Impact of antiretroviral therapy during acute or early HIV infection on virologic and immunologic outcomes: Results from a multinational clinical trial

Crowell T.A.; Ritz J.; Zheng L.; Naqvi A.; Cyktor J.C.; Puleo J.; Clagett B.; Lama J.R.; Kanyama C.; Little S.J.; Cohn S.E.; Riddler S.A.; Collier A.C.; Heath S.L.; Tantivitayakul P.; Grinsztejn B.; Arduino R.C.; Rooney J.F.; Van Zyl G.U.; Coombs R.W.; Fox L.; Ananworanich J.; Eron J.J.; Sieg S.F.; Mellors J.W.; Daar E.S. · AIDS (2024) · DOI: 10.1097/qad.0000000000003881

Resumen

Objective:To assess how antiretroviral therapy (ART) initiation during acute or early HIV infection (AEHI) affects the viral reservoir and host immune responses.Design:Single-arm trial of ART initiation during AEHI at 30 sites in the Americas, Africa, and Asia.Methods:HIV DNA was measured at week 48 of ART in 5 million CD4+T cells by sensitive qPCR assays targeting HIV gag and pol. Peripheral blood mononuclear cells were stimulated with potential HIV T cell epitope peptide pools consisting of env, gag, nef, and pol peptides and stained for expression of CD3, CD4, CD8, and intracellular cytokines/chemokines.Results:From 2017 to 2019, 188 participants initiated ART during Fiebig stages I (n = 6), II (n = 43), III (n = 56), IV (n = 23), and V (n = 60). Median age was 27 years (interquartile range 23-38), 27 (14%) participants were female, and 180 (97%) cisgender. Among 154 virally suppressed participants at week 48, 100% had detectable HIV gag or pol DNA. Participants treated during Fiebig I had the lowest HIV DNA levels (P < 0.001). Week 48 HIV DNA mostly did not correlate with concurrent CD4+or CD8+T cell HIV-specific immune responses (rho range -0.11 to +0.19, all P > 0.025). At week 48, the magnitude, but not polyfunctionality, of HIV-specific T cell responses was moderately reduced among participants who initiated ART earliest.Conclusion:Earlier ART initiation during AEHI reduced but did not eliminate the persistence of HIV-infected cells in blood. These findings explain the rapid viral rebound observed after ART cessation in early-treated individuals with undetectable HIV DNA by less sensitive methods.