Evaluating Diversity in Randomized Clinical Trials of Dolutegravir-Based Antiretroviral Therapy Regimens: Pooled 48-Week Analyses by Race, Sex, and Regional Subgroups. (24th June 2022)

• Record Type: Journal Article
• Authors: Rawlings, M Keith; Letang, Emilio; Quercia, Romina; Grove, Richard; DeMasi, Ralph; Min, Sherene; Vannappagari, Vani; Zolopa, Andrew; van Wyk, Jean; Smith, Kimberly
• Is Part Of: Open forum infectious diseases. Volume 9:Number 8(2022)
• Publication Date: 2022-06-24
• Subjects: dolutegravir -- pooled analysis -- integrase strand transfer inhibitor -- demographics -- regional analysis; Communicable diseases -- Periodicals; Medical microbiology -- Periodicals; Infection -- Periodicals; 616.9
• DOI: 10.1093/ofid/ofac304
• Languages: English
• ISSNs: 2328-8957

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. Abstract : In pooled analyses of dolutegravir trials, proportion of participants with HIV-1 RNA <50 copies/mL was lower in Black vs non-Black participants, female vs male participants, and US vs non-US participants, highlighting the importance of enrollment diversity in randomized clinical trials. Graphical Abstract: Graphical Abstract