Effects of different treatment regimens on T cell function in acute HIV infection.

Abstract

In HIV-infected individuals, anti-retroviral therapy (ART) is effective in maintaining low viral loads, restoring CD4+ T cell counts, and prolonging life. However, chronic inflammation and immune dysfunction persist even after years of successful ART. Previous studies have suggested that early initiation of ART may result in improved immune reconstitution, but whether more rapid suppression of viral load during early treatment also improves immunological outcomes is unknown. In this study we compare the effects of two regimens initiated during acute infection on T cell phenotype and function. Regimen 1 (n=30) is a non-nucleoside reverse transcriptase inhibitor (NNRTI)-based regimen and Regimen 2 (n=30) combines an integrase strand transfer inhibitor (INSTI) with nucleoside reverse transcriptase inhibitors (NRTIs). NRTIs and NNRTIs inhibit reverse transcription of viral RNA to DNA in the infected cell, while INSTIs block integration of viral DNA into the host genome. Since Regimen 2 targets multiple stages of the viral life cycle, we hypothesize that more rapid viral suppression may be achieved with this treatment schedule. In a cross-sectional study performed 96 weeks after treatment initiation, we are comparing the effects of the two regimens on T cell activation (CD25, CD69, CD38, HLA-DR), exhaustion (PD-1, Tim-3, CD160, T-bet, Eomes), and proliferation using standardized flow cytometry panels. This study will provide valuable insights into the relationship between viral decay kinetics and immune preservation during acute infection, informing the design of future ART regimens.