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For: Cassol E, Malfeld S, Mahasha P, van der Merwe S, Cassol S, Seebregts C, Alfano M, Poli G, Rossouw T. Persistent microbial translocation and immune activation in HIV-1-infected South Africans receiving combination antiretroviral therapy. J Infect Dis 2010;202:723-33. [PMID: 20629534 DOI: 10.1086/655229] [Citation(s) in RCA: 166] [Impact Index Per Article: 11.1] [Reference Citation Analysis] [What about the content of this article? (0)] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/07/2023] Open

For:	Cassol E, Malfeld S, Mahasha P, van der Merwe S, Cassol S, Seebregts C, Alfano M, Poli G, Rossouw T. Persistent microbial translocation and immune activation in HIV-1-infected South Africans receiving combination antiretroviral therapy. J Infect Dis 2010;202:723-33. [PMID: 20629534 DOI: 10.1086/655229] [Citation(s) in RCA: 166] [Impact Index Per Article: 11.1] [Reference Citation Analysis] [What about the content of this article? (0)] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/07/2023] Open

Number

Cited by Other Article(s)

Raehtz KD, Pandrea I, Apetrei C. It's all in the gut: the central role of the gut and microbiome in preventing disease progression in simian immunodeficiency viruses infected African nonhuman primates. Curr Opin HIV AIDS 2025;20:124-132. [PMID: 39774258 PMCID: PMC11802300 DOI: 10.1097/coh.0000000000000911] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/11/2025]

Xiao Q, Yu F, Yan L, Lao X, Liang X, Zhao H, Zhai L, Yang Z, Zhang X, Liu Y, Zhang F. The CD4/CD8 ratio is associated with T lymphocyte functions in long-term virally suppressed patients with HIV. BMC Infect Dis 2025;25:76. [PMID: 39825235 PMCID: PMC11740514 DOI: 10.1186/s12879-025-10469-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/03/2023] [Accepted: 01/09/2025] [Indexed: 01/20/2025] Open

Abi N, Young A, Tiwari P, Chen J, Liu C, Hui Q, So-Armah K, Freiberg MS, Justice AC, Xu K, Gwinn M, Marconi VC, Sun YV. Epigenome-Wide and Methylation Risk Score Analysis of Body Mass Index Among People with HIV. EPIGENOMES 2024;8:46. [PMID: 39727808 PMCID: PMC11675887 DOI: 10.3390/epigenomes8040046] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/05/2024] [Revised: 10/25/2024] [Accepted: 12/03/2024] [Indexed: 12/28/2024] Open

Affiliation(s)

Nanzha Abi Department of Epidemiology, Rollins School of Public Health, Emory University, Atlanta, GA 30322, USA; (N.A.); (A.Y.); (P.T.); (J.C.); (C.L.); (Q.H.); (M.G.)
Alexandra Young Department of Epidemiology, Rollins School of Public Health, Emory University, Atlanta, GA 30322, USA; (N.A.); (A.Y.); (P.T.); (J.C.); (C.L.); (Q.H.); (M.G.)
Pradeep Tiwari Department of Epidemiology, Rollins School of Public Health, Emory University, Atlanta, GA 30322, USA; (N.A.); (A.Y.); (P.T.); (J.C.); (C.L.); (Q.H.); (M.G.) Atlanta Veterans Affairs Health Care System, Decatur, GA 30033, USA
Junyu Chen Department of Epidemiology, Rollins School of Public Health, Emory University, Atlanta, GA 30322, USA; (N.A.); (A.Y.); (P.T.); (J.C.); (C.L.); (Q.H.); (M.G.)
Chang Liu Department of Epidemiology, Rollins School of Public Health, Emory University, Atlanta, GA 30322, USA; (N.A.); (A.Y.); (P.T.); (J.C.); (C.L.); (Q.H.); (M.G.)
Qin Hui Department of Epidemiology, Rollins School of Public Health, Emory University, Atlanta, GA 30322, USA; (N.A.); (A.Y.); (P.T.); (J.C.); (C.L.); (Q.H.); (M.G.)
Kaku So-Armah Boston University School of Medicine, Boston, MA 02118, USA;
Matthew S. Freiberg Cardiovascular Medicine Division, Vanderbilt University School of Medicine and Tennessee Valley Healthcare System, Nashville, TN 37212, USA;
Amy C. Justice Connecticut Veteran Health System, West Haven, CT 06516, USA; (A.C.J.); (K.X.) Schools of Medicine and Public Health, Yale University, New Haven, CT 06520, USA
Ke Xu Connecticut Veteran Health System, West Haven, CT 06516, USA; (A.C.J.); (K.X.) Department of Psychiatry, Yale School of Medicine, New Haven, CT 06520, USA
Marta Gwinn Department of Epidemiology, Rollins School of Public Health, Emory University, Atlanta, GA 30322, USA; (N.A.); (A.Y.); (P.T.); (J.C.); (C.L.); (Q.H.); (M.G.)
Vincent C. Marconi Atlanta Veterans Affairs Health Care System, Decatur, GA 30033, USA Hubert Department of Global Health, Rollins School of Public Health, Emory University, Atlanta, GA 30322, USA Division of Infectious Diseases, Emory University School of Medicine, Atlanta, GA 30322, USA
Yan V. Sun Department of Epidemiology, Rollins School of Public Health, Emory University, Atlanta, GA 30322, USA; (N.A.); (A.Y.); (P.T.); (J.C.); (C.L.); (Q.H.); (M.G.) Atlanta Veterans Affairs Health Care System, Decatur, GA 30033, USA

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Mac Cann R, Newman E, Devane D, Sabin C, Cotter AG, Landay A, O’Toole PW, Mallon PW. HIV, the gut microbiome and clinical outcomes, a systematic review. PLoS One 2024;19:e0308859. [PMID: 39652612 PMCID: PMC11627425 DOI: 10.1371/journal.pone.0308859] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/15/2024] [Accepted: 08/01/2024] [Indexed: 12/12/2024] Open

Capriotti Z, Klase Z. Innate immune memory in chronic HIV and HIV-associated neurocognitive disorders (HAND): potential mechanisms and clinical implications. J Neurovirol 2024;30:451-476. [PMID: 39733092 PMCID: PMC11846772 DOI: 10.1007/s13365-024-01239-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/19/2024] [Revised: 11/26/2024] [Accepted: 12/13/2024] [Indexed: 12/30/2024]

Mboumba Bouassa RS, Needham J, Nohynek D, Samarani S, Bobeuf F, Del Balso L, Paisible N, Vertzagias C, Sebastiani G, Margolese S, Mandarino E, Singer J, Klein M, Lebouché B, Cox J, Vulesevic B, Müller A, Lau E, Routy JP, Jenabian MA, Costiniuk CT. Feasibility of a Randomized, Interventional Pilot Clinical Study of Oral Cannabinoids in People with HIV on Antiretroviral Therapy: CTNPT 028. J Pers Med 2024;14:745. [PMID: 39063999 PMCID: PMC11277849 DOI: 10.3390/jpm14070745] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/27/2024] [Revised: 07/02/2024] [Accepted: 07/09/2024] [Indexed: 07/28/2024] Open

Affiliation(s)

Ralph-Sydney Mboumba Bouassa Department of Biological Sciences and CERMO-FC Research Centre, Université du Québec à Montréal, Montreal, QC H2X 3Y7, Canada; (R.-S.M.B.); (M.-A.J.) Infectious Diseases and Immunity in Global Health Program, Research Institute of the McGill University Health Centre, Montreal, QC H4A 3J1, Canada; (S.S.); (C.V.); (G.S.); (M.K.); (B.L.); (J.C.); (B.V.); (J.-P.R.)
Judy Needham Canadian HIV Trials Network, Vancouver, BC V6Z 1Y6, Canada; (J.N.); (D.N.); (S.M.); (E.M.); (J.S.); (A.M.); (E.L.) Centre for Advancing Health Outcomes, St. Paul’s Hospital, Vancouver, BC V6Z 1Y6, Canada
Dana Nohynek Canadian HIV Trials Network, Vancouver, BC V6Z 1Y6, Canada; (J.N.); (D.N.); (S.M.); (E.M.); (J.S.); (A.M.); (E.L.) Centre for Advancing Health Outcomes, St. Paul’s Hospital, Vancouver, BC V6Z 1Y6, Canada
Suzanne Samarani Infectious Diseases and Immunity in Global Health Program, Research Institute of the McGill University Health Centre, Montreal, QC H4A 3J1, Canada; (S.S.); (C.V.); (G.S.); (M.K.); (B.L.); (J.C.); (B.V.); (J.-P.R.) Department of Medicine, Division of Infectious Diseases and Chronic Viral Illnesses Service, McGill University Health Centre, Montreal, QC H4A 3J1, Canada; (F.B.); (L.D.B.); (N.P.)
Florian Bobeuf Department of Medicine, Division of Infectious Diseases and Chronic Viral Illnesses Service, McGill University Health Centre, Montreal, QC H4A 3J1, Canada; (F.B.); (L.D.B.); (N.P.)
Lina Del Balso Department of Medicine, Division of Infectious Diseases and Chronic Viral Illnesses Service, McGill University Health Centre, Montreal, QC H4A 3J1, Canada; (F.B.); (L.D.B.); (N.P.)
Natalie Paisible Department of Medicine, Division of Infectious Diseases and Chronic Viral Illnesses Service, McGill University Health Centre, Montreal, QC H4A 3J1, Canada; (F.B.); (L.D.B.); (N.P.)
Claude Vertzagias Infectious Diseases and Immunity in Global Health Program, Research Institute of the McGill University Health Centre, Montreal, QC H4A 3J1, Canada; (S.S.); (C.V.); (G.S.); (M.K.); (B.L.); (J.C.); (B.V.); (J.-P.R.) Department of Medicine, Division of Infectious Diseases and Chronic Viral Illnesses Service, McGill University Health Centre, Montreal, QC H4A 3J1, Canada; (F.B.); (L.D.B.); (N.P.)
Giada Sebastiani Infectious Diseases and Immunity in Global Health Program, Research Institute of the McGill University Health Centre, Montreal, QC H4A 3J1, Canada; (S.S.); (C.V.); (G.S.); (M.K.); (B.L.); (J.C.); (B.V.); (J.-P.R.) Department of Medicine, Division of Infectious Diseases and Chronic Viral Illnesses Service, McGill University Health Centre, Montreal, QC H4A 3J1, Canada; (F.B.); (L.D.B.); (N.P.) Department of Medicine, Division of Gastroenterology and Hepatology, McGill University Health Centre, Montreal, QC H4A 3J1, Canada
Shari Margolese Canadian HIV Trials Network, Vancouver, BC V6Z 1Y6, Canada; (J.N.); (D.N.); (S.M.); (E.M.); (J.S.); (A.M.); (E.L.)
Enrico Mandarino Canadian HIV Trials Network, Vancouver, BC V6Z 1Y6, Canada; (J.N.); (D.N.); (S.M.); (E.M.); (J.S.); (A.M.); (E.L.)
Joel Singer Canadian HIV Trials Network, Vancouver, BC V6Z 1Y6, Canada; (J.N.); (D.N.); (S.M.); (E.M.); (J.S.); (A.M.); (E.L.) Centre for Advancing Health Outcomes, St. Paul’s Hospital, Vancouver, BC V6Z 1Y6, Canada School of Population and Public Health, University of British Columbia, Vancouver, BC V6T 1Z4, Canada
Marina Klein Infectious Diseases and Immunity in Global Health Program, Research Institute of the McGill University Health Centre, Montreal, QC H4A 3J1, Canada; (S.S.); (C.V.); (G.S.); (M.K.); (B.L.); (J.C.); (B.V.); (J.-P.R.) Department of Medicine, Division of Infectious Diseases and Chronic Viral Illnesses Service, McGill University Health Centre, Montreal, QC H4A 3J1, Canada; (F.B.); (L.D.B.); (N.P.)
Bertrand Lebouché Infectious Diseases and Immunity in Global Health Program, Research Institute of the McGill University Health Centre, Montreal, QC H4A 3J1, Canada; (S.S.); (C.V.); (G.S.); (M.K.); (B.L.); (J.C.); (B.V.); (J.-P.R.) Department of Medicine, Division of Infectious Diseases and Chronic Viral Illnesses Service, McGill University Health Centre, Montreal, QC H4A 3J1, Canada; (F.B.); (L.D.B.); (N.P.) Department of Family Medicine, McGill University Health Centre, Montreal, QC H4A 3J1, Canada Canadian Institutes of Health Research Strategy for Patient-Oriented Research Mentorship Chair in Innovative Clinical Trials, Montreal, QC H4A 3J1, Canada
Joseph Cox Infectious Diseases and Immunity in Global Health Program, Research Institute of the McGill University Health Centre, Montreal, QC H4A 3J1, Canada; (S.S.); (C.V.); (G.S.); (M.K.); (B.L.); (J.C.); (B.V.); (J.-P.R.) Department of Medicine, Division of Infectious Diseases and Chronic Viral Illnesses Service, McGill University Health Centre, Montreal, QC H4A 3J1, Canada; (F.B.); (L.D.B.); (N.P.)
Branka Vulesevic Infectious Diseases and Immunity in Global Health Program, Research Institute of the McGill University Health Centre, Montreal, QC H4A 3J1, Canada; (S.S.); (C.V.); (G.S.); (M.K.); (B.L.); (J.C.); (B.V.); (J.-P.R.) Department of Medicine, Division of Infectious Diseases and Chronic Viral Illnesses Service, McGill University Health Centre, Montreal, QC H4A 3J1, Canada; (F.B.); (L.D.B.); (N.P.)
Alison Müller Canadian HIV Trials Network, Vancouver, BC V6Z 1Y6, Canada; (J.N.); (D.N.); (S.M.); (E.M.); (J.S.); (A.M.); (E.L.) Centre for Advancing Health Outcomes, St. Paul’s Hospital, Vancouver, BC V6Z 1Y6, Canada
Elisa Lau Canadian HIV Trials Network, Vancouver, BC V6Z 1Y6, Canada; (J.N.); (D.N.); (S.M.); (E.M.); (J.S.); (A.M.); (E.L.) Centre for Advancing Health Outcomes, St. Paul’s Hospital, Vancouver, BC V6Z 1Y6, Canada
Jean-Pierre Routy Infectious Diseases and Immunity in Global Health Program, Research Institute of the McGill University Health Centre, Montreal, QC H4A 3J1, Canada; (S.S.); (C.V.); (G.S.); (M.K.); (B.L.); (J.C.); (B.V.); (J.-P.R.) Department of Medicine, Division of Infectious Diseases and Chronic Viral Illnesses Service, McGill University Health Centre, Montreal, QC H4A 3J1, Canada; (F.B.); (L.D.B.); (N.P.) Department of Medicine, Division of Hematology, McGill University Health Centre, Montreal, QC H4A 3J1, Canada
Mohammad-Ali Jenabian Department of Biological Sciences and CERMO-FC Research Centre, Université du Québec à Montréal, Montreal, QC H2X 3Y7, Canada; (R.-S.M.B.); (M.-A.J.)
Cecilia T. Costiniuk Infectious Diseases and Immunity in Global Health Program, Research Institute of the McGill University Health Centre, Montreal, QC H4A 3J1, Canada; (S.S.); (C.V.); (G.S.); (M.K.); (B.L.); (J.C.); (B.V.); (J.-P.R.) Department of Medicine, Division of Infectious Diseases and Chronic Viral Illnesses Service, McGill University Health Centre, Montreal, QC H4A 3J1, Canada; (F.B.); (L.D.B.); (N.P.) Division of Experimental Medicine, McGill University, Montreal, QC H4A 3J1, Canada

