SVR12 rate was 96.2% (95% CI: 94.8–97.4) for patients with genotype (GT) 1 and 98.8% (95% CI: 95.1–100.0) for those with GT4. The SVR12 rates for the treatment-naïve (TN) and treatment-experienced (TE) patients were 96.8% (95% CI, 94.8–98.5) and 98.9% (95% CI, 96.4–100.0), respectively. Pooled SVR12 rate was 97.8(95%CI: 94.6–99.8) for patients with cirrhosis and 96.7% (95%CI: 95.3–97.8) without cirrhosis. The pooled incidence of any adverse events (AEs) and serious adverse events (SAEs) was 73.9% (95%CI: 38.1–97.6) and 2.7% (95%CI: 0.0–9.5). Publication bias did not exist in this study. Conclusions The comprehensive analysis showed high efficacy for the OBV/PTV/r ± DSV ± RBV regimen in patients coinfected with HIV and HCV, regardless of genotypes, history of treatment and the presence or absence of cirrhosis. Electronic supplementary material The online version of this article (10.1186/s12985-018-1114-4) contains supplementary material, which is available to authorized users.
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Affiliation(s)
- Jingjing Wu
- Department of Epidemiology and Biostatistics, School of Public Health, Nanjing Medical University, Nanjing, 211166, China
| | - Peng Huang
- Department of Epidemiology and Biostatistics, School of Public Health, Nanjing Medical University, Nanjing, 211166, China.,Key Laboratory of Infectious Diseases, School of Public Health, Nanjing Medical University, Nanjing, 211166, China.,Institute of Epidemiology and Microbiology, Huadong Research Institute for Medicine and Biotechnics, Nanjing, 210002, China
| | - Haozhi Fan
- Department of Epidemiology and Biostatistics, School of Public Health, Nanjing Medical University, Nanjing, 211166, China
| | - Ting Tian
- Department of Epidemiology and Biostatistics, School of Public Health, Nanjing Medical University, Nanjing, 211166, China
| | - Xueshan Xia
- Faculty of Life Science and Technology, Kunming University of Science and Technology, Yunnan, 650550, China
| | - Zuqiang Fu
- Department of Epidemiology and Biostatistics, School of Public Health, Nanjing Medical University, Nanjing, 211166, China
| | - Yan Wang
- Department of Epidemiology and Biostatistics, School of Public Health, Nanjing Medical University, Nanjing, 211166, China
| | - Xiangyu Ye
- Department of Epidemiology and Biostatistics, School of Public Health, Nanjing Medical University, Nanjing, 211166, China
| | - Ming Yue
- Department of Infectious Diseases, The First Affiliated Hospital of Nanjing Medical University, Nanjing, 210029, China.
| | - Yun Zhang
- Department of Epidemiology and Biostatistics, School of Public Health, Nanjing Medical University, Nanjing, 211166, China. .,Key Laboratory of Infectious Diseases, School of Public Health, Nanjing Medical University, Nanjing, 211166, China. .,Institute of Epidemiology and Microbiology, Huadong Research Institute for Medicine and Biotechnics, Nanjing, 210002, China.
