Analytical treatment interruption (ATI) among African women with early ART initiation with or without VRC01 circulating at HIV acquisition: study design and early observations of viral rebound and control


BACKGROUND: Viremia rebounds rapidly in most people living with HIV upon ART cessation. Early ART initiation is associated with ART-free virologic control, and broadly neutralizing anti-HIV-1 antibodies (bnAbs) may modulate immune responses to HIV. Durable ART-free virologic control has been observed in 20-25% of African women in some cohorts, significantly higher than in other populations. The HVTN 703/HPTN 081 AMP trial evaluated VRC01 bnAb-mediated HIV-1 prevention among African women; those who acquired HIV were linked to early ART. With African community, investigator, ethics and regulatory collaborators, an AMP ATI (HVTN 805/HPTN 093/A5390) was designed to evaluate whether early ART +/- VRC01 circulating at HIV acquisition is associated with virologic control post-ATI and to assess underlying immunologic and virologic dynamics.
METHODS: AMP ATI eligibility includes African women with an estimated HIV acquisition date within 8 weeks of receiving VRC01 or placebo in AMP, early ART initiation and '¥1 year of viral suppression. Participants complete an NNRTI switch, as needed, then stop ART and receive frequent viral load (VL) and CD4+ T-cell count monitoring. ART re-initiation criteria include CD4<250, VL>1,000 for 4 weeks without 0.5log decline, or participant/clinician request to restart ART.
RESULTS: Nine participants from South Africa, Malawi, Botswana and Zimbabwe have enrolled, thus far; 7/9 met ART re-initiation criteria (n=5 for VL; n=2 for participant/clinician request). One participant requesting ART re-initiation had tenofovir levels consistent with ART use during ATI. Median time to confirmed VL>200 was 7.3 weeks (range 2.7-20.9+). Median time to meet virologic ART re-initiation criteria was 17.1 weeks (11-21.3). ART was reinitiated a median of 7 days later; all re-suppressed. No SAEs or Grade '¥2 related AEs were reported. See Figure 1.

CONCLUSIONS: In a safe and well-tolerated ongoing ATI developed with local stakeholder engagement, African women with early ART initiation +/- prior VRC01 exhibit evidence of viral rebound and control.

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