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Hmiel L, Zhang S, Obare LM, Santana MADO, Wanjalla CN, Titanji BK, Hileman CO, Bagchi S. Inflammatory and Immune Mechanisms for Atherosclerotic Cardiovascular Disease in HIV. Int J Mol Sci 2024;25:7266. [PMID: 39000373 PMCID: PMC11242562 DOI: 10.3390/ijms25137266] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/01/2024] [Revised: 06/26/2024] [Accepted: 06/28/2024] [Indexed: 07/16/2024] Open

Planchais C, Molinos-Albert LM, Rosenbaum P, Hieu T, Kanyavuz A, Clermont D, Prazuck T, Lefrou L, Dimitrov JD, Hüe S, Hocqueloux L, Mouquet H. HIV-1 treatment timing shapes the human intestinal memory B-cell repertoire to commensal bacteria. Nat Commun 2023;14:6326. [PMID: 37816704 PMCID: PMC10564866 DOI: 10.1038/s41467-023-42027-6] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/22/2023] [Accepted: 09/28/2023] [Indexed: 10/12/2023] Open

Hussain MA, Watson CWM, Morgan EE, Heaton RK, Letendre SL, Jeste DV, Moore DJ, Iudicello JE. Combined effects of loneliness and inflammation on depression in people with HIV. J Neurovirol 2023;29:538-554. [PMID: 37651083 PMCID: PMC10645641 DOI: 10.1007/s13365-023-01145-z] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/17/2022] [Revised: 04/17/2023] [Accepted: 04/24/2023] [Indexed: 09/01/2023]

Abstract

OBJECTIVE

Loneliness is prevalent in people with HIV (PWH) and associated with adverse health-related consequences, including depression. Chronic inflammation has been linked to depression in PWH, though its association with loneliness is less well established. Simultaneous examination of inflammation, loneliness and depression is needed to clarify these relationships. This study investigated the relationship between loneliness and inflammation, and the effects of loneliness and inflammation on depression in PWH.

METHODS

82 PWH who were on suppressive ART (mean age [SD] = 53.2 [9.0]) completed the UCLA Loneliness Scale-Version 3 and the Center for Epidemiologic Studies Depression Scale as part of a comprehensive evaluation. Biomarkers of systemic inflammation (CRP, IL-6, CCL2/MCP-1, sCD14) and coagulation (D-dimer) were measured in blood using commercial immunoassays.

RESULTS

Multivariable linear regression analyses revealed that higher D-dimer, CCL2/MCP-1, and sCD14 were significant predictors of loneliness (ps < .05) while accounting for relevant covariates. Stepwise multiple linear regression models that included loneliness, biomarkers, and their interactions as predictors of depressive symptoms revealed significant main effects of loneliness and CCL2/MCP-1 levels (ps < .05), and a significant loneliness by D-dimer interaction (p < .05) whereby higher D-dimer was associated with increased depressive symptoms only at higher levels of loneliness.

CONCLUSIONS

Increased coagulation activity is associated with loneliness, and in the context of loneliness, may increase risk for depression. Increased inflammation was associated with depression suggesting potentially dissociable underlying biological processes. To the extent that these processes are modifiable, such findings could have important implications in the treatment of loneliness and depression in PWH.

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Krug SM, Grünhagen C, Allers K, Bojarski C, Seybold J, Schneider T, Schulzke JD, Epple HJ. Macromolecule Translocation across the Intestinal Mucosa of HIV-Infected Patients by Transcytosis and through Apoptotic Leaks. Cells 2023;12:1887. [PMID: 37508551 PMCID: PMC10378197 DOI: 10.3390/cells12141887] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/16/2023] [Revised: 07/13/2023] [Accepted: 07/14/2023] [Indexed: 07/30/2023] Open

Cummings MJ, Bakamutumaho B, Price A, Owor N, Kayiwa J, Namulondo J, Byaruhanga T, Jain K, Postler TS, Muwanga M, Nsereko C, Nayiga I, Kyebambe S, Che X, Sameroff S, Tokarz R, Shah SS, Larsen MH, Lipkin WI, Lutwama JJ, O’Donnell MR. HIV infection drives pro-inflammatory immunothrombotic pathway activation and organ dysfunction among adults with sepsis in Uganda. AIDS 2023;37:233-245. [PMID: 36355913 PMCID: PMC9780191 DOI: 10.1097/qad.0000000000003410] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/12/2022]

Abstract

BACKGROUND

The global burden of sepsis is concentrated in high HIV-burden settings in sub-Saharan Africa (SSA). Despite this, little is known about the immunopathology of sepsis in persons with HIV (PWH) in the region. We sought to determine the influence of HIV on host immune responses and organ dysfunction among adults hospitalized with suspected sepsis in Uganda.

DESIGN

Prospective cohort study.

METHODS

We compared organ dysfunction and 30-day outcome profiles of PWH and those without HIV. We quantified 14 soluble immune mediators, reflective of key domains of sepsis immunopathology, and performed whole-blood RNA-sequencing on samples from a subset of patients. We used propensity score methods to match PWH and those without HIV by demographics, illness duration, and clinical severity, and compared immune mediator concentrations and gene expression profiles across propensity score-matched groups.

RESULTS

Among 299 patients, 157 (52.5%) were PWH (clinical stage 3 or 4 in 80.3%, 67.7% with known HIV on antiretroviral therapy). PWH presented with more severe physiologic derangement and shock, and had higher 30-day mortality (34.5% vs. 10.2%; P < 0.001). Across propensity score-matched groups, PWH exhibited greater pro-inflammatory immune activation, including upregulation of interleukin (IL)-6, IL-8, IL-15, IL-17 and HMGB1 signaling, with concomitant T-cell exhaustion, prothrombotic pathway activation, and angiopoeitin-2-related endothelial dysfunction.

CONCLUSIONS

Sepsis-related organ dysfunction and mortality in Uganda disproportionately affect PWH, who demonstrate exaggerated activation of multiple immunothrombotic and metabolic pathways implicated in sepsis pathogenesis. Further investigations are needed to refine understanding of sepsis immunopathology in PWH, particularly mechanisms amenable to therapeutic manipulation.

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Affiliation(s)

Matthew J. Cummings Division of Pulmonary, Allergy, and Critical Care Medicine, Department of Medicine, Vagelos College of Physicians and Surgeons, Columbia University, New York, NY, USA Center for Infection and Immunity, Mailman School of Public Health, Columbia University, New York, NY, USA
Barnabas Bakamutumaho Department of Arbovirology, Emerging and Re-emerging Infectious Diseases, Uganda Virus Research Institute, Entebbe, Uganda Immunizable Diseases Unit, Uganda Virus Research Institute, Entebbe, Uganda
Adam Price Center for Infection and Immunity, Mailman School of Public Health, Columbia University, New York, NY, USA
Nicholas Owor Department of Arbovirology, Emerging and Re-emerging Infectious Diseases, Uganda Virus Research Institute, Entebbe, Uganda
John Kayiwa Department of Arbovirology, Emerging and Re-emerging Infectious Diseases, Uganda Virus Research Institute, Entebbe, Uganda
Joyce Namulondo Department of Arbovirology, Emerging and Re-emerging Infectious Diseases, Uganda Virus Research Institute, Entebbe, Uganda
Timothy Byaruhanga Department of Arbovirology, Emerging and Re-emerging Infectious Diseases, Uganda Virus Research Institute, Entebbe, Uganda
Komal Jain Center for Infection and Immunity, Mailman School of Public Health, Columbia University, New York, NY, USA
Thomas S. Postler Department of Microbiology and Immunology, Vagelos College of Physicians and Surgeons, Columbia University, New York, NY, USA
Moses Muwanga Entebbe General Referral Hospital, Ministry of Health, Entebbe, Uganda
Christopher Nsereko Entebbe General Referral Hospital, Ministry of Health, Entebbe, Uganda
Irene Nayiga Entebbe General Referral Hospital, Ministry of Health, Entebbe, Uganda
Stephen Kyebambe Entebbe General Referral Hospital, Ministry of Health, Entebbe, Uganda
Xiaoyu Che Center for Infection and Immunity, Mailman School of Public Health, Columbia University, New York, NY, USA Department of Biostatistics, Mailman School of Public Health, Columbia University, New York, NY, USA
Stephen Sameroff Center for Infection and Immunity, Mailman School of Public Health, Columbia University, New York, NY, USA
Rafal Tokarz Center for Infection and Immunity, Mailman School of Public Health, Columbia University, New York, NY, USA
Shivang S. Shah Division of Infectious Diseases, Department of Pediatrics, Vagelos College of Physicians and Surgeons, Columbia University, New York, NY, USA
Michelle H. Larsen Department of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, NY, USA
W. Ian Lipkin Center for Infection and Immunity, Mailman School of Public Health, Columbia University, New York, NY, USA Department of Pathology and Cell Biology, Vagelos College of Physicians and Surgeons, Columbia University, New York, NY, USA Department of Epidemiology, Mailman School of Public Health, Columbia University, New York, NY, USA
Julius J. Lutwama Department of Arbovirology, Emerging and Re-emerging Infectious Diseases, Uganda Virus Research Institute, Entebbe, Uganda
Max R. O’Donnell Division of Pulmonary, Allergy, and Critical Care Medicine, Department of Medicine, Vagelos College of Physicians and Surgeons, Columbia University, New York, NY, USA Center for Infection and Immunity, Mailman School of Public Health, Columbia University, New York, NY, USA Department of Epidemiology, Mailman School of Public Health, Columbia University, New York, NY, USA

