Evaluating Diversity in Randomized Clinical Trials of Dolutegravir-Based Antiretroviral Therapy Regimens: Pooled 48-Week Analyses by Race, Sex, and Regional Subgroups

Abstract

Abstract Background In HIV clinical trials, proportions of Black and female participants achieving virologic suppression (VS) are often lower compared with White and male participants. As the antiretroviral therapy (ART) landscape continues to evolve, addressing existing challenges in clinical trial diversity will be critical to effectively translate results into clinical practice. Here, we pooled data to evaluate the efficacy and safety of dolutegravir (DTG)-containing regimens by race, sex, and regional subgroups. Methods Three pooled analyses were conducted using 48-week results from phase 3/3b trials: DTG 3-drug vs non-DTG-containing 3- or 4-drug regimens in ART-naive participants (ARIA, FLAMINGO, SINGLE, SPRING-2), DTG-containing 2-drug vs 3-drug regimens in ART-naive participants (GEMINI-1, GEMINI-2), and DTG 3-drug vs non-DTG-containing 3- or 4-drug regimens in ART-experienced participants (SAILING, DAWNING). Proportions of participants with VS, safety, and change from baseline in CD4+ cell count were analyzed. Results Proportions of participants achieving VS were high among those receiving DTG vs comparator regimens. Proportions of participants achieving VS were generally lower in Black (vs non-Black), female (vs male), and US (vs non-US) subgroups. No new safety signals emerged from any subgroup in pooled analyses. Conclusions These analyses confirm that, across subgroups, DTG has robust efficacy and a good safety profile at week 48 relative to comparator regimens. Achieving VS may vary by participant characteristics, highlighting the urgent need for enrollment to reflect the demographics of global HIV populations more accurately. Future studies should strive to support participants throughout the trial to ensure optimal representation, inclusion, and retention.