Background
Post-treatment ART-free HIV control (PTC) is uncommon. Viral and immune dynamics in analytical treatment interruption (ATI) inform HIV cure strategies and may vary across populations, yet women and MSM in the global South are underrepresented in ATIs. The AMP ATIs help address these gaps.
Methods
The Antibody Mediated Prevention (AMP) ATIs enrolled women in Southern Africa (HVTN 805/HPTN 093/A5393) and MSM in Peru (HVTN 804/HPTN 095/A5390). Participants (ppts) received VRC01 or placebo within 8 weeks of estimated HIV acquisition, initiated ART early and were virally suppressed on ART for ≥1 year before ATI. ART was restarted for VL>1000 for 4 weeks without 0.5 log10 decline or for ppt/clinician choice. Rebound dynamics were assessed with a nonlinear mixed-effects model including fixed effects for HIV control status, VRC01 vs. placebo and global region, and a ppt-level random effect. Longitudinal HIV-specific CD8+ T cell responses were assessed by ICS; autologous neutralizing antibody (anAb) responses against transmitted/founder (TF) and rebound viruses were assessed by TZM-bl after ART-DEX to clear residual ART.
Results
Eleven women and 16 MSM initiated ATI; at day 14 (day 84) of ATI, 91% (28%) of women and 80% (0%) of MSM had VL<40 copies/mL. One woman restarted ART while VL<40. Of 10 women in Africa and 16 MSM in Peru who rebounded on ATI, two women and no MSM controlled HIV (≥24 weeks of VL<200 off ART). Rebound slope was 35-fold lower for controllers vs. non-controllers (p<0.001) in Africa and 2-fold lower for African women vs. Peruvian MSM (p=0.025) and did not differ by VRC01 vs. placebo overall or within each region. In non-controllers, CD8+ T cell response magnitudes increased from baseline after viral rebound, whereas in controllers, they increased before rebound. AnAb responses were heterogeneous. In Africa, 7/10 ppts’ baseline anAb titers were higher against rebound viruses than TFs; anAb titers increased with rebound in 10/10; after ART restart, 8/10 ppts’ anAbs were higher against TFs than rebound viruses.
Conclusions
Rebound patterns vary across global populations. In the AMP ATIs, African women exhibited more frequent PTC and lower rebound slopes than Peruvian MSM. In African women, viral rebound boosted anAb responses against TFs, suggesting early antigenic imprinting. Controllers had markedly lower rebound slopes and CD8+ T cell responses that preceded rebound, suggesting a cellular contribution to control. Our data from the global South informs global cure strategies.
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