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Mohazzab-Torabi S, Dolatimehr F, Sharafi H, Safi-Abadi M, Rezaee-Zavareh MS, Bayatpour E, Karimi-Sari H, Alavian SM. Treatment of HCV Infection with Direct-Acting Antiviral Agents in Patients with HIV/HCV Co-Infection: A Systematic Review. HEPATITIS MONTHLY 2018; In Press. [DOI: 10.5812/hepatmon.82971] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/03/2023]
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Sikavi C, Najarian L, Saab S. Similar Sustained Virologic Response in Real-World and Clinical Trial Studies of Hepatitis C/Human Immunodeficiency Virus Coinfection. Dig Dis Sci 2018; 63:2829-2839. [PMID: 30094623 DOI: 10.1007/s10620-018-5215-0] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/24/2018] [Accepted: 07/17/2018] [Indexed: 12/12/2022]
Abstract
BACKGROUND Clinical trials evaluating efficacy of direct-acting antiviral (DAA) therapies demonstrate sustained virologic response (SVR) rates greater than 90% in patients infected with hepatitis C (HCV) and human immunodeficiency virus (HIV). However, generalizability of this data to real-world coinfected populations is unknown. AIM We aim to compare efficacy data from clinical trials to effectiveness data of real-world observational studies that evaluate oral interferon-free HCV treatment regimens in patients infected with HIV and HCV. METHODS We included English-language studies on PubMed and MEDLINE databases from inception until October 2017. Eight clinical trials and 11 observational studies reporting on efficacy data and effectiveness data, respectively, of interferon-free oral DAA regimens in HCV/HIV coinfected patients, were included. RESULTS Of patients in the eight clinical trials evaluated, 93.1% (1218/1308) achieved SVR12; of the 11 real-world observational studies, 90.8% (2269/2499) achieved SVR12. Relative risk between those treated in clinical trials versus observational studies was 0.98. Patients with genotype 1 infection, African-American patients, cirrhotic patients, and patients with prior HCV treatment experience had similar rates of SVR in real-world and clinical trial cohorts. CONCLUSION SVR among real-world HCV/HIV coinfected populations treated with DAA regimens is similar to SVR of patients studied in clinical trials. Historically negative predictors of achieving SVR during the era of interferon-based treatments, such as those with cirrhosis, prior HCV treatment failure, GT1 infection, and African-American race, are not associated with a significantly lower SVR in real-world populations treated with various DAA regimens.
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Affiliation(s)
- Cameron Sikavi
- Departments of Surgery and Medicine, University of California at Los Angeles, Los Angeles, CA, USA
| | - Lisa Najarian
- Departments of Surgery and Medicine, University of California at Los Angeles, Los Angeles, CA, USA
| | - Sammy Saab
- Departments of Surgery and Medicine, University of California at Los Angeles, Los Angeles, CA, USA. .,Pfleger Liver Institute, UCLA Medical Center, 200 Medical Plaza, Suite 214, Los Angeles, CA, 90095, USA.
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Rial-Crestelo D, Rodríguez-Cola M, González-Gasca FJ, Geijo-Martínez P, Belinchón-Moya O, Martínez-Alfaro E, Mateos-Rodríguez F, Barberá JR, Yzusqui M, Casallo S, García M, Espinosa-Gimeno A, Torralba M. Effectiveness of direct-acting antiviral therapy in patients with a HCV/HIV coinfection. A multicenter cohort study. REVISTA ESPANOLA DE ENFERMEDADES DIGESTIVAS 2018; 110:35-43. [PMID: 29271221 DOI: 10.17235/reed.2017.5210/2017] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/20/2022]
Abstract
INTRODUCTION The effectiveness of direct-acting antiviral (DAA) agents has been demonstrated in clinical trials both in patients with mono and coinfections. The goal of the study was to analyze the effectiveness and toxicity of this therapy in real-life patients with a HIV/HCV coinfection and to identify variables that are associated with an unfavorable outcome. METHODS This was a multicenter ambispective study in a cohort of coinfected patients. Data were collected from eight centers in Castilla-La Mancha from 2014 to 2016. An intent-to-treat analysis was performed and any loss to follow-up, treatment withdrawal or toxicity was considered as a failure. RESULTS A total of 229 patients were included with a median age of 49.6 years and the majority were male (83%). Fewer than 10% had a detectable HIV-related viral load (VL). The most prevalent HCV genotype was 1 (65.1%). Fifty percent had cirrhotic liver disease and 65% had over 800,000 copies/ml of HCV VL. The global sustained viral response (SVR) was reached by 91.7% of cases. The most commonly used DAA regimen was sofosbuvir/ledipasvir. Ribavirin was included in 52% of regimens, 65.9% of cases completed 12-week regimens and 30% completed 24-week schemes. There were 19 therapy failures. No differences were observed between the various DAA strategies used. No independent predictor was found for SVR. CONCLUSIONS HCV treatment in coinfected patients is highly successful in terms of SVR rate in the real-life setting and toxicity is exceptional. We identified no specific predictors of an unfavorable outcome.
