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

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.