Background
Viral suppression without continuous antiretroviral therapy (ART) is an unmet need among people with HIV (PWH), and analytical treatment interruption (ATI) is used for evaluating potential therapies for long-term virologic control without lifelong ART. This phase 2 trial evaluated the safety and efficacy of budigalimab ± trosunilimab to maintain suppression in PWH undergoing ATI. Here, we describe key virologic outcomes, including retroviral rebound syndrome (RRS).
Methods
In this double-blind, placebo-controlled trial, 142 PWH (14.1% female) who were virologically suppressed on stable ART were randomized to 4 treatment and 1 placebo arms. On Day 1, all PWH stopped ART and received budigalimab IV or placebo Q2Wx4 doses and trosunilimab IV or placebo Q4Wx3 doses over 8 weeks (wks). PWH continued ATI until ART restart criteria were met (or until study end, planned Wk 112). Plasma viral load, CD4+ T-cell count, and safety were monitored weekly in the first 12 weeks of ATI. Viral kinetics during ATI were trended per treatment arm. Safety endpoints included RRS during ATI and virologic failure after ART restart (confirmed pVL≥200 cp/mL after suppression or failure to re-suppress within 24 wks).
Results
Among 141 PWH who underwent ATI, 16 (11.3%) experienced RRS (Table). Events were observed across all arms and most were grade 1-2. Two RRS events were assessed as serious, but only 1 (grade 4) was considered related to study treatment by the investigator. All RRS events, regardless of grade, resolved (per investigator assessment) following ART restart. Median time to viral rebound (pVL ≥1000 cp/mL) and median peak pVL prior to ART restart were generally similar across arms, while the proportion of PWH with a very elevated pVL (≥100,000 cp/mL) as the primary reason for ART restart was 49/141 (34.8%). Eight (5.7%) PWH had a confirmed CD4+ T-cell count <350 cells/μL. Protocol-defined virologic failure post-ART restart occurred in 15/141 (10.6%) PWH across all arms. No PWH experienced rebound after re-suppression on ART, and all but 2 PWH attained re-suppression based on a single pVL measure.
Conclusions
In a large phase 2 global RCT of budigalimab ± trosunilimab with a carefully monitored ATI, RRS events were generally mild and all resolved following ART restart. These findings demonstrate that while RRS can occur when ART is stopped in the context of a clinical trial, ATI is safe with close monitoring.
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