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Affiliation(s)
| | | | | | | | | | | | | | | | - Miguel Yzusqui
- Medicina Interna, Hospital Nuestra Señora del Prado. , Spain
| | - Sonia Casallo
- Medicina Interna, Hospital Nuestra Señora del Prado. , Spain
| | - María García
- Medicina Interna, Hospital General de Villarrobledo. , Spain
| | | | - Miguel Torralba
- Medicina Interna, Hospital Universitario, Guadalajara. , Spain
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How has the cost of antiretroviral therapy changed over the years? A database analysis in Italy. BMC Health Serv Res 2018; 18:691. [PMID: 30189882 PMCID: PMC6127985 DOI: 10.1186/s12913-018-3507-x] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/02/2018] [Accepted: 08/29/2018] [Indexed: 12/24/2022] Open
Abstract
Background The number of human immunodeficiency virus (HIV)-related hospitalizations has decreased worldwide in recent years, due to the availability of combined antiretroviral therapies (cART). The present analysis aimed to analyse the economic, and clinical burden of HIV management, after the introduction of systematic use of cART. Methods Data from HIV-infected patients, treated at Policlinico San Martino Hospital in Genova (Italy) were retrospectively collected. A comparison between years 2009 and 2015 was performed. HIV-related admissions were identified by using the Diagnosis-Related Group (DRG) codes. The resource consumption of outpatient services was derived by using a modelling approach. Expenditure for drugs was also analysed, as aggregate data. Results The number of HIV-infected patients was 898 in 2009 and 1006 in 2015. Overall, the virological success rate improved from 2009 to 2015, as the percentage of patients with HIV-RNA < 50 copies/mL increased from 79 to 89% (P < 0.05). The average incidence of hospitalizations per-patient decreased from 0.30 in 2009, to 0.13 in 2015. Average expenditure per-patient decreased from €10,107 in 2009 to €9063 in 2015. Conclusions The present analysis confirmed the role of cART in controlling HIV viral load and, consequently, in reducing hospitalizations, admissions to day-hospital and the use of outpatient services. Clinical improvements and economic savings more than compensated the investments required to treat HIV-infected patients with cART. Health Authorities should invest in modern cART supply and universal treatment, to use at best the available resources and obtain a cost-effective improvement of health in people living with HIV. Additional research, with the involvement of different centers and the use of patient-specific data, are recommended to consolidate the findings of this analysis. Electronic supplementary material The online version of this article (10.1186/s12913-018-3507-x) contains supplementary material, which is available to authorized users.
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Adverse Effects of Direct Acting Antivirals in HIV/HCV Coinfected Patients: A 4-Year Experience in Miami, Florida. Diseases 2018; 6:diseases6020051. [PMID: 29921760 PMCID: PMC6023459 DOI: 10.3390/diseases6020051] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/24/2018] [Revised: 06/16/2018] [Accepted: 06/18/2018] [Indexed: 12/20/2022] Open
Abstract
Introduction: The new direct acting antivirals (DAA) have demonstrated low rates of adverse effects in controlled studies. However, real world-studies have disclosed emerging toxicities and drug-drug interactions in special populations. Methods: We conducted a retrospective review of HIV/HCV coinfected patients who were treated with DAA at Jackson Memorial Hospital from 2014 to 2017. Our aim was to determine the adverse effects (AE) and factors that are associated with AE in HIV/HCV individuals who are treated with DAA. Results: There were 78 coinfected patients treated with DAA. AE that were secondary to DAA were reported by 21 (26.9%) patients. The most common AE were fatigue (47.6%), gastrointestinal symptoms (38.1%), anemia (14.3%), and headache (14.3%). In comparison with the rest of the study cohort, the patients who developed AE were more often Caucasian (33.3% vs. 10.5%, p = 0.017) and were more frequently treated with PrOD/Ribavirin (9.5% vs. 0%, p = 0.018). In terms of antiretroviral therapy (ART), there was a trend towards a more frequent use of TDF/FTC + NNRTI (33.3% vs. 14%, p = 0.055). Conclusions: These findings demonstrated good tolerability of DAAs in HIV/HCV coinfected patients. More real-world studies are needed to explore the variables that are associated with AE.
