Antiretroviral therapy (ART) initiated during acute or early HIV infection (AEHI) may limit HIV reservoir formation and facilitate HIV remission. We evaluated HIV DNA levels in blood at and after suppressive ART initiation across AEHI stages in a multinational study.
ACTG 5354 enrolled adults with AEHI at 30 sites in the Americas, Africa, and Southeast Asia. Participants initiated ART during AEHI, either with a study-provided integrase inhibitor-based regimen or another prescribed regimen. Fiebig stage at ART initiation was retroactively assigned by centralized testing and categorized per protocol as Group 1 (Fiebig I/II), Group 2 (Fiebig III/IV) or Group 3 (Fiebig V). The primary study endpoint was undetectable HIV DNA at week 48 of ART in 5 million purified CD4+ T cells by sensitive qPCR assays targeting HIV gag and pol. To assess HIV-specific immune responses, peripheral blood mononuclear cells were stimulated with potential T cell epitope peptide pools and stained for expression of CD3, CD4 and CD8 and intracellular interferon-gamma.
From January 2017 to December 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%) were female, and 96% cisgender. Fiebig I participants had lower pre-ART HIV gag DNA than participants in all other Fiebig stages (all p<0.05) and trended toward lower pre-ART HIV pol DNA as well (all p<0.10). Among 153 participants with HIV RNA <50 copies/mL without protocol-defined ART interruption, 100% had detectable HIV gag or pol DNA at 48 weeks of ART with negative intra-assay controls. Participants who started ART during the earliest Groups and Fiebig stages had significantly lower HIV gag and pol DNA levels at 48 weeks (all trend tests p<0.001, Figure). Week 48 HIV DNA did not correlate with CD4+ or CD8+ T cell interferon-gamma responses to env, gag, nef, or pol peptide stimulation (rho range -0.10 to +0.14, all p>0.05).
ART initiation in earlier stages of AEHI reduced but did not eliminate the persistence of HIV-infected cells in blood. In contrast to prior studies, sensitive and specific qPCR assays performed on a large number of CD4+ T cells detected HIV DNA in all participants after 48 weeks of ART regardless of Fiebig stage at ART initiation. These findings may explain why rapid viral rebound has been observed after ART cessation in early-treated individuals with undetectable HIV DNA by less sensitive methods.