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Perkins MV, Joseph S, Dittmer DP, Mackman N. Cardiovascular Disease and Thrombosis in HIV Infection. Arterioscler Thromb Vasc Biol 2023;43:175-191. [PMID: 36453273 PMCID: PMC10165851 DOI: 10.1161/atvbaha.122.318232] [Citation(s) in RCA: 37] [Impact Index Per Article: 18.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/17/2022] [Accepted: 11/18/2022] [Indexed: 12/03/2022]

Ouyang J, Yan J, Zhou X, Isnard S, Harypursat V, Cui H, Routy JP, Chen Y. Relevance of biomarkers indicating gut damage and microbial translocation in people living with HIV. Front Immunol 2023;14:1173956. [PMID: 37153621 PMCID: PMC10160480 DOI: 10.3389/fimmu.2023.1173956] [Citation(s) in RCA: 11] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/25/2023] [Accepted: 04/10/2023] [Indexed: 05/10/2023] Open

Littlefield KM, Schneider JM, Neff CP, Soesanto V, Siebert JC, Nusbacher NM, Moreno-Huizar N, Cartwright IM, Armstrong AJS, Colgen SP, Lozupone CA, Palmer BE. Elevated inflammatory fecal immune factors in men who have sex with men with HIV associate with microbiome composition and gut barrier function. Front Immunol 2022;13:1072720. [PMID: 36605218 PMCID: PMC9808389 DOI: 10.3389/fimmu.2022.1072720] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/17/2022] [Accepted: 11/30/2022] [Indexed: 12/24/2022] Open

Abstract

Introduction

People living with HIV infection (PLWH) exhibit elevated levels of gastrointestinal inflammation. Potential causes of this inflammation include HIV infection and associated immune dysfunction, sexual behaviors among men who have sex with men (MSM) and gut microbiome composition.

Methods

To better understand the etiology of gastrointestinal inflammation we examined levels of 28 fecal soluble immune factors (sIFs) and the fecal microbiome in well-defined cohorts of HIV seronegative MSM (MSM-SN), MSM with untreated HIV infection (MSM-HIV) and MSM with HIV on anti-retroviral treatment (MSMART). Additionally, fecal solutes from these participants were used to stimulate T-84 colonic epithelial cells to assess barrier function.

Results

Both MSM cohorts with HIV had elevated levels of fecal calprotectin, a clinically relevant marker of GI inflammation, and nine inflammatory fecal sIFs (GM-CSF, ICAM-1, IL-1β, IL-12/23, IL-15, IL-16, TNF-β, VCAM-1, and VEGF). Interestingly, four sIFs (GM-CSF, ICAM-1, IL-7 and IL-12/23) were significantly elevated in MSM-SN compared to seronegative male non-MSM. Conversely, IL-22 and IL-13, cytokines beneficial to gut health, were decreased in all MSM with HIV and MSM-SN respectively. Importantly, all of these sIFs significantly correlated with calprotectin, suggesting they play a role in GI inflammation. Principal coordinate analysis revealed clustering of fecal sIFs by MSM status and significant associations with microbiome composition. Additionally, fecal solutes from participants in the MSM-HIV cohort significantly decreased colonic transcellular fluid transport in vitro, compared to non-MSM-SN, and this decrease associated with overall sIF composition and increased concentrations of eight inflammatory sIFs in participants with HIV. Lastly, elevated levels of plasma, sCD14 and sCD163, directly correlated with decreased transcellular transport and microbiome composition respectively, indicating that sIFs and the gut microbiome are associated with, and potentially contribute to, bacterial translocation.

Conclusion

Taken together, these data demonstrate that inflammatory sIFs are elevated in MSM, regardless of HIV infection status, and are associated with the gut microbiome and intestinal barrier function.

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Mboumba Bouassa RS, Needham J, Nohynek D, Singer J, Lee T, Bobeuf F, Samarani S, Del Balso L, Paisible N, Vertzagias C, Sebastiani G, Margolese S, Mandarino E, Klein M, Lebouché B, Cox J, Brouillette MJ, Routy JP, Szabo J, Thomas R, Huchet E, Vigano A, Jenabian MA, Costiniuk CT. Safety and Tolerability of Oral Cannabinoids in People Living with HIV on Long-Term ART: A Randomized, Open-Label, Interventional Pilot Clinical Trial (CTNPT 028). Biomedicines 2022;10:biomedicines10123168. [PMID: 36551926 PMCID: PMC9775551 DOI: 10.3390/biomedicines10123168] [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: 10/31/2022] [Revised: 11/22/2022] [Accepted: 11/24/2022] [Indexed: 12/13/2022] Open

Affiliation(s)

Ralph-Sydney Mboumba Bouassa Department of Biological Sciences and CERMO-FC Research Centre, Université du Québec à Montréal, Montreal, QC H2X 3Y7, Canada Infectious Diseases and Immunity in Global Health Program, Research Institute of McGill University Health Centre, Montreal, QC H4A 3J1, Canada
Judy Needham CIHR Canadian HIV Trials Network, Vancouver, BC V6Z 1Y6, Canada Centre for Health Evaluation and Outcome Sciences, St. Paul’s Hospital, Vancouver, BC V6Z 1Y6, Canada
Dana Nohynek CIHR Canadian HIV Trials Network, Vancouver, BC V6Z 1Y6, Canada Centre for Health Evaluation and Outcome Sciences, St. Paul’s Hospital, Vancouver, BC V6Z 1Y6, Canada
Joel Singer CIHR Canadian HIV Trials Network, Vancouver, BC V6Z 1Y6, Canada Centre for Health Evaluation and Outcome Sciences, St. Paul’s Hospital, Vancouver, BC V6Z 1Y6, Canada School of Population and Public Health, University of British Columbia, Vancouver, BC V6T 1Z4, Canada
Terry Lee CIHR Canadian HIV Trials Network, Vancouver, BC V6Z 1Y6, Canada Centre for Health Evaluation and Outcome Sciences, St. Paul’s Hospital, Vancouver, BC V6Z 1Y6, Canada
Florian Bobeuf Department of Medicine, Division of Infectious Diseases and Chronic Viral Illnesses Service, McGill University Health Centre, Montreal, QC H4A 3J1, Canada
Suzanne Samarani Infectious Diseases and Immunity in Global Health Program, Research Institute of McGill University Health Centre, Montreal, QC H4A 3J1, Canada Department of Medicine, Division of Infectious Diseases and Chronic Viral Illnesses Service, McGill University Health Centre, Montreal, QC H4A 3J1, Canada
Lina Del Balso Department of Medicine, Division of Infectious Diseases and Chronic Viral Illnesses Service, McGill University Health Centre, Montreal, QC H4A 3J1, Canada
Natalie Paisible Department of Medicine, Division of Infectious Diseases and Chronic Viral Illnesses Service, McGill University Health Centre, Montreal, QC H4A 3J1, Canada
Claude Vertzagias Department of Medicine, Division of Infectious Diseases and Chronic Viral Illnesses Service, McGill University Health Centre, Montreal, QC H4A 3J1, Canada
Giada Sebastiani Infectious Diseases and Immunity in Global Health Program, Research Institute of McGill University Health Centre, Montreal, QC H4A 3J1, Canada Department of Medicine, Division of Infectious Diseases and Chronic Viral Illnesses Service, McGill University Health Centre, Montreal, QC H4A 3J1, Canada Department of Medicine, Division of Gastroenterology and Hepatology, McGill University Health Centre, Montreal, QC H4A 3J1, Canada
Shari Margolese CIHR Canadian HIV Trials Network, Vancouver, BC V6Z 1Y6, Canada
Enrico Mandarino CIHR Canadian HIV Trials Network, Vancouver, BC V6Z 1Y6, Canada
Marina Klein Infectious Diseases and Immunity in Global Health Program, Research Institute of McGill University Health Centre, Montreal, QC H4A 3J1, Canada Department of Medicine, Division of Infectious Diseases and Chronic Viral Illnesses Service, McGill University Health Centre, Montreal, QC H4A 3J1, Canada
Bertrand Lebouché Infectious Diseases and Immunity in Global Health Program, Research Institute of McGill University Health Centre, Montreal, QC H4A 3J1, Canada Department of Medicine, Division of Infectious Diseases and Chronic Viral Illnesses Service, McGill University Health Centre, Montreal, QC H4A 3J1, Canada Department of Family Medicine, McGill University Health Centre, Montreal, QC H4A 3J1, Canada Canadian Institutes of Health Research Strategy for Patient-Oriented Research Mentorship Chair in Innovative Clinical Trials, Montreal, QC H4A 3J1, Canada
Joseph Cox Infectious Diseases and Immunity in Global Health Program, Research Institute of McGill University Health Centre, Montreal, QC H4A 3J1, Canada Department of Medicine, Division of Infectious Diseases and Chronic Viral Illnesses Service, McGill University Health Centre, Montreal, QC H4A 3J1, Canada
Marie-Josée Brouillette Infectious Diseases and Immunity in Global Health Program, Research Institute of McGill University Health Centre, Montreal, QC H4A 3J1, Canada Department of Medicine, Division of Infectious Diseases and Chronic Viral Illnesses Service, McGill University Health Centre, Montreal, QC H4A 3J1, Canada Department of Psychiatry, McGill University Health Centre, Montreal, QC H4A 3J1, Canada
Jean-Pierre Routy Infectious Diseases and Immunity in Global Health Program, Research Institute of McGill University Health Centre, Montreal, QC H4A 3J1, Canada Department of Medicine, Division of Infectious Diseases and Chronic Viral Illnesses Service, McGill University Health Centre, Montreal, QC H4A 3J1, Canada Department of Medicine, Division of Hematology, McGill University Health Centre, Montreal, QC H4A 3J1, Canada
Jason Szabo Department of Medicine, Division of Infectious Diseases and Chronic Viral Illnesses Service, McGill University Health Centre, Montreal, QC H4A 3J1, Canada Department of Family Medicine, McGill University Health Centre, Montreal, QC H4A 3J1, Canada Clinique Médical L’Actuel, Montreal, QC H2L 4P9, Canada
Réjean Thomas Clinique Médical L’Actuel, Montreal, QC H2L 4P9, Canada
Emmanuel Huchet Clinique Médical L’Agora, Montreal, QC H2L 4E9, Canada
Antonio Vigano Medical Cannabis Program in Oncology, Cedars Cancer Center, McGill University Health Centre, 1001 Boulevard Decarie, Montreal, QC H4A 3J1, Canada Centre for Cannabis Research, McGill University, Montreal, QC H3A 0G4, Canada
Mohammad-Ali Jenabian Department of Biological Sciences and CERMO-FC Research Centre, Université du Québec à Montréal, Montreal, QC H2X 3Y7, Canada Department of Microbiology, Infectiology and Immunology, Université de Montréal, Montreal, QC H3T 1J4, Canada
Cecilia T Costiniuk Infectious Diseases and Immunity in Global Health Program, Research Institute of McGill University Health Centre, Montreal, QC H4A 3J1, Canada Department of Medicine, Division of Infectious Diseases and Chronic Viral Illnesses Service, McGill University Health Centre, Montreal, QC H4A 3J1, Canada Centre for Cannabis Research, McGill University, Montreal, QC H3A 0G4, Canada Department of Microbiology and Immunology, McGill University, Montreal, QC H3A 0G4, Canada Correspondence: ; Tel.: +1-514-934-1934 (ext. 76195); Fax: +1-514-843-2209