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Abstract
PURPOSE OF REVIEW Advances in diagnostic methods mean that co-infections are increasingly being detected in clinical practice, yet their significance is not always obvious. In parallel, basic science studies are increasingly investigating interactions between pathogens to try to explain real-life observations and elucidate biological mechanisms. RECENT FINDINGS Co-infections may be insignificant, detrimental, or even beneficial, and these outcomes can occur through multiple levels of interactions which include modulation of the host response, altering the performance of diagnostic tests, and drug-drug interactions during treatment. The harmful effects of chronic co-infections such as tuberculosis or Hepatitis B and C in association with HIV are well established, and recent studies have focussed on strategies to mitigate these effects. However, consequences of many acute co-infections are much less certain, and recent conflicting findings simply highlight many of the challenges of studying naturally acquired infections in humans. SUMMARY Tackling these challenges, using animal models, or careful prospective studies in humans may prove to be worthwhile. There are already tantalizing examples where identification and treatment of relevant co-infections seems to hold promise for improved health outcomes.
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Affiliation(s)
| | - Anna Turkova
- MRC Clinical Trials Unit, Institute of Clinical Trials and Methodology, University College London
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Sacks-Davis R, Pedrana AE, Scott N, Doyle JS, Hellard ME. Eliminating HIV/HCV co-infection in gay and bisexual men: is it achievable through scaling up treatment? Expert Rev Anti Infect Ther 2018; 16:411-422. [PMID: 29722275 DOI: 10.1080/14787210.2018.1471355] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Abstract
INTRODUCTION Broad availability of direct-acting antiviral therapy for hepatitis C virus (HCV) raises the possibility that HCV prevalence and incidence can be reduced through scaling-up treatment, leading to the elimination of HCV. High rates of linkage to HIV care among HIV-infected gay and bisexual men may facilitate high uptake of HCV treatment, possibly making HCV elimination more achievable in this group. Areas covered: This review covers HCV elimination in HIV-infected gay and bisexual men, including epidemiology, spontaneous clearance and long term sequelae in the absence of direct-acting antiviral therapy; direct-acting antiviral therapy uptake and effectiveness in this group; HCV reinfection following successful treatment; and areas for further research. Expert commentary: Early data from the direct-acting antiviral era suggest that treatment uptake is increasing among HIV infected GBM, and SVR rates are very promising. However, in order to sustain current treatment rates, additional interventions at the behavioral, physician, and structural levels may be required to increase HCV diagnosis, including prompt detection of HCV reinfection. Timely consideration of these issues is required to maximize the population-level impact of HCV direct-acting antiviral therapy. Potential HCV transmissions from HIV-uninfected GBM, across international borders, and from those who are not GBM also warrant consideration.
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Affiliation(s)
- Rachel Sacks-Davis
- a Disease Elimination Program , Burnet Institute , Melbourne , Australia.,b Department of Medicine , University of Melbourne , Parkville , Australia
| | - Alisa E Pedrana
- a Disease Elimination Program , Burnet Institute , Melbourne , Australia.,c Department of Epidemiology and Preventive Medicine , Monash University , Melbourne , Australia
| | - Nick Scott
- a Disease Elimination Program , Burnet Institute , Melbourne , Australia.,c Department of Epidemiology and Preventive Medicine , Monash University , Melbourne , Australia
