P-377. Efficacy and Safety by Age After Switch to Doravirine/Islatravir (100 mg/0.25 mg) Once Daily: Week 48 Results from Two Phase 3 Randomized, Active-Controlled Studies in Adults Living with HIV-1

TL;DR

A new once-daily HIV treatment called Doravirine/Islatravir was found to be effective and safe for adults, including those over 50 years old, after one year of use.

Contribution

This study provides evidence that Doravirine/Islatravir is a safe and effective treatment option for older adults with HIV.

Findings

Doravirine/Islatravir showed similar efficacy in suppressing HIV virus levels in both younger and older adults.

Safety and adverse event rates were comparable across age groups, including those over 65 years.

Weight changes were minimal and not clinically significant in any age subgroup.

Abstract

Doravirine/islatravir (DOR/ISL, 100 mg/0.25 mg) is an investigational once-daily regimen for HIV treatment. In two Phase 3 studies, switching to DOR/ISL was non-inferior for efficacy with a safety profile comparable to continuing baseline antiretroviral therapy (bART) or bictegravir/emtricitabine/tenofovir alafenamide (BIC/FTC/TAF) at Week 48 (W48). Because concerns about comorbidities and drug tolerability increase with age, this subgroup analysis evaluated the efficacy and safety of DOR/ISL by age.

Adults with HIV-1 RNA < 50 copies/mL receiving stable oral bART (MK-8591A-051 [P051]; NCT05631093) or BIC/FTC/TAF (MK-8591A-052 [P052]; NCT05630755) for ≥3 months were randomized (2:1) to switch to DOR/ISL (100 mg/0.25 mg) or to continue bART (P051) or BIC/FTC/TAF (P052). For P051+P052, efficacy results were pooled for both the DOR/ISL arms and the comparator arms (pooled comparator) and were summarized by age (< 50, ≥50 years) through W48. AEs and weight were reported by age subgroup for each study.

Across both studies, 708 participants switched to DOR/ISL and 356 continued bART or BIC/FTC/TAF (pooled comparator); overall 49.7% were ≥50 years old (10.6% ≥65 years). At W48, the proportion of DOR/ISL participants with HIV-1 RNA < 50 copies/mL was similar between those < 50 and ≥50 years in the pooled DOR/ISL group (92.1% vs 95.2%) and similar to the pooled comparator (94.5% vs 91.4%; Figure). Among DOR/ISL participants, rates of AEs, drug-related AEs, serious AEs, and discontinuations due to AEs were similar between age subgroups in both studies (Table). The AE profile was similar by treatment group for participants ≥65 years old. Rates of drug-related AEs were higher for open-label DOR/ISL than bART (P051), with a greater difference for participants ≥50 years, but were comparable between blinded treatment groups (P052). For DOR/ISL participants, weight changes were minimal overall (range of mean percent change in age subgroups −0.51% to 2.12%; Table). There were no clinically meaningful differences in weight change between those < 50 years and those ≥50 years.

At W48, switching to DOR/ISL (100 mg/0.25 mg) demonstrated high efficacy and was generally well tolerated across age subgroups in adults living with HIV-1, including those ≥50 years.

Pablo Tebas, MD, Merck: Honoraria|Shionogi