Assessing advances in three decades of clinical antiretroviral therapy on the HIV-1 reservoir

BACKGROUNDAntiretroviral therapy (ART) has improved the clinical management of HIV-1 infection. However, little is known about how the latest ART recommendations affect the heterogeneity of the HIV-1 reservoir size.METHODSWe used a complete statistical approach to outline parameters underlying the diversity in HIV-1 reservoir size in a cohort of 892 people with HIV-1 (PWH) on suppressive ART for more than 3 years. Total HIV-1-DNA levels were measured in PBMCs using digital droplet PCR (ddPCR).RESULTSWe classified 179 (20%) participants as being low viral reservoir treated (LoViReT) (<50 HIV-1-DNA copies/106 PBMCs). Twenty variables were collected to explore their association with the LoViReT phenotype using machine learning approaches. LoViReT status was closely associated with higher nadir CD4, lower zenith pre-ART viral load, lower CD4 recovery, shorter time from diagnosis to undetectable viral load, and initiation of treatment with an integrase inhibitor-containing (InSTI-containing) regimen. Initiation of ART with any InSTI was also linked with a shorter time to undetectable viremia. Locally estimated scatterplot smoothing (LOESS) regression revealed a progressive reduction in the size of the HIV-1 reservoir in individuals who started ART after 2007. Similarly, a higher nadir CD4 and a shorter time to undetectable viremia were observed when treatment was initiated after that year.CONCLUSIONOur findings demonstrate that the progressive implementation of earlier, universal treatment at diagnosis and the use of InSTIs affected the size of the HIV-1 reservoir. Our work shows that effective management of infection is the first step toward reducing the reservoir and brings us closer to achieving a cure.FUNDINGNIH; Division of AIDS at the National Institute of Allergy and Infectious Diseases (NIAID), NIH; Merck Sharp & Dohme.

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Publication Details

Journal
Journal of Clinical Investigation
Published
2024-11-29
DOI
https://doi.org/10.1172/jci183952
Citations
5
Primary Topic
HIV Research and Treatment
Type
article
Field-Weighted Citation Impact
1.47

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article

Assessing advances in three decades of clinical antiretroviral therapy on the HIV-1 reservoir

Maria Carmen Puertas, Lucía Bailón, Bonaventura Clotet, Sara Morón‐López et al.
5 citations
Journal of Clinical Investigation
HIV Research and Treatment
1.47
article

Assessing advances in three decades of clinical antiretroviral therapy on the HIV-1 reservoir

Maria Carmen Puertas, Lucía Bailón, Bonaventura Clotet, Sara Morón‐López, Maria C. García-Guerrero, Rafick‐Pierre Sékaly, Beatriz Mothe, Irene González-Navarro, María Salgado, Eulàlia Grau, Vincent C. Marconi, Linos Vandekerckhove, Lorna Leal, Víctor Urrea, Javier Martínez‐Picado, Cristina Gálvez, Díez García F, Cristina Miranda
article en
5 citations

Abstract

BACKGROUNDAntiretroviral therapy (ART) has improved the clinical management of HIV-1 infection. However, little is known about how the latest ART recommendations affect the heterogeneity of the HIV-1 reservoir size.METHODSWe used a complete statistical approach to outline parameters underlying the diversity in HIV-1 reservoir size in a cohort of 892 people with HIV-1 (PWH) on suppressive ART for more than 3 years. Total HIV-1-DNA levels were measured in PBMCs using digital droplet PCR (ddPCR).RESULTSWe classified 179 (20%) participants as being low viral reservoir treated (LoViReT) (<50 HIV-1-DNA copies/106 PBMCs). Twenty variables were collected to explore their association with the LoViReT phenotype using machine learning approaches. LoViReT status was closely associated with higher nadir CD4, lower zenith pre-ART viral load, lower CD4 recovery, shorter time from diagnosis to undetectable viral load, and initiation of treatment with an integrase inhibitor-containing (InSTI-containing) regimen. Initiation of ART with any InSTI was also linked with a shorter time to undetectable viremia. Locally estimated scatterplot smoothing (LOESS) regression revealed a progressive reduction in the size of the HIV-1 reservoir in individuals who started ART after 2007. Similarly, a higher nadir CD4 and a shorter time to undetectable viremia were observed when treatment was initiated after that year.CONCLUSIONOur findings demonstrate that the progressive implementation of earlier, universal treatment at diagnosis and the use of InSTIs affected the size of the HIV-1 reservoir. Our work shows that effective management of infection is the first step toward reducing the reservoir and brings us closer to achieving a cure.FUNDINGNIH; Division of AIDS at the National Institute of Allergy and Infectious Diseases (NIAID), NIH; Merck Sharp & Dohme.

Journal of Clinical InvestigationVol. 135(2)
Universitat de Vic - Universitat Central de Catalunya (ES), Institució Catalana de Recerca i Estudis Avançats (ES), Universitat Autònoma de Barcelona (ES), Emory University (US), Veterans Health Administration (US), Ghent University Hospital (BE), Instituto de Salud Carlos III (ES), IrsiCaixa (ES), Centre for Biomedical Network Research on Rare Diseases (ES), Hospital Clínic de Barcelona (ES), Institut d'Investigació en Ciències de la Salut Germans Trias i Pujol (ES), Atlanta VA Medical Center (US), Hospital Universitari Germans Trias i Pujol (ES), Fundació Lluita contra les Infeccions (ES), Advanced Dermatology (US), Universitat de Barcelona (ES)
Eli Lilly and Company, AstraZeneca, Gilead Sciences, ViiV Healthcare, Grifols, National Institutes of Health, Merck Sharp and Dohme
Good health and well-being
Openalex Percentile: Top 17%
HIV Research and Treatment
1.47
DOIOpen Access PDFOpenAlex
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