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Madzime M, Theron AJ, Anderson R, Tintinger GR, Steel HC, Meyer PWA, Nel JG, Feldman C, Rossouw TM. Dolutegravir potentiates platelet activation by a calcium-dependent, ionophore-like mechanism. J Immunotoxicol 2022;19:1-8. [PMID: 36394569 DOI: 10.1080/1547691x.2022.2142705] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/18/2022] Open

Abstract

Dolutegravir is a highly potent HIV integrase strand transfer inhibitor that is recommended for first-line anti-retroviral treatment in all major treatment guidelines. A recent study has shown that people taking this class of anti-retroviral treatment have a substantially higher risk of early-onset cardiovascular disease, a condition shown previously to be associated with increased platelet reactivity. To date, few studies have explored the effects of dolutegravir on platelet activation. Accordingly, the current study was undertaken with the primary objective of investigating the effects of dolutegravir on the reactivity of human platelets in vitro. Platelet-rich plasma, isolated platelets, or buffy coat cell suspensions prepared from the blood of healthy adults were treated with dolutegravir (2.5-10 µg/ml), followed by activation with adenosine 5'-diphosphate (ADP), thrombin, or a thromboxane A₂ receptor agonist U46619. Expression of platelet CD62P (P-selectin), formation of heterotypic neutrophil:platelet aggregates, and calcium (Ca²⁺) fluxes were measured using flow cytometry and fluorescence spectrometry, respectively. Dolutegravir caused dose-related potentiation of ADP-, thrombin- and U46619-activated expression of CD62P by platelets, as well as a significant increases in formation of neutrophil:platelet aggregates. These effects were paralleled by a spontaneous, receptor-independent elevation in cytosolic Ca²⁺ that appears to underpin the mechanism by which the antiretroviral agent augments the responsiveness of these cells to ADP, thrombin and U46619. The most likely mechanism of dolutegravir-mediated increases in platelet cytosolic Ca²⁺ relates to a combination of lipophilicity and divalent/trivalent metal-binding and/or chelating properties of the anti-retroviral agent. These properties are likely to confer ionophore-type activities on dolutegravir that would promote movement of Ca²⁺ across the plasma membrane, delivering the cation to the cytosol where it would augment Ca²⁺-dependent intracellular signaling mechanisms. These effects of dolutegravir may lead to hyper-activation of platelets which, if operative in vivo, may contribute to an increased risk for cardiometabolic co-morbidities.

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Xiao Q, Yu F, Yan L, Zhao H, Zhang F. Alterations in circulating markers in HIV/AIDS patients with poor immune reconstitution: Novel insights from microbial translocation and innate immunity. Front Immunol 2022;13:1026070. [PMID: 36325329 PMCID: PMC9618587 DOI: 10.3389/fimmu.2022.1026070] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/23/2022] [Accepted: 09/29/2022] [Indexed: 11/13/2022] Open

Schapkaitz E, Jacobson BF, Libhaber E. Pregnancy Related Venous Thromboembolism-Associated with HIV Infection and Antiretroviral Therapy. Semin Thromb Hemost 2022;49:355-363. [PMID: 36055274 DOI: 10.1055/s-0042-1754391] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/14/2022]

The Role of Immunometabolism in HIV-1 Pathogenicity: Links to Immune Cell Responses. Viruses 2022;14:v14081813. [PMID: 36016435 PMCID: PMC9415820 DOI: 10.3390/v14081813] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/15/2022] [Revised: 08/11/2022] [Accepted: 08/15/2022] [Indexed: 11/17/2022] Open

Schapkaitz E, Libhaber E, Jacobson BF, Toman M, Gerber A, Büller HR. Evaluation of markers of fibrinolysis and coagulation in pregnant women with human immunodeficiency virus. Thromb Res 2022;217:1-8. [PMID: 35810616 DOI: 10.1016/j.thromres.2022.07.001] [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: 02/20/2022] [Revised: 05/31/2022] [Accepted: 07/04/2022] [Indexed: 11/30/2022]

Immunometabolic Reprogramming in Response to HIV Infection Is Not Fully Normalized by Suppressive Antiretroviral Therapy. Viruses 2022;14:v14061313. [PMID: 35746785 PMCID: PMC9228482 DOI: 10.3390/v14061313] [Citation(s) in RCA: 13] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/28/2022] [Revised: 06/07/2022] [Accepted: 06/09/2022] [Indexed: 11/25/2022] Open

Geng ST, Zhang JB, Wang YX, Xu Y, Lu D, Zhang Z, Gao J, Wang KH, Kuang YQ. Pre-Digested Protein Enteral Nutritional Supplementation Enhances Recovery of CD4⁺ T Cells and Repair of Intestinal Barrier in HIV-Infected Immunological Non-Responders. Front Immunol 2022;12:757935. [PMID: 35003070 PMCID: PMC8741150 DOI: 10.3389/fimmu.2021.757935] [Citation(s) in RCA: 10] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/13/2021] [Accepted: 12/13/2021] [Indexed: 12/12/2022] Open

Affiliation(s)

Shi-Tao Geng National Health Commission (NHC) Key Laboratory of Drug Addiction Medicine, First Affiliated Hospital of Kunming Medical University, Kunming Medical University, Kunming, China.,Scientific Research Laboratory Center, First Affiliated Hospital of Kunming Medical University, Kunming, China.,Department of Gastrointestinal and Hernia Surgery, First Affiliated Hospital of Kunming Medical University, Kunming, China
Jian-Bo Zhang Department of Dermatology, Second People's Hospital of Dali City, Dali, China
Yue-Xin Wang National Health Commission (NHC) Key Laboratory of Drug Addiction Medicine, First Affiliated Hospital of Kunming Medical University, Kunming Medical University, Kunming, China.,Scientific Research Laboratory Center, First Affiliated Hospital of Kunming Medical University, Kunming, China.,Department of Gastrointestinal and Hernia Surgery, First Affiliated Hospital of Kunming Medical University, Kunming, China
Yu Xu National Health Commission (NHC) Key Laboratory of Drug Addiction Medicine, First Affiliated Hospital of Kunming Medical University, Kunming Medical University, Kunming, China.,Scientific Research Laboratory Center, First Affiliated Hospital of Kunming Medical University, Kunming, China
Danfeng Lu National Health Commission (NHC) Key Laboratory of Drug Addiction Medicine, First Affiliated Hospital of Kunming Medical University, Kunming Medical University, Kunming, China.,Scientific Research Laboratory Center, First Affiliated Hospital of Kunming Medical University, Kunming, China
Zunyue Zhang National Health Commission (NHC) Key Laboratory of Drug Addiction Medicine, First Affiliated Hospital of Kunming Medical University, Kunming Medical University, Kunming, China.,Scientific Research Laboratory Center, First Affiliated Hospital of Kunming Medical University, Kunming, China
Ju Gao Department of Dermatology, Second People's Hospital of Dali City, Dali, China
Kun-Hua Wang National Health Commission (NHC) Key Laboratory of Drug Addiction Medicine, First Affiliated Hospital of Kunming Medical University, Kunming Medical University, Kunming, China.,Department of Gastrointestinal and Hernia Surgery, First Affiliated Hospital of Kunming Medical University, Kunming, China.,School of Medicine, Yunnan University, Kunming, China
Yi-Qun Kuang National Health Commission (NHC) Key Laboratory of Drug Addiction Medicine, First Affiliated Hospital of Kunming Medical University, Kunming Medical University, Kunming, China.,Scientific Research Laboratory Center, First Affiliated Hospital of Kunming Medical University, Kunming, China

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Crespo-Bermejo C, de Arellano ER, Lara-Aguilar V, Valle-Millares D, Gómez-Lus ML, Madrid R, Martín-Carbonero L, Briz V. Persistent low-Level viremia in persons living with HIV undertreatment: An unresolved status. Virulence 2021;12:2919-2931. [PMID: 34874239 PMCID: PMC8654475 DOI: 10.1080/21505594.2021.2004743] [Citation(s) in RCA: 36] [Impact Index Per Article: 9.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022] Open

Asowata OE, Singh A, Ngoepe A, Herbert N, Fardoos R, Reddy K, Zungu Y, Nene F, Mthabela N, Ramjit D, Karim F, Govender K, Ndung'u T, Porterfield JZ, Adamson JH, Madela FG, Manzini VT, Anderson F, Leslie A, Kløverpris HN. Irreversible depletion of intestinal CD4+ T cells is associated with T cell activation during chronic HIV infection. JCI Insight 2021;6:146162. [PMID: 34618690 PMCID: PMC8663780 DOI: 10.1172/jci.insight.146162] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/17/2020] [Accepted: 10/06/2021] [Indexed: 01/04/2023] Open

Affiliation(s)

Osaretin E Asowata Africa Health Research Institute (AHRI), Durban, South Africa.,School of Laboratory Medicine and Medical Sciences, University of KwaZulu-Natal, Durban, South Africa
Alveera Singh Africa Health Research Institute (AHRI), Durban, South Africa
Abigail Ngoepe Africa Health Research Institute (AHRI), Durban, South Africa
Nicholas Herbert Africa Health Research Institute (AHRI), Durban, South Africa
Rabiah Fardoos Africa Health Research Institute (AHRI), Durban, South Africa.,Department of Immunology and Microbiology, University of Copenhagen, Denmark
Kavidha Reddy Africa Health Research Institute (AHRI), Durban, South Africa
Yenzekile Zungu Africa Health Research Institute (AHRI), Durban, South Africa
Faith Nene Africa Health Research Institute (AHRI), Durban, South Africa
Ntombifuthi Mthabela Africa Health Research Institute (AHRI), Durban, South Africa
Dirhona Ramjit Africa Health Research Institute (AHRI), Durban, South Africa
Farina Karim Africa Health Research Institute (AHRI), Durban, South Africa
Katya Govender Africa Health Research Institute (AHRI), Durban, South Africa
Thumbi Ndung'u Africa Health Research Institute (AHRI), Durban, South Africa.,School of Laboratory Medicine and Medical Sciences, University of KwaZulu-Natal, Durban, South Africa.,University College London, Division of Infection and Immunity, London, United Kingdom.,Max Planck Institute for Infection Biology, Berlin, Germany
J Zachary Porterfield Africa Health Research Institute (AHRI), Durban, South Africa.,Department of Microbiology, Immunology, and Molecular Genetics, University of Kentucky, Lexington, Kentucky, USA
John H Adamson Africa Health Research Institute (AHRI), Durban, South Africa
Fusi G Madela Division Upper Gastrointestinal Tract and Colorectal Surgery, Inkosi Albert Luthuli Central Hospital (IALCH), University of KwaZulu-Natal, Durban, South Africa
Vukani T Manzini Division Upper Gastrointestinal Tract and Colorectal Surgery, Inkosi Albert Luthuli Central Hospital (IALCH), University of KwaZulu-Natal, Durban, South Africa
Frank Anderson Division Upper Gastrointestinal Tract and Colorectal Surgery, Inkosi Albert Luthuli Central Hospital (IALCH), University of KwaZulu-Natal, Durban, South Africa
Alasdair Leslie Africa Health Research Institute (AHRI), Durban, South Africa.,School of Laboratory Medicine and Medical Sciences, University of KwaZulu-Natal, Durban, South Africa.,University College London, Division of Infection and Immunity, London, United Kingdom
Henrik N Kløverpris Africa Health Research Institute (AHRI), Durban, South Africa.,School of Laboratory Medicine and Medical Sciences, University of KwaZulu-Natal, Durban, South Africa.,Department of Immunology and Microbiology, University of Copenhagen, Denmark.,University College London, Division of Infection and Immunity, London, United Kingdom