| | - Joseph S Doyle
- a Disease Elimination Program , Burnet Institute , Melbourne , Australia.,d Central Clinical School , Monash University , Melbourne , Australia
| | - Margaret E Hellard
- a Disease Elimination Program , Burnet Institute , Melbourne , Australia.,c Department of Epidemiology and Preventive Medicine , Monash University , Melbourne , Australia
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Deng H, Deng X, Liu Y, Xu Y, Lan Y, Gao M, Xu M, Gao H, Wu X, Liao B, Chen W, Zhao M, Hu F, Wang Z. Naturally occurring antiviral drug resistance in HIV patients who are mono-infected or co-infected with HBV or HCV in China. J Med Virol 2018; 90:1246-1256. [PMID: 29574921 DOI: 10.1002/jmv.25078] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/12/2018] [Accepted: 03/15/2018] [Indexed: 12/14/2022]
Abstract
Drug resistance mutations (DRMs) may reduce the efficacy of antiviral therapy. However, the studies focused on naturally occurring, pre-existing DRMs among co-infected patients in China are limited. To investigate DRMs prevalence in treatment-naïve human immunodeficiency virus (HIV), hepatitis B virus (HBV), and hepatitis C virus (HCV) mono- and co-infected patients in China, a total of 570 patients were recruited for this study. DRMs sequences were amplified and successfully sequenced in 481 of these patients, who were grouped into three cohorts: (i) The HBV cohort included 100 HIV/HBV co-infected and 110 HBV mono-infected patients who were sequenced for HBV; (ii) The HCV cohort included 91 patients who were HIV/HCV co-infected and 72 who were HCV mono-infected for HCV sequencing; and (iii) The HIV cohort included 39 HIV mono-infected, 22 HIV/HCV, and 47 HIV/HBV co-infected patients for HIV sequencing. Next-generation sequencing and Sanger sequencing were used in this study. The results showed that in the HCV cohort, HCV genotypes 6a (P < 0.001) and 3b (P = 0.004) were more prevalent in HIV/HCV co-infected patients, however, the prevalence of HBV and HIV genotypes were similar within the HBV and HIV cohorts. HBV DRMs prevalence was significantly higher in HIV/HBV co-infected than HBV mono-infected patients (8.0% vs 0.9%, P = 0.015), whereas HCV and HIV DRMs did not differ within the HCV and HIV cohort (P > 0.05). This study revealed that HBV DRMs were more prevalent in HIV/HBV co-infected patients in China, while DRMs in HCV and HIV patients did not differ. Further dynamic surveillance of DRMs may be needed.
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Affiliation(s)
- Haohui Deng
- State Key Laboratory of Organ Failure Research, Guangdong Provincial Key Laboratory of Viral Hepatitis Research, Department of Infectious Diseases, Nanfang Hospital, Southern Medical University, Guangzhou, China.,Department of Infectious Diseases, Guangzhou Eight People's Hospital, Guangzhou Medical University, Guangzhou, China
| | - Xizi Deng
- Department of Infectious Diseases, Guangzhou Eight People's Hospital, Guangzhou Medical University, Guangzhou, China
| | - Yu Liu
- State Key Laboratory of Organ Failure Research, Guangdong Provincial Key Laboratory of Viral Hepatitis Research, Department of Infectious Diseases, Nanfang Hospital, Southern Medical University, Guangzhou, China
| | - Ying Xu
- State Key Laboratory of Organ Failure Research, Guangdong Provincial Key Laboratory of Viral Hepatitis Research, Department of Infectious Diseases, Nanfang Hospital, Southern Medical University, Guangzhou, China
| | - Yun Lan
- Department of Infectious Diseases, Guangzhou Eight People's Hospital, Guangzhou Medical University, Guangzhou, China
| | - Ming Gao
- Department of Infectious Diseases, Guangzhou Eight People's Hospital, Guangzhou Medical University, Guangzhou, China
| | - Min Xu
- Department of Infectious Diseases, Guangzhou Eight People's Hospital, Guangzhou Medical University, Guangzhou, China
| | - Hongbo Gao
