Viral and immune predictors of HIV posttreatment control.

Abstract

Purpose of review: This review focuses on the viral and immune factors influencing HIV posttreatment control (PTC), a rare condition where individuals maintain viral suppression after discontinuing antiretroviral therapy (ART).

Recent findings: Studies demonstrate that early ART initiation leads to smaller HIV reservoirs and delayed viral rebound in PTCs. Virologically, PTCs harbor smaller HIV reservoirs and show lower levels of reservoir transcriptional activity compared with posttreatment noncontrollers. Immunologically, PTCs exhibit distinct T-cell dynamics, with reduced CD4+ and CD8+ T-cell activation and exhaustion, enhanced natural killer (NK) cell activity, and enhanced proliferative responses of HIV-specific CD8+ T cells post-ART interruption. Additionally, humoral immunity, particularly the development of autologous neutralizing antibodies (aNAbs), plays a role in viral control, though broadly neutralizing antibodies (bnAbs) are rare.

Summary: The mechanisms behind posttreatment control are multifactorial, involving virological and immunological factors. Early ART initiation, a smaller and less transcriptionally active HIV reservoir, and immune responses including proliferative T-cell activity and NK cell function are key contributors to achieving ART-free HIV remission.