Temporary increase in circulating replication-competent latent HIV-infected resting CD4+ T cells after switch to an integrase inhibitor based antiretroviral regimen

The principal barrier to an HIV cure is the presence of a latent viral reservoir (LVR) made up primarily of latently infected resting CD4+ (rCD4) T-cells. Studies in the United States have shown that the LVR decays slowly (half-life=3.8 years), but this rate in African populations has been understudied. This study examined longitudinal changes in the inducible replication competent LVR (RC-LVR) of ART-suppressed Ugandans living with HIV (n=88) from 2015-2020 using the quantitative viral outgrowth assay, which measures infectious units per million (IUPM) rCD4 T-cells. In addition, outgrowth viruses were examined with site-directed next-generation sequencing to assess for possible ongoing viral evolution. During the study period (2018-19), Uganda instituted a nationwide rollout of first-line ART consisting of Dolutegravir (DTG) with two NRTI, which replaced the previous regimen that consisted of one NNRTI and the same two NRTI. Changes in the RC-LVR were analyzed using two versions of a novel Bayesian model that estimated the decay rate over time on ART as a single, linear rate (model A) or allowing for an inflection at time of DTG initiation (model B). Model A estimated the population-level slope of RC-LVR change as a non-significant positive increase. This positive slope was due to a temporary increase in the RC-LVR that occurred 0-12 months post-DTG initiation (pAuthor SummaryHIV is a largely incurable infection despite the use of highly successful antiretroviral drugs (ARV) due to the presence of a population of long-living resting CD4+ T cells, which can harbor a complete copy of the virus integrated into the host cell’s DNA. We examined changes in the levels of these cells, referred to as the latent viral reservoir, in a group of ARV-treated Ugandans living with HIV. During this examination, Uganda authorities switched the backbone drug used in ARV regimens to a different class of drug that blocks the ability of the virus to integrate into the cell’s DNA. We found that for approximately a year after this switch to the new drug, there was a temporary spike in the size of the latent viral reservoir despite the new drug continuing to completely suppress viral replication with no apparent adverse clinical effects.