- Department of Infectious Diseases, Guangzhou Eight People's Hospital, Guangzhou Medical University, Guangzhou, China
| | - Xiexing Wu
- Department of Infectious Diseases, Guangzhou Eight People's Hospital, Guangzhou Medical University, Guangzhou, China
| | - Baolin Liao
- Department of Infectious Diseases, Guangzhou Eight People's Hospital, Guangzhou Medical University, Guangzhou, China
| | - Weilie Chen
- Department of Infectious Diseases, Guangzhou Eight People's Hospital, Guangzhou Medical University, Guangzhou, China
| | - Miaoxian Zhao
- State Key Laboratory of Organ Failure Research, Guangdong Provincial Key Laboratory of Viral Hepatitis Research, Department of Infectious Diseases, Nanfang Hospital, Southern Medical University, Guangzhou, China
| | - Fengyu Hu
- Department of Infectious Diseases, Guangzhou Eight People's Hospital, Guangzhou Medical University, Guangzhou, China
| | - Zhanhui Wang
- State Key Laboratory of Organ Failure Research, Guangdong Provincial Key Laboratory of Viral Hepatitis Research, Department of Infectious Diseases, Nanfang Hospital, Southern Medical University, Guangzhou, China
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Taramasso L, Di Biagio A, Bovis F, Nicolini LA, Antinori A, Milazzo L, Sollima S, Gubertini G, Niero F, Saracino A, Bruno R, Borghi V, Montagnani F, Cattelan A, Hasson H, Taliani G, D’Arminio Monforte A, Mastroianni C, Di Perri G, Bigoni S, Puoti M, Spinetti A, Gori A, Boffa N, Cacopardo B, Giacometti A, Parruti G, Vullo V, Chirianni A, Teti E, Pasquazzi C, Segala D, Andreoni M. Trend of estimated glomerular filtration rate during ombistasvir/paritaprevir/ritonavir plus dasabuvir ± ribavirin in HIV/HCV co-infected patients. PLoS One 2018; 13:e0192627. [PMID: 29462201 PMCID: PMC5819795 DOI: 10.1371/journal.pone.0192627] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/04/2017] [Accepted: 01/26/2018] [Indexed: 12/13/2022] Open
Abstract
The renal function is a key-issue in HIV/HCV co-infected patients, nevertheless, it has not established so far whether HCV treatment with new direct acting agents could impact on estimated glomerular filtration rate (eGFR) variations. In the present work, we examined the real-life data on renal function that have been prospectively collected in the SIMIT compassionate-use program of ombitasvir/paritaprevir/ritonavir plus dasabuvir (OBV/PTV/r + DSV) in 144 HIV/HCV genotype 1 co-infected patients. The population was 74% male, 30.5% in CDC stage C, with median age of 52 years (48.0-56.5) and median liver stiffness of 7.8 kPa (6.7-9.2). Median baseline eGFR was 102.0 (90.8-108.1), changing to 99.8 (83.5-104.8) at the end of treatment (EoT), and 100.0 (87.3-105.6) 12 weeks after the EoT (FU12), p<0.0001. No patient had grade 3-4 increase of creatinine. At EoT 60/144 (41.7%) patients had ≥ 5% reduction in their eGFR, confirmed at FU12 in 39/60 (65.0%) cases. Longer duration of HCV infection (cut-off 12.9 years), lower HCV-RNA viral load (cut-off 1,970,160 IU/ml) and lower platelet count (cut-off 167,000 x106/L) were significantly associated with eGFR decline at logistic analysis (adjOR 2.9, 95%CI 1.0-8.8, p = 0.05; adjOR 3.5, 95%CI 1.2-10.4, p = 0.02; adjOR 2.8, 95%CI 1.1-6.8, p = 0.03, respectively). After repeating the analysis throughout a mixed model, a higher eGFR decline was highlighted in patients concomitantly treated with tenofovir (p = 0.0001), ribavirin (p = 0.0001), or integrase inhibitors (p <0.0001), with longer duration of HIV (p = 0.0002) and HCV infection (p = 0.035), lower baseline HCV RNA (p <0.0001), previous HCV treatment (p<0.0001), and older age (p<0.0001). In conclusion, our study confirms a good renal safety profile of OBV/PTV/r + DSV treatment in HIV/HCV patients, and the median decline of 2 ml/min in eGFR, albeit statistically significant, is of doubtful clinical significance. The role of aging, concomitant therapies and duration of HIV/HCV infection needs to be further investigated.