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Ishizaka A, Koga M, Mizutani T, Parbie PK, Prawisuda D, Yusa N, Sedohara A, Kikuchi T, Ikeuchi K, Adachi E, Koibuchi T, Furukawa Y, Tojo A, Imoto S, Suzuki Y, Tsutsumi T, Kiyono H, Matano T, Yotsuyanagi H. Unique Gut Microbiome in HIV Patients on Antiretroviral Therapy (ART) Suggests Association with Chronic Inflammation. Microbiol Spectr 2021;9:e0070821. [PMID: 34378948 PMCID: PMC8552706 DOI: 10.1128/spectrum.00708-21] [Citation(s) in RCA: 56] [Impact Index Per Article: 14.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/11/2021] [Accepted: 07/13/2021] [Indexed: 02/07/2023] Open

Abstract

Chronic inflammation is a hallmark of human immunodeficiency virus (HIV) infection and a risk factor for the development and progression of age-related comorbidities. Although HIV-associated gut dysbiosis has been suggested to be involved in sustained chronic inflammation, there remains a limited understanding of the association between gut dysbiosis and chronic inflammation during HIV infection. Here, we investigated compositional changes in the gut microbiome and its role in chronic inflammation in patients infected with HIV. We observed that the gut microbiomes of patients with low CD4 counts had reduced alpha diversity compared to those in uninfected controls. Following CD4 recovery, alpha diversity was restored, but intergroup dissimilarity of bacterial composition remained unchanged between patients and uninfected controls. Patients with HIV had higher abundance of the classes Negativicutes, Bacilli, and Coriobacteriia, as well as depletion of the class Clostridia. These relative abundances positively correlated with inflammatory cytokines and negatively correlated with anti-inflammatory cytokines. We found that gut dysbiosis accompanying HIV infection was characterized by a depletion of obligate anaerobic Clostridia and enrichment of facultative anaerobic bacteria, reflecting increased intestinal oxygen levels and intestinal permeability. Furthermore, it is likely that HIV-associated dysbiosis shifts the immunological balance toward inflammatory Th1 responses and encourages proinflammatory cytokine production. Our results suggest that gut dysbiosis contributes to sustaining chronic inflammation in patients with HIV infection despite effective antiretroviral therapy and that correcting gut dysbiosis will be effective in improving long-term outcomes in patients. IMPORTANCE Chronic inflammation is a hallmark of HIV infection and is associated with the development and progression of age-related comorbidities. Although the gastrointestinal tract is a major site of HIV replication and CD4+ T-cell depletion, the role of HIV-associated imbalance of gut microbiome in chronic inflammation is unclear. Here, we aimed to understand the causal relationship between abnormalities in the gut microbiome and chronic inflammation in patients with HIV. Our results suggest HIV-associated gut dysbiosis presents a more aerobic environment than that of healthy individuals, despite prolonged viral suppression. This dysbiosis likely results from a sustained increase in intestinal permeability, which supports sustained bacterial translocation in HIV patients, despite effective therapy. Additionally, we observed that several bacterial taxa enriched in HIV patients were associated with increased expression of inflammatory cytokines. Collectively, these results suggest that gut dysbiosis plays an important role in chronic inflammation in HIV patients.

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Affiliation(s)

Aya Ishizaka Division of Infectious Diseases, Advanced Clinical Research Center, the Institute of Medical Science, The University of Tokyo, Tokyo, Japan International Research and Development Center for Mucosal Vaccines, the Institute of Medical Science, The University of Tokyo, Tokyo, Japan
Michiko Koga Division of Infectious Diseases, Advanced Clinical Research Center, the Institute of Medical Science, The University of Tokyo, Tokyo, Japan
Taketoshi Mizutani Division of Infectious Diseases, Advanced Clinical Research Center, the Institute of Medical Science, The University of Tokyo, Tokyo, Japan International Research and Development Center for Mucosal Vaccines, the Institute of Medical Science, The University of Tokyo, Tokyo, Japan
Prince Kofi Parbie AIDS Research Center, National Institute of Infectious Diseases, Tokyo, Japan
Diki Prawisuda Division of Infectious Diseases, Advanced Clinical Research Center, the Institute of Medical Science, The University of Tokyo, Tokyo, Japan
Nozomi Yusa Department of Applied Genomics, Research Hospital, Institute of Medical Science, The University of Tokyo, Tokyo, Japan
Ayako Sedohara Division of Infectious Diseases, Advanced Clinical Research Center, the Institute of Medical Science, The University of Tokyo, Tokyo, Japan
Tadashi Kikuchi AIDS Research Center, National Institute of Infectious Diseases, Tokyo, Japan Department of Infectious Diseases and Applied Immunology, IMSUT Hospital of Institute of Medical Science, The University of Tokyo, Tokyo, Japan
Kazuhiko Ikeuchi Department of Infectious Diseases and Applied Immunology, IMSUT Hospital of Institute of Medical Science, The University of Tokyo, Tokyo, Japan
Eisuke Adachi Department of Infectious Diseases and Applied Immunology, IMSUT Hospital of Institute of Medical Science, The University of Tokyo, Tokyo, Japan
Tomohiko Koibuchi Department of Infectious Diseases and Applied Immunology, IMSUT Hospital of Institute of Medical Science, The University of Tokyo, Tokyo, Japan
Yoichi Furukawa Department of Applied Genomics, Research Hospital, Institute of Medical Science, The University of Tokyo, Tokyo, Japan
Arinobu Tojo Department of Laboratory Medicine, Research Hospital, Institute of Medical Science, The University of Tokyo, Tokyo, Japan
Seiya Imoto Division of Health Medical Data Science, Health Intelligence Center, the Institute of Medical Science, The University of Tokyo, Tokyo, Japan
Yutaka Suzuki Department of Computational Biology and Medical Sciences, Graduate School of Frontier Sciences, The University of Tokyo, Chiba, Japan
Takeya Tsutsumi Division of Infectious Diseases, Advanced Clinical Research Center, the Institute of Medical Science, The University of Tokyo, Tokyo, Japan
Hiroshi Kiyono International Research and Development Center for Mucosal Vaccines, the Institute of Medical Science, The University of Tokyo, Tokyo, Japan
Tetsuro Matano AIDS Research Center, National Institute of Infectious Diseases, Tokyo, Japan Department of AIDS Vaccine Development, IMSUT Hospital, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan
Hiroshi Yotsuyanagi Division of Infectious Diseases, Advanced Clinical Research Center, the Institute of Medical Science, The University of Tokyo, Tokyo, Japan Department of Infectious Diseases and Applied Immunology, IMSUT Hospital of Institute of Medical Science, The University of Tokyo, Tokyo, Japan

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Tanes C, Walker EM, Slisarenko N, Gerrets GL, Grasperge BF, Qin X, Jazwinski SM, Bushman FD, Bittinger K, Rout N. Gut Microbiome Changes Associated with Epithelial Barrier Damage and Systemic Inflammation during Antiretroviral Therapy of Chronic SIV Infection. Viruses 2021;13:1567. [PMID: 34452432 PMCID: PMC8402875 DOI: 10.3390/v13081567] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/28/2021] [Revised: 08/01/2021] [Accepted: 08/05/2021] [Indexed: 12/26/2022] Open

HIV is associated with an increased risk of age-related clonal hematopoiesis among older adults. Nat Med 2021;27:1006-1011. [PMID: 34099923 DOI: 10.1038/s41591-021-01357-y] [Citation(s) in RCA: 63] [Impact Index Per Article: 15.8] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/11/2020] [Accepted: 04/19/2021] [Indexed: 12/13/2022]

Siedner MJ, Bibangambah P, Kim J, Lankowski A, Chang JL, Yang IT, Kwon DS, North CM, Triant VA, Longenecker C, Ghoshhajra B, Peck RN, Sentongo RN, Gilbert R, Kakuhikire B, Boum Y, Haberer JE, Martin JN, Tracy R, Hunt PW, Bangsberg DR, Tsai AC, Hemphill LC, Okello S. Treated HIV Infection and Progression of Carotid Atherosclerosis in Rural Uganda: A Prospective Observational Cohort Study. J Am Heart Assoc 2021;10:e019994. [PMID: 34096320 PMCID: PMC8477876 DOI: 10.1161/jaha.120.019994] [Citation(s) in RCA: 14] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]

Abstract

Background Although ≈70% of the world's population of people living with HIV reside in sub-Saharan Africa, there are minimal prospective data on the contributions of HIV infection to atherosclerosis in the region. Methods and Results We conducted a prospective observational cohort study of people living with HIV on antiretroviral therapy >40 years of age in rural Uganda, along with population-based comparators not infected with HIV. We collected data on cardiovascular disease risk factors and carotid ultrasound measurements annually. We fitted linear mixed effects models, adjusted for cardiovascular disease risk factors, to estimate the association between HIV serostatus and progression of carotid intima media thickness (cIMT). We enrolled 155 people living with HIV and 154 individuals not infected with HIV and collected cIMT images at 1045 visits during a median of 4 annual visits per participant (interquartile range 3-4, range 1-5). Age (median 50.9 years) and sex (49% female) were similar by HIV serostatus. At enrollment, there was no difference in mean cIMT by HIV serostatus (0.665 versus 0.680 mm, P=0.15). In multivariable models, increasing age, blood pressure, and non-high-density lipoprotein cholesterol were associated with greater cIMT (P<0.05), however change in cIMT per year was also no different by HIV serostatus (0.004 mm/year for HIV negative [95% CI, 0.001-0.007 mm], 0.006 mm/year for people living with HIV [95% CI, 0.003-0.008 mm], HIV×time interaction P=0.25). Conclusions In rural Uganda, treated HIV infection was not associated with faster cIMT progression. These results do not support classification of treated HIV infection as a risk factor for subclinical atherosclerosis progression in rural sub-Saharan Africa. Registration URL: https://www.ClinicalTrials.gov; Unique identifier: NCT02445079.

