Factors influencing virologic control during analytical treatment interruptions in HIV cure trials - a pooled analysis of individual level data.

Abstract

Background: Achieving antiretroviral therapy (ART)-free virologic control remains a central goal in human immunodeficiency virus (HIV) cure research. To identify factors associated with time to detectable viremia and time to loss of virologic control, we conducted a pooled analysis of six interventional trials that included analytical ART interruption.

Methods: We determined factors influencing time to detectable viremia (plasma HIV-RNA ≥50 copies/mL) and loss of virologic control (two consecutive measurements of plasma HIV-RNA ≥5,000 copies/mL or restart of ART) using cox proportional hazard regression.

Results: Among the 91 included participants we found that high levels of total HIV-DNA (≥750 copies) and intact proviral DNA (≥80 copies/106 CD4+ T cells) were both associated with shorter time to detectable viremia (HR=1.98, 95% confidence interval [CI]: 1.22, 3.22; HR=1.67, 95% CI: 1.08, 2.58, respectively). Total HIV-DNA ≥750 copies/106 CD4+ T cells also predicted shorter time to loss of virologic control (HR=1.64, 95% CI: 1.01, 2.67); as did longer time ≥1 year from HIV diagnosis to ART start (HR=1.56, 95% CI: 1.02, 2.39). Having received histone deacetylase inhibitors predicted shorter time to loss of virologic control (HR=2.22, 95% CI: 1.12, 4.41), while broadly neutralizing anti-HIV-1 antibody (bNAb) treatment at ART initiation of individuals harboring 3BNC117-sensitive viruses trended towards delayed time to loss of virologic control (HR=0.32, 95% CI: 0.10, 1.01).

Conclusions: Our findings highlight the positive impact of early ART and low HIV reservoirs on time to rebound among people undergoing ATI and provides new insight into therapeutic interventions aimed at achieving virologic control.