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

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Abstract

BACKGROUND. Antiretroviral 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 HIV-1 reservoir size. METHODS. We used a complete statistical approach to outline parameters underlying diversity in HIV-1 reservoir size in a cohort of 892 people with HIV-1 (PWH) on suppressive ART for >3 years. Total HIV-1-DNA levels were measured in PBMCs using digital droplet PCR (ddPCR). RESULTS. We classified 179 (20%) participants as 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. Nadir CD4 and zenith pre-ART viral load were closely associated with LoViReT status, with lower CD4 recovery, shorter time from diagnosis to undetectable viral load, and initiation of treatment with an integrase inhibitor (InSTI)–containing regimen. Initiating ART with any InSTI was also associated with 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, higher nadir CD4 and shorter time to undetectable viremia were observed when treatment was initiated after that year. CONCLUSION. Our findings demonstrate that the progressive implementation of earlier, universal treatment at diagnosis and the use of InSTIs affect 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. FUNDING. U.S. National Institutes of Health, Division of AIDS at the National Institute of Allergy and Infectious Diseases, Merck Sharp & Dohme.

Authors

Irene González-Navarro, Víctor Urrea, Cristina Gálvez, Maria del Carmen Garcia-Guerrero, Sara Morón-López, Maria C. Puertas, Eulàlia Grau, Beatriz Mothe, Lucía Bailón, Cristina Miranda, Felipe García, Lorna Leal, Linos Vandekerckhove, Vincent C. Marconi, Rafick P. Sekaly, Bonaventura Clotet, Javier Martinez-Picado, Maria Salgado