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Affiliation(s)

Mark J. Siedner Department of MedicineHarvard Medical SchoolBostonMA,Departments of Medicine and PsychiatryMassachusetts General HospitalBostonMA,Faculty of MedicineMbarara University of Science and TechnologyMbararaUganda
Prossy Bibangambah Faculty of MedicineMbarara University of Science and TechnologyMbararaUganda
June‐Ho Kim Department of MedicineHarvard Medical SchoolBostonMA,Department of MedicineBrigham and Women's HospitalBostonMA
Alexander Lankowski Department of MedicineUniversity of WashingtonSeattleWA,Vaccine and Infectious Disease DivisionFred Hutchinson Cancer Research CenterSeattleWA
Jonathan L. Chang Department of MedicineHarvard Medical SchoolBostonMA,Department of MedicineBrigham and Women's HospitalBostonMA
Isabelle T. Yang Department of MedicineGeisel School of Medicine at DartmouthHanoverNH
Douglas S. Kwon Department of MedicineHarvard Medical SchoolBostonMA,Departments of Medicine and PsychiatryMassachusetts General HospitalBostonMA,Ragon Institute of Massachusetts General Hospital, Massachusetts Institute of Technology, and HarvardCambridgeMA
Crystal M. North Department of MedicineHarvard Medical SchoolBostonMA,Departments of Medicine and PsychiatryMassachusetts General HospitalBostonMA
Virginia A. Triant Department of MedicineHarvard Medical SchoolBostonMA,Departments of Medicine and PsychiatryMassachusetts General HospitalBostonMA
Christopher Longenecker Department of MedicineCase Western Reserve UniversityClevelandOH
Brian Ghoshhajra Department of MedicineHarvard Medical SchoolBostonMA,Departments of Medicine and PsychiatryMassachusetts General HospitalBostonMA
Robert N. Peck Center for Global HealthWeill Cornell Medical CollegeNew YorkNY
Ruth N. Sentongo Faculty of MedicineMbarara University of Science and TechnologyMbararaUganda
Rebecca Gilbert Departments of Medicine and PsychiatryMassachusetts General HospitalBostonMA
Bernard Kakuhikire Faculty of MedicineMbarara University of Science and TechnologyMbararaUganda
Yap Boum Epicentre Research BaseMbararaUganda
Jessica E. Haberer Department of MedicineHarvard Medical SchoolBostonMA,Departments of Medicine and PsychiatryMassachusetts General HospitalBostonMA
Jeffrey N. Martin Department of MedicineUniversity of CaliforniaSan FranciscoCA
Russell Tracy Department of Pathology and Laboratory MedicineUniversity of VermontBurlingtonVT
Peter W. Hunt Department of MedicineUniversity of CaliforniaSan FranciscoCA
David R. Bangsberg School of Public HealthOregon Health Sciences UniversityPortlandOR
Alexander C. Tsai Department of MedicineHarvard Medical SchoolBostonMA,Departments of Medicine and PsychiatryMassachusetts General HospitalBostonMA,Faculty of MedicineMbarara University of Science and TechnologyMbararaUganda
Linda C. Hemphill Department of MedicineHarvard Medical SchoolBostonMA,Departments of Medicine and PsychiatryMassachusetts General HospitalBostonMA
Samson Okello Faculty of MedicineMbarara University of Science and TechnologyMbararaUganda

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Probiotics to manage inflammation in HIV infection. Curr Opin Infect Dis 2021;33:34-43. [PMID: 31789692 DOI: 10.1097/qco.0000000000000612] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]

Walker EM, Slisarenko N, Gerrets GL, Grasperge BF, Mattison JA, Kissinger PJ, Welsh DA, Veazey RS, Jazwinski SM, Rout N. Dysregulation of IL-17/IL-22 Effector Functions in Blood and Gut Mucosal Gamma Delta T Cells Correlates With Increase in Circulating Leaky Gut and Inflammatory Markers During cART-Treated Chronic SIV Infection in Macaques. Front Immunol 2021;12:647398. [PMID: 33717202 PMCID: PMC7946846 DOI: 10.3389/fimmu.2021.647398] [Citation(s) in RCA: 14] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/29/2020] [Accepted: 01/21/2021] [Indexed: 12/18/2022] Open

Abstract

HIV-associated inflammation has been implicated in the premature aging and increased risk of age-associated comorbidities in cART-treated individuals. However, the immune mechanisms underlying the chronic inflammatory state of cART-suppressed HIV infection remain unclear. Here, we investigated the role of γδT cells, a group of innate IL-17 producing T lymphocytes, in the development of systemic inflammation and leaky gut phenotype during cART-suppressed SIV infection of macaques. Plasma levels of inflammatory mediators, intestinal epithelial barrier disruption (IEBD) and microbial translocation (MT) biomarkers, and Th1/Th17-type cytokine functions were longitudinally assessed in blood and gut mucosa of SIV-infected, cART-suppressed macaques. Among the various gut mucosal IL-17/IL-22-producing T lymphocyte subsets including Th17, γδT, CD161+ CD8+ T, and MAIT cells, a specific decline in the Vδ2 subset of γδT cells and impaired IL-17/IL-22 production in γδT cells significantly correlated with the subsequent increase in plasma IEBD/MT markers (IFABP, LPS-binding protein, and sCD14) and pro-inflammatory cytokines (IL-6, IL-1β, IP10, etc.) despite continued viral suppression during long-term cART. Further, the plasma inflammatory cytokine signature during long-term cART was distinct from acute SIV infection and resembled the inflammatory cytokine profile of uninfected aging (inflammaging) macaques. Overall, our data suggest that during cART-suppressed chronic SIV infection, dysregulation of IL-17/IL-22 cytokine effector functions and decline of Vδ2 γδT cell subsets may contribute to gut epithelial barrier disruption and development of a distinct plasma inflammatory signature characteristic of inflammaging. Our results advance the current understanding of the impact of chronic HIV/SIV infection on γδT cell functions and demonstrate that in the setting of long-term cART, the loss of epithelial barrier-protective functions of Vδ2 T cells and ensuing IEBD/MT occurs before the hallmark expansion of Vδ1 subsets and skewed Vδ2/Vδ1 ratio. Thus, our work suggests that novel therapeutic approaches toward restoring IL-17/IL-22 cytokine functions of intestinal Vδ2 T cells may be beneficial in preserving gut epithelial barrier function and reducing chronic inflammation in HIV-infected individuals.

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van Welzen BJ, Oomen PGA, Hoepelman AIM. Dual Antiretroviral Therapy-All Quiet Beneath the Surface? Front Immunol 2021;12:637910. [PMID: 33643320 PMCID: PMC7906996 DOI: 10.3389/fimmu.2021.637910] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/04/2020] [Accepted: 01/22/2021] [Indexed: 11/13/2022] Open

Teer E, Joseph DE, Glashoff RH, Faadiel Essop M. Monocyte/Macrophage-Mediated Innate Immunity in HIV-1 Infection: From Early Response to Late Dysregulation and Links to Cardiovascular Diseases Onset. Virol Sin 2021;36:565-576. [PMID: 33400091 DOI: 10.1007/s12250-020-00332-0] [Citation(s) in RCA: 20] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/29/2020] [Accepted: 10/26/2020] [Indexed: 12/11/2022] Open

Temu TM, Zifodya JS, Polyak SJ, Wagoner J, Wanjalla CN, Masyuko S, Nyabiage J, Kinuthia J, Bloomfield GS, Page ST, Farquhar C. Antiretroviral therapy reduces but does not normalize immune and vascular inflammatory markers in adults with chronic HIV infection in Kenya. AIDS 2021;35:45-51. [PMID: 33055570 PMCID: PMC7718419 DOI: 10.1097/qad.0000000000002729] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]

Abstract

INTRODUCTION

Markers of monocyte/macrophage activation and vascular inflammation are associated with HIV-related cardiovascular diseases (CVD) and mortality. We compared these markers among African people living with HIV (PLWH) and HIV-negative adults, and examined risk factors associated with elevated biomarkers (>75th percentile) in PLWH on antiretroviral therapy (ART).

DESIGN

Cross-sectional study.

METHODS

We measured serum concentrations of a gut integrity biomarker (intestinal-fatty acid binding protein), monocyte/macrophage activation biomarkers (soluble CD14 and CD163), and vascular inflammation biomarkers [soluble intercellular adhesion molecule 1 (sICAM-1) and soluble vascular adhesion molecule 1 (sVCAM-1)]. We assessed the relationship of these inflammatory parameters with HIV, using logistic regression adjusting for traditional CVD risk factors.

RESULTS

Among the 541 participants, median age was 43 years and half were female. Among 275 PLWH, median CD4 T-cell count and duration of ART use was 509 cells/μl and 8 years, respectively. PLWH had significantly higher prevalence of elevated inflammatory biomarkers compared with HIV-negative individuals even after adjustment for traditional CVD risk factors. Compared with individuals without HIV, the prevalence of elevated biomarkers was highest among persons with detectable viral load and CD4 T-cell counts 200 cells/μl or less. In a subanalysis among PLWH, nadir CD4 T-cell count 200 cells/μl or less was associated with elevated soluble CD14 (sCD14); dyslipidemia with elevated sCD14, sICAM-1, and sVCAM-1; and overweight/obesity with reduced sCD14. Longer ART exposure (>4 years) was associated with reduced sVCAM-1 and sICAM-1.

CONCLUSION

HIV and not traditional CVD risk factors is a primary contributor of monocyte/macrophage activation and inflammation despite ART. Anti-inflammatory therapies in addition to ART may be necessary to reduce these immune dysregulations and improve health outcomes of African PLWH.

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Masyuko SJ, Page ST, Polyak SJ, Kinuthia J, Osoti AO, Otieno FC, Kibachio JM, Mogaka JN, Macharia PM, Chohan BH, Wogner J, O'Connor A, Temu TM, Zifodya JS, Otedo A, Nakanjako D, Hughes JP, Farquhar C. Human Immunodeficiency Virus Is Associated With Higher Levels of Systemic Inflammation Among Kenyan Adults Despite Viral Suppression. Clin Infect Dis 2020;73:e2034-e2042. [PMID: 33313687 DOI: 10.1093/cid/ciaa1650] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/23/2020] [Indexed: 01/01/2023] Open

Abstract

BACKGROUND

Systemic inflammation independently predicts future cardiovascular events and is associated with a 2-fold increase in cardiovascular disease (CVD) risk among persons living with human immunodeficiency virus (PLHIV). We examined the association between inflammatory markers, HIV status, and traditional CVD risk factors.

METHODS

We conducted a cross-sectional study of Kenyan adults with and without HIV seeking care at Kisumu County Hospital. Using a multiplex immunoassay, we measured interleukin (IL) 1β, IL-6, tumor necrosis factor α (TNF-α), and high-sensitivity C-reactive protein (hsCRP) concentrations. We compared inflammatory marker concentrations by HIV status using the Wilcoxon rank-sum test. Multivariable linear regression was used to evaluate associations between inflammatory biomarkers and HIV status, adjusting for CVD risk factors.

RESULTS

We enrolled 286 PLHIV and 277 HIV-negative participants. Median duration of antiretroviral therapy for PLHIV was 8 years (interquartile range, 4-10) and 96% were virally suppressed. PLHIV had a 51% higher mean IL-6 concentration (P < .001), 39% higher mean IL-1β (P = .005), 40% higher mean TNF-α (P < .001), and 27% higher mean hsCRP (P = .008) compared with HIV-negative participants, independent of CVD risk factors. Male sex, older age, and obesity were associated with higher concentrations of inflammatory markers. Restricting to PLHIV, viral load of ≥1000 copies/mL was associated with higher TNF-α levels (P = .013).

CONCLUSIONS

We found higher levels of systemic inflammatory biomarkers among PLHIV who were virally suppressed, and this was independent of traditional CVD risk factors. Further longitudinal analyses to determine whether these inflammatory markers predict future CVD events, and are possible therapeutic targets among PLHIV, are warranted.

