Background
Early ART initiation and broadly neutralizing anti-HIV antibodies (bnAbs) are associated with later ART-free HIV control more frequently in African women with clade C HIV compared to men with clade B HIV. T cells may mediate HIV control, but data among women are limited. We thus measured T cell responses in women and MSM+TG during analytical treatment interruption (ATI).
Methods
Eligible participants had acquired HIV within ~8wks of receiving VRC01 bnAb or placebo in the AMP HIV prevention efficacy trials, initiated ART early, and were virally suppressed ≥1 year. ART was paused under intensive monitoring (ATI), then reinitiated for CD4<250, VL>1000 for 4wks without 0.5log decline, or participant/clinician request. We assessed HIV-specific T cell responses (IFN-γ and/or IL-2 expression) by intracellular cytokine staining after stimulation with peptide pools to all HIV proteins. We calculated total response as the sum across responses to each protein.
Results
Eleven women in southern Africa and 17 MSM+TG in Peru stopped ART. Median time to confirmed VL>200 was 5.4 weeks (range 2.3-112) in women and 4.3 weeks (0.1-18) in MSM+TG. Maximum HIV-specific CD8+ & CD4+ T cell responses during ATI did not differ by VRC01 vs. placebo in either cohort, but in women, the increase in CD8+ from baseline was greater for Gag (10-fold; p=0.024) and Vif (4.6-fold; p=0.024) in those who received VRC01 in AMP. HIV-specific CD4+ responses were low (max <0.5%) compared to CD8+ responses (mainly 1-5%, max 15%) during ATI. Time to ART re-initiation did not correlate with CD8+ (Spearman r=0.5; p=0.18) or CD4+ (r=0.45; p=0.23) responses. Two of 11 women (18%; 95% CI 5.1-47.7%) maintained VL<200 off ART for ≥32 weeks (“controllers”); no MSM+TG (0/17; 95% CI 0.0-18.4%) exhibited control on ATI. Compared to non-controllers, both controllers had higher frequency CD8+ responses to Env (≥0.8% of CD8+ cells) & Pol (≥10%) and, for the VRC01-recipient controller, also to Gag (4%). Both controllers’ HIV-specific CD8+ responses preceded viral rebound; non-controllers’ CD8+ responses followed rebound. Both controllers & non-controllers had HLA alleles associated with protection (eg, B*14:02, B*44:03, B*58:01, DRB1*13-DQB1*06) &/or susceptibility (eg, B*58:02).
Conclusions
Differences in CD8+ (but not CD4+) responses may partly explain why the proportion of controllers differs between Peruvian MSM+TG (0%) and African women (18%) in this post-AMP ATI. Study of T cell responses may identify biomarkers that predict control on ATI.
Table or Figure
