Effect of Delayed Antiretroviral Therapy Initiation on Anti-CD4 Autoantibodies in Antiretroviral Therapy-Naïve People With HIV.

Abstract

We previously identified anti-CD4 autoantibodies in antiretroviral therapy (ART)-naïve people with HIV (PWH) with CD4<100 cells/µL using luciferase immunoprecipitation systems (LIPS). The influence of ART initiation on anti-CD4 autoantibodies and their impact on CD4 recovery in PWH with higher CD4 counts is unclear. In the Strategic Timing of Antiretroviral Treatment (START) trial, ART-naïve PWH with CD4>500 cells/µL were randomized to start ART immediately (immediate) or delay until CD4<350 cells/µL or AIDS (deferred). In a subset of participants, we measured anti-CD4 autoantibodies using LIPS from plasma samples collected at baseline and month 24. We used logistic regression models to evaluate associations with the presence of anti-CD4 autoantibodies and to compare month 24 anti-CD4 autoantibodies between treatment groups. In the immediate group, the mean change in CD4 counts from baseline to month 24 was compared by baseline anti-CD4 autoantibody serostatus. Baseline anti-CD4 autoantibody prevalence in 1199 participants (600 immediate, 599 deferred) was 41%; anti-CD4 autoantibodies were higher with recent HIV infection and among participants in Africa. At month 24, anti-CD4 autoantibody prevalence had decreased to 26% in the immediate and 31% in the deferred group (OR=1.91, p<0.001). Participants with recent HIV infection had larger decreases in anti-CD4 autoantibodies (p<0.001). There was no difference in CD4 recovery from baseline to month 24 by baseline anti-CD4 autoantibodies within the immediate group. Anti-CD4 autoantibodies are common in untreated PWH with high CD4 counts; however, with ART use, their prevalence decreases. Anti-CD4 autoantibodies are not associated with CD4 recovery in PWH with CD4>500 cells/µL initiating ART.