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Affiliation(s)

Sarah J Masyuko Ministry of Health, Nairobi, Kenya.,Department of Global Health, University of Washington, Seattle, Washington, USA
Stephanie T Page Department of Global Health, University of Washington, Seattle, Washington, USA.,Department of Medicine, University of Washington, Seattle, Washington, USA
Stephen J Polyak Department of Global Health, University of Washington, Seattle, Washington, USA.,Department of Laboratory Medicine and Pathology, University of Washington, Seattle, Washington, USA
John Kinuthia Department of Research and Programs, Kenyatta National Hospital, Nairobi, Kenya
Alfred O Osoti Department of Global Health, University of Washington, Seattle, Washington, USA.,Department of Obstetrics and Gynecology, University of Nairobi, Nairobi, Kenya
Fredrick C Otieno Department of Clinical Medicine and Therapeutics, College of Health Sciences, University of Nairobi, Nairobi, Kenya
Joseph M Kibachio Ministry of Health, Nairobi, Kenya
Jerusha N Mogaka Department of Medicine, University of Washington, Seattle, Washington, USA
Paul M Macharia Ministry of Health, Nairobi, Kenya
Bhavna H Chohan Department of Global Health, University of Washington, Seattle, Washington, USA
Jessica Wogner Department of Laboratory Medicine and Pathology, University of Washington, Seattle, Washington, USA
Aidan O'Connor Department of Laboratory Medicine and Pathology, University of Washington, Seattle, Washington, USA
Tecla M Temu Department of Global Health, University of Washington, Seattle, Washington, USA
Jerry S Zifodya Department of Medicine, Tulane University, New Orleans, Louisiana, USA
Amos Otedo Ministry of Health, Nairobi, Kenya
Damalie Nakanjako Department of Medicine, School of Medicine, Makerere University College of Health Sciences, Kampala, Uganda
James P Hughes Department of Biostatistics, University of Washington, Seattle, Washington, USA
Carey Farquhar Department of Global Health, University of Washington, Seattle, Washington, USA.,Department of Medicine, University of Washington, Seattle, Washington, USA.,Department of Epidemiology, University of Washington, Seattle, Washington, USA

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Bhattacharya P, Ellegård R, Khalid M, Svanberg C, Govender M, Keita ÅV, Söderholm JD, Myrelid P, Shankar EM, Nyström S, Larsson M. Complement opsonization of HIV affects primary infection of human colorectal mucosa and subsequent activation of T cells. eLife 2020;9:e57869. [PMID: 32876566 PMCID: PMC7492089 DOI: 10.7554/elife.57869] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/15/2020] [Accepted: 09/02/2020] [Indexed: 02/06/2023] Open

Kantamala D, Praparattanapan J, Taejaroenkul S, Srithep S, Yoosupap R, Supparatpinyo K. High microbial translocation limits gut immune recovery during short-term HAART in the area with high prevalence of foodborne infection. Cytokine 2020;136:155257. [PMID: 32861144 DOI: 10.1016/j.cyto.2020.155257] [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: 05/19/2020] [Revised: 08/07/2020] [Accepted: 08/12/2020] [Indexed: 11/19/2022]

Abstract

BACKGROUND

Individuals residing in areas with high prevalence of foodborne infection could have a higher risk of gut microbial translocation which may affect monocyte activation, gut immune recovery and intestinal epithelial cell damage. We aimed to measure alterations in microbial translocation, monocyte activation, gut immune recovery, and intestinal epithelial cell damage in HAART treated individuals.

METHODS

A prospective, single-arm, longitudinal, cohort study was conducted among antiretroviral naïve HIV-1 infected Thai participants. All participants were in chronic stage of HIV-1 infection before starting HAART. Data and samples were collected prior to initiation of HAART and then after 24 and 48 weeks of HAART. Plasma biomarkers for microbial translocation (16S rDNA and LBP), monocyte activation (sCD14) and intestinal epithelial cell damage (I-FABP) were evaluated. We measured circulating gut-homing CD4⁺ T cells and circulating gut-homing Th17 cells to assess recoveries of gut immunity and gut immunity to microbial pathogens.

RESULTS

The kinetic studies showed no reduction in the levels of plasma 16S rDNA, sCD14 or I-FABP, significant decrease of plasma LBP level, and slow but significant increases in the frequencies of circulating gut-homing CD4⁺ T cells and circulating gut-homing Th17 cells during 48 weeks of HAART. Dividing participants into low and high microbial translocation (low and high MT) groups at baseline, both groups showed persistent plasma levels of 16S rDNA, sCD14 and I-FABP, and significantly decreased plasma level of LBP. The low MT group had significantly increased frequencies of circulating gut-homing CD4⁺ T cells and circulating gut-homing Th17 cells during 48 weeks of HAART but this was not observed in the high MT group.

CONCLUSIONS

We demonstrated persistent high microbial translocation, monocyte activation and intestinal epithelial cell damage with slow gut immune recovery during successful short-term HAART. Additionally, gut immune recovery was apparently limited by high microbial translocation. Our findings emphasize the adverse impact of high microbial translocation on gut immune recovery and the necessity of establishing a novel therapeutic intervention to inhibit microbial translocation.

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Kroeze S, Wit FW, Rossouw TM, Steel HC, Kityo CM, Siwale M, Akanmu S, Mandaliya K, de Jager M, Ondoa P, Reiss P, Rinke de Wit TF, Kootstra N, Hamers RL. Plasma Biomarkers of Human Immunodeficiency Virus-Related Systemic Inflammation and Immune Activation in Sub-Saharan Africa Before and During Suppressive Antiretroviral Therapy. J Infect Dis 2020;220:1029-1033. [PMID: 31086991 PMCID: PMC6688057 DOI: 10.1093/infdis/jiz252] [Citation(s) in RCA: 30] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/15/2018] [Accepted: 05/13/2019] [Indexed: 02/03/2023] Open

Affiliation(s)

Stefanie Kroeze Amsterdam Institute for Global Health and Development and Department of Global Health, Amsterdam, the Netherlands
Ferdinand W Wit Amsterdam Institute for Global Health and Development and Department of Global Health, Amsterdam, the Netherlands.,Department of Internal Medicine, Division of Infectious Diseases, and Amsterdam Infection and Immunity Institute, Amsterdam, the Netherlands.,Stichting HIV Monitoring, Amsterdam, the Netherlands
Theresa M Rossouw Department of Immunology, Institute for Cellular and Molecular Medicine, University of Pretoria, Pretoria, South Africa
Helen C Steel Department of Immunology, Institute for Cellular and Molecular Medicine, University of Pretoria, Pretoria, South Africa
Cissy M Kityo Joint Clinical Research Centre, Kampala, Uganda
Margaret Siwale Lusaka Trust Hospital, Zambia
Sulaimon Akanmu Department of Haematology and Blood Transfusion, College of Medicine of the University of Lagos and the Lagos University Teaching Hospital, Nigeria
Kishor Mandaliya Coast Province General Hospital, Mombasa, Kenya
Marleen de Jager Muelmed Hospital, Pretoria, South Africa
Pascale Ondoa Amsterdam Institute for Global Health and Development and Department of Global Health, Amsterdam, the Netherlands.,African Society of Laboratory Medicine, Addis Ababa, Ethiopia
Peter Reiss Amsterdam Institute for Global Health and Development and Department of Global Health, Amsterdam, the Netherlands.,Department of Internal Medicine, Division of Infectious Diseases, and Amsterdam Infection and Immunity Institute, Amsterdam, the Netherlands.,Stichting HIV Monitoring, Amsterdam, the Netherlands
Tobias F Rinke de Wit Amsterdam Institute for Global Health and Development and Department of Global Health, Amsterdam, the Netherlands
Neeltje Kootstra Department of Experimental Immunology, Amsterdam UMC, University of Amsterdam, Amsterdam, the Netherlands
Raph L Hamers Amsterdam Institute for Global Health and Development and Department of Global Health, Amsterdam, the Netherlands.,Department of Internal Medicine, Division of Infectious Diseases, and Amsterdam Infection and Immunity Institute, Amsterdam, the Netherlands.,Eijkman-Oxford Clinical Research Unit, Jakarta, Indonesia.,Nuffield Department of Medicine, University of Oxford, United Kingdom

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Nabatanzi R, Bayigga L, Cose S, Rowland Jones S, Joloba M, Canderan G, Nakanjako D. Monocyte Dysfunction, Activation, and Inflammation After Long-Term Antiretroviral Therapy in an African Cohort. J Infect Dis 2020;220:1414-1419. [PMID: 31323092 PMCID: PMC6761975 DOI: 10.1093/infdis/jiz320] [Citation(s) in RCA: 21] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/20/2019] [Accepted: 07/03/2019] [Indexed: 11/12/2022] Open

Lawal IO, Stoltz AC, Sathekge MM. Molecular imaging of cardiovascular inflammation and infection in people living with HIV infection. Clin Transl Imaging 2020. [DOI: 10.1007/s40336-020-00370-4] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/20/2022]

Ryder MI, Shiboski C, Yao TJ, Moscicki AB. Current trends and new developments in HIV research and periodontal diseases. Periodontol 2000 2020;82:65-77. [PMID: 31850628 DOI: 10.1111/prd.12321] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]

Raehtz KD, Barrenäs F, Xu C, Busman-Sahay K, Valentine A, Law L, Ma D, Policicchio BB, Wijewardana V, Brocca-Cofano E, Trichel A, Gale M, Keele BF, Estes JD, Apetrei C, Pandrea I. African green monkeys avoid SIV disease progression by preventing intestinal dysfunction and maintaining mucosal barrier integrity. PLoS Pathog 2020;16:e1008333. [PMID: 32119719 PMCID: PMC7077871 DOI: 10.1371/journal.ppat.1008333] [Citation(s) in RCA: 30] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/30/2019] [Revised: 03/17/2020] [Accepted: 01/18/2020] [Indexed: 12/12/2022] Open

Abstract

Unlike HIV infection, SIV infection is generally nonpathogenic in natural hosts, such as African green monkeys (AGMs), despite life-long high viral replication. Lack of disease progression was reportedly based on the ability of SIV-infected AGMs to prevent gut dysfunction, avoiding microbial translocation and the associated systemic immune activation and chronic inflammation. Yet, the maintenance of gut integrity has never been documented, and the mechanism(s) by which gut integrity is preserved are unknown. We sought to investigate the early events of SIV infection in AGMs, specifically examining the impact of SIVsab infection on the gut mucosa. Twenty-nine adult male AGMs were intrarectally infected with SIVsab92018 and serially sacrificed at well-defined stages of SIV infection, preramp-up (1-3 days post-infection (dpi)), ramp-up (4-6 dpi), peak viremia (9-12 dpi), and early chronic SIV infection (46-55 dpi), to assess the levels of immune activation, apoptosis, epithelial damage and microbial translocation in the GI tract and peripheral lymph nodes. Tissue viral loads, plasma cytokines and plasma markers of gut dysfunction were also measured throughout the course of early infection. While a strong, but transient, interferon-based inflammatory response was observed, the levels of plasma markers linked to enteropathy did not increase. Accordingly, no significant increases in apoptosis of either mucosal enterocytes or lymphocytes, and no damage to the mucosal epithelium were documented during early SIVsab infection of AGMs. These findings were supported by RNAseq of the gut tissue, which found no significant alterations in gene expression that would indicate microbial translocation. Thus, for the first time, we confirmed that gut epithelial integrity is preserved, with no evidence of microbial translocation, in AGMs throughout early SIVsab infection. This might protect AGMs from developing intestinal dysfunction and the subsequent chronic inflammation that drives both HIV disease progression and HIV-associated comorbidities.