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Affiliation(s)
- Lucia Taramasso
- University of Genova (DISSAL), Infectious Diseases Clinic, Policlinico Hospital San Martino, Genova, Italy
| | - Antonio Di Biagio
- Infectious Diseases Clinic, Policlinico Hospital San Martino, Genova, Italy
- * E-mail:
| | - Francesca Bovis
- Biostatistics Unit, Department of Health Sciences, University of Genoa, Genoa, Italy
| | - Laura Ambra Nicolini
- University of Genova (DISSAL), Infectious Diseases Clinic, Policlinico Hospital San Martino, Genova, Italy
| | - Andrea Antinori
- Clinical Department, National Institute for Infectious Diseases, INMI L. Spallanzani, Rome, Italy
| | - Laura Milazzo
- Department of Biomedical and Clinical Science, University of Milan, Milan, Italy
| | - Salvatore Sollima
- Department of Biomedical and Clinical Science, University of Milan, Milan, Italy
| | - Guido Gubertini
- 1st Division of Infectious Diseases, ASST Fatebenefratelli-Sacco, Milan, Italy
| | - Fosca Niero
- 1st Division of Infectious Diseases, ASST Fatebenefratelli-Sacco, Milan, Italy
| | | | - Raffaele Bruno
- Division of Infectious and Tropical Diseases, IRCCS Policlinico San Matteo, Pavia, Italy
| | - Vanni Borghi
- Infectious Diseases Clinic, University Hospital, Modena, Italy
| | - Francesca Montagnani
- Department of Internal and Specialty Medicine University Infectious Diseases Unit, AOU Senese, Siena, Italy
| | - Annamaria Cattelan
- Department of Infectious and Tropical Diseases, University Hospital, Padova, Italy
| | - Hamid Hasson
- Department of Infectious Diseases, San Raffaele Scientific Institute, Milan, Italy
| | - Gloria Taliani
- Department of Clinical Medicine, Policlinico Umberto I, Sapienza University of Rome, Rome, Italy
| | | | - Claudio Mastroianni
- Infectious Diseases Unit, Sapienza University of Rome, Latina, Italy, and Department of Public Health and Infectious Diseases, Policlinico Umberto I, Sapienza University of Rome, Rome, Italy
| | - Giovanni Di Perri
- Unit of Infectious Diseases, University of Turin, Department of Medical Sciences, Amedeo di Savoia Hospital, Turin, Italy
| | - Sara Bigoni
- Division of Infectious Diseases, AO Papa Giovanni XXIII, Bergamo, Italy
| | - Massimo Puoti
- Division of Infectious Diseases, AO Niguarda Ca' Granda Hospital, Milan, Italy
| | - Angiola Spinetti
- Division of Infectious and Tropical Diseases, University of Brescia and Spedali Civili General Hospital, Brescia, Italy
| | - Andrea Gori
- Division of Infectious Diseases, Department of Internal Medicine, San Gerardo Hospital, University of Milan-Bicocca, Milan, Italy
| | - Nicola Boffa
- First Division of Infectious Diseases, S. Giovanni di Dio e Ruggi d'Aragona Hospital, Salerno, Italy
| | - Bruno Cacopardo
- Division of Infectious Diseases, Department of Clinical and Experimental Medicine, ARNAS Garibaldi Hospital, University of Catania, Catania, Italy
| | - Andrea Giacometti
- Infectious Diseases Unit, Department of Biomedical Sciences and Public Health, Marche Polytechnic University c/o Ospedali Riuniti, Ancona, Italy
| | - Giustino Parruti
- Infectious Disease Unit, Pescara General Hospital, Pescara, Italy
| | - Vincenzo Vullo
- Department of Public Health and Infectious Diseases, Policlinico Umberto I, Sapienza University of Rome, Rome, Italy
| | | | - Elisabetta Teti
- Clinical Infectious Diseases, Department. of Systems Medicine, Tor Vergata University, Rome, Italy
| | - Caterina Pasquazzi
- Clinical Infectious Diseases, Sant'Andrea Hospital—Sapienza University of Rome, Rome, Italy
| | - Daniela Segala
- Unit of Infectious Diseases, University Hospital of Ferrara, Ferrara, Italy
| | - Massimo Andreoni
- Clinical Infectious Diseases, Department. of Systems Medicine, Tor Vergata University, Rome, Italy
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