(A-124) Evaluating effectiveness of ibalizumab among highly treatment experienced people with HIV: an externally controlled trial

Background: Ibalizumab (IBA) is a monoclonal antibody approved for heavily treatment experienced (HTE) people with ongoing HIV viremia and multidrug resistance. The benefit of IBA relative to other antiretrovirals (ARV) is unknown because ethical considerations prevented the inclusion of comparison arms without IBA use in clinical trials.

Objectives: To compare the effectiveness of IBA-containing regimens to non-IBA-containing regimens among HTE individuals using external comparators (EC) identified from routine clinical care.

Methods: This external comparison analysis included participants from two IBA clinical trials without non-IBA arms, as well as comparator individuals from the OPERA® cohort (real-world data from electronic health records). Individuals who received regimens containing 800 mg IBA every two weeks from the TMB-202 (24 weeks) and TMB-301/311 (24 weeks, optional extension >96 weeks) trials (treated) were compared to HTE individuals on non-IBA-containing regimens in routine care (EC). Virologic outcomes included the achievement of viral undetectability (viral load [VL] < 50 copies/mL) and suppression (VL < 200) within 24 weeks of follow-up, as well as loss of undetectability (VL ≥50) or suppression (VL ≥200) at any point after their respective achievement. Cox proportional hazard models with standardized mortality rate (SMR)-weighting were used to compare time to virologic outcomes between the treated and EC groups. SMR-weighting was used to balance baseline age, CD4 cell count, VL, and ARV resistance genotype profiles between groups.

Results: The analysis included 76 treated and 65 EC individuals; covariate balance was achieved with SMR-weighting (absolute standardized difference ≤0.1 for all covariates). At 24 weeks, the likelihood of viral undetectability was doubled in the treated compared to the EC group (HR: 1.98 [95% CI: 1.02, 3.69]). Achievement of viral suppression was also more likely (1.28 [0.82, 2.06]). The likelihood of losing undetectability or suppression was higher in the EC group, although confidence intervals were wide (16.08 [3.99, 64.78] and 18.36 [2.48, 135.68], respectively) due to the limited number of outcomes in the treated group (loss of undetectability: 2/44, loss of suppression: 1/50).

Conclusions: In this first externally controlled trial of IBA effectiveness, IBA-containing regimens were associated with better virologic outcomes than non-IBA-containing regimens. However, the small number of covariates available in the trials limited the ability to control for confounding. With more individuals achieving and maintaining undetectability, IBA could have important clinical and public health implications for HTE individuals.