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Affiliation(s)

Kevin D. Raehtz Division of Infectious Diseases, Department of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, United States of America
Fredrik Barrenäs Department of Microbiology, University of Washington, Seattle, Washington, United States of America Department of Cell and Molecular Biology, Uppsala University, Uppsala, Sweden
Cuiling Xu Division of Infectious Diseases, Department of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, United States of America Department of Pathology, University of Pittsburgh, Pittsburgh, Pennsylvania, United States of America
Kathleen Busman-Sahay Vaccine and Gene Therapy Institute, Oregon Health and Science University, Portland, Oregon, United States of America Oregon National Primate Research Center, Oregon Health and Science University, Portland, Oregon, United States of America
Audrey Valentine Division of Infectious Diseases, Department of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, United States of America
Lynn Law Department of Immunology, University of Washington, Seattle, Washington, United States of America Center for Innate Immunity and Immune Diseases, University of Washington, Washington, United States of America
Dongzhu Ma Department of Orthopedic Surgery, University of Pittsburgh, Pittsburgh, Pennsylvania, United States of America
Benjamin B. Policicchio Department of Infectious Diseases and Microbiology, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, Pennsylvania, United States of America
Viskam Wijewardana Department of Pathology, University of Pittsburgh, Pittsburgh, Pennsylvania, United States of America
Egidio Brocca-Cofano Department of Pathology, University of Pittsburgh, Pittsburgh, Pennsylvania, United States of America
Anita Trichel Division of Laboratory Animal Resources, School of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, United States of America
Michael Gale Department of Immunology, University of Washington, Seattle, Washington, United States of America Center for Innate Immunity and Immune Diseases, University of Washington, Washington, United States of America Washington National Primate Research Center, University of Washington, Seattle, Washington, United States of America
Brandon F. Keele AIDS and Cancer Virus Program, Frederick National Laboratory of Cancer Research, Frederick, Maryland, United States of America
Jacob D. Estes Vaccine and Gene Therapy Institute, Oregon Health and Science University, Portland, Oregon, United States of America Oregon National Primate Research Center, Oregon Health and Science University, Portland, Oregon, United States of America
Cristian Apetrei Division of Infectious Diseases, Department of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, United States of America Department of Infectious Diseases and Microbiology, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, Pennsylvania, United States of America
Ivona Pandrea Department of Pathology, University of Pittsburgh, Pittsburgh, Pennsylvania, United States of America Department of Infectious Diseases and Microbiology, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, Pennsylvania, United States of America

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Oral and Gut Microbial Diversity and Immune Regulation in Patients with HIV on Antiretroviral Therapy. mSphere 2020;5:5/1/e00798-19. [PMID: 32024712 PMCID: PMC7002309 DOI: 10.1128/msphere.00798-19] [Citation(s) in RCA: 41] [Impact Index Per Article: 8.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/18/2022] Open

Abstract

A feedback loop between dysbiotic gut microbiota, increased translocation of microbial products such as lipopolysaccharide, and inflammation has been hypothesized to cause immune system dysfunction in early HIV infection. However, despite evidence of a chronic inflammatory phenotype in patients on antiretroviral therapy (ART), the role of oral microbiota in systemic immune activation and the relationship between oral and gut bacterial and fungal diversity have not been explored. Our study suggests a crucial role for oral bacterial and fungal communities in long-term systemic immune activation in patients on ART, expanding the current paradigm focused on gut bacteria. Our results indicate that interventions targeting both inflammation and microbial diversity are needed to mitigate oral inflammation-related comorbidities, particularly in HIV-positive patients. More broadly, these findings can bolster general models of microbiome-mediated chronic systemic immune activation and aid the development of precise microbiota-targeted interventions to reverse chronic inflammation.

Despite evidence of a chronic inflammatory phenotype in people living with HIV (PLWH) on antiretroviral therapy (ART), the role of oral microbiota in chronic immune activation has not been fully explored. We aimed to determine the relationship between oral and gut microbiome diversity and chronic systemic inflammation in ART-treated PLWH with prevalent severe periodontitis, an inflammatory condition commonly associated with HIV infection. We assessed bacterial and fungal communities at oral and gastrointestinal sites in a cohort (n = 52) of primarily postmenopausal women on ART using 16S rRNA and internal transcribed spacer (ITS) sequencing and measured cellular and soluble markers of inflammation and immune dysfunction. Linear mixed-effect regression and differential abundance analyses were used to associate clinical characteristics and immunological markers with bacterial and fungal diversity and community composition. Bacterial α-diversity in plaque, saliva, and gut was associated with different immunological markers, while mycobial diversity was not associated with soluble or cellular biomarkers of immune stimulation or T cell dysfunction. Furthermore, lipopolysaccharide-positive (LPS⁺) bacteria previously linked to inflammatory outcomes were enriched at oral sites in patients with severe periodontitis. Fungal α-diversity was reduced in plaque from teeth with higher clinical attachment loss, a marker of periodontitis, and in saliva and plaque from patients with a history of AIDS. Our results show that both bacterial and fungal oral microbiome communities likely play a role in chronic systemic immune activation in PLWH. Thus, interventions targeting both inflammation and the microbiome, particularly in the oral cavity, may be necessary to reduce chronic immune dysregulation in patients with HIV.

IMPORTANCE A feedback loop between dysbiotic gut microbiota, increased translocation of microbial products such as lipopolysaccharide, and inflammation has been hypothesized to cause immune system dysfunction in early HIV infection. However, despite evidence of a chronic inflammatory phenotype in patients on antiretroviral therapy (ART), the role of oral microbiota in systemic immune activation and the relationship between oral and gut bacterial and fungal diversity have not been explored. Our study suggests a crucial role for oral bacterial and fungal communities in long-term systemic immune activation in patients on ART, expanding the current paradigm focused on gut bacteria. Our results indicate that interventions targeting both inflammation and microbial diversity are needed to mitigate oral inflammation-related comorbidities, particularly in HIV-positive patients. More broadly, these findings can bolster general models of microbiome-mediated chronic systemic immune activation and aid the development of precise microbiota-targeted interventions to reverse chronic inflammation.

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Titanji B, Gavegnano C, Hsue P, Schinazi R, Marconi VC. Targeting Inflammation to Reduce Atherosclerotic Cardiovascular Risk in People With HIV Infection. J Am Heart Assoc 2020;9:e014873. [PMID: 31973607 PMCID: PMC7033865 DOI: 10.1161/jaha.119.014873] [Citation(s) in RCA: 24] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]

Letizia A, Eller MA, Polyak C, Eller LA, Creegan M, Dawson P, Bryant C, D K, Crowell TA, Lombardi K, Rono E, Robb ML, Michael NL, Maswai J, Ake JA. Biomarkers of Inflammation Correlate With Clinical Scoring Indices in Human Immunodeficiency Virus-Infected Kenyans. J Infect Dis 2019;219:284-294. [PMID: 30165548 DOI: 10.1093/infdis/jiy509] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/07/2018] [Accepted: 08/25/2018] [Indexed: 12/16/2022] Open

Affiliation(s)

Andrew Letizia Uniformed Services University of the Health Sciences, Bethesda
Michael A Eller US Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring.,Henry M. Jackson Foundation for the Advancement of Military Medicine, Bethesda
Christina Polyak Uniformed Services University of the Health Sciences, Bethesda.,US Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring.,Henry M. Jackson Foundation for the Advancement of Military Medicine, Bethesda
Leigh Anne Eller US Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring.,Henry M. Jackson Foundation for the Advancement of Military Medicine, Bethesda
Matthew Creegan US Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring.,Henry M. Jackson Foundation for the Advancement of Military Medicine, Bethesda
Peter Dawson Emmes Corporation, Rockville, Maryland
Christopher Bryant Emmes Corporation, Rockville, Maryland
Kim D US Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring.,Henry M. Jackson Foundation for the Advancement of Military Medicine, Bethesda
Trevor A Crowell Uniformed Services University of the Health Sciences, Bethesda.,US Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring.,Henry M. Jackson Foundation for the Advancement of Military Medicine, Bethesda
Kara Lombardi US Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring.,Henry M. Jackson Foundation for the Advancement of Military Medicine, Bethesda
Eric Rono Kenya Medical Research Institute/Walter Reed Project.,HJF Medical Research International, Inc, Kericho, Kenya
Merlin L Robb US Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring.,Henry M. Jackson Foundation for the Advancement of Military Medicine, Bethesda
Nelson L Michael US Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring
Jonah Maswai Kenya Medical Research Institute/Walter Reed Project.,HJF Medical Research International, Inc, Kericho, Kenya
Julie A Ake US Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring

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Weinberg A, Huo Y, Kacanek D, Patel K, Watts DH, Wara D, Hoffman RM, Klawitter J, Christians U, IMPAACT P1025 Team. Brief Report: Markers of Spontaneous Preterm Delivery in Women Living With HIV: Relationship With Protease Inhibitors and Vitamin D. J Acquir Immune Defic Syndr 2019;82:181-187. [PMID: 31513074 PMCID: PMC6760328 DOI: 10.1097/qai.0000000000002111] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]

Siedner MJ, Zanni M, Tracy RP, Kwon DS, Tsai AC, Kakuhire B, Hunt PW, Okello S. Increased Systemic Inflammation and Gut Permeability Among Women With Treated HIV Infection in Rural Uganda. J Infect Dis 2019;218:922-926. [PMID: 29718342 DOI: 10.1093/infdis/jiy244] [Citation(s) in RCA: 41] [Impact Index Per Article: 6.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/28/2018] [Accepted: 04/25/2018] [Indexed: 11/13/2022] Open

Iacob S, Iacob DG. Infectious Threats, the Intestinal Barrier, and Its Trojan Horse: Dysbiosis. Front Microbiol 2019;10:1676. [PMID: 31447793 PMCID: PMC6692454 DOI: 10.3389/fmicb.2019.01676] [Citation(s) in RCA: 93] [Impact Index Per Article: 15.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/14/2019] [Accepted: 07/08/2019] [Indexed: 02/06/2023] Open

Abstract

The ecosystem of the gut microbiota consists of diverse intestinal species with multiple metabolic and immunologic activities and it is closely connected with the intestinal epithelia and mucosal immune response, with which it builds a complex barrier against intestinal pathogenic bacteria. The microbiota ensures the integrity of the gut barrier through multiple mechanisms, either by releasing antibacterial molecules (bacteriocins) and anti-inflammatory short-chain fatty acids or by activating essential cell receptors for the immune response. Experimental studies have confirmed the role of the intestinal microbiota in the epigenetic modulation of the gut barrier through posttranslational histone modifications and regulatory mechanisms induced by epithelial miRNA in the epithelial lumen. Any quantitative or functional changes of the intestinal microbiota, referred to as dysbiosis, alter the immune response, decrease epithelial permeability and destabilize intestinal homeostasis. Consequently, the overgrowth of pathobionts (Staphylococcus, Pseudomonas, and Escherichia coli) favors intestinal translocations with Gram negative bacteria or their endotoxins and could trigger sepsis, septic shock, secondary peritonitis, or various intestinal infections. Intestinal infections also induce epithelial lesions and perpetuate the risk of bacterial translocation and dysbiosis through epithelial ischemia and pro-inflammatory cytokines. Furthermore, the decline of protective anaerobic bacteria (Bifidobacterium and Lactobacillus) and inadequate release of immune modulators (such as butyrate) affects the release of antimicrobial peptides, de-represses microbial virulence factors and alters the innate immune response. As a result, intestinal germs modulate liver pathology and represent a common etiology of infections in HIV immunosuppressed patients. Antibiotic and antiretroviral treatments also promote intestinal dysbiosis, followed by the selection of resistant germs which could later become a source of infections. The current article addresses the strong correlations between the intestinal barrier and the microbiota and discusses the role of dysbiosis in destabilizing the intestinal barrier and promoting infectious diseases.

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Masenga SK, Hamooya BM, Nzala S, Kwenda G, Heimburger DC, Mutale W, Munsaka SM, Koethe JR, Kirabo A. Patho-immune Mechanisms of Hypertension in HIV: a Systematic and Thematic Review. Curr Hypertens Rep 2019;21:56. [PMID: 31165257 PMCID: PMC6548744 DOI: 10.1007/s11906-019-0956-5] [Citation(s) in RCA: 45] [Impact Index Per Article: 7.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/17/2022]

Distinct gut microbiota profile in antiretroviral therapy-treated perinatally HIV-infected patients associated with cardiac and inflammatory biomarkers. AIDS 2019;33:1001-1011. [PMID: 30946154 DOI: 10.1097/qad.0000000000002131] [Citation(s) in RCA: 24] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]

Weiner LD, Retuerto M, Hager CL, El Kamari V, Shan L, Sattar A, Kulkarni M, Funderburg N, Ghannoum MA, Dirajlal-Fargo S, McComsey GA. Fungal Translocation Is Associated with Immune Activation and Systemic Inflammation in Treated HIV. AIDS Res Hum Retroviruses 2019;35:461-472. [PMID: 30784316 DOI: 10.1089/aid.2018.0252] [Citation(s) in RCA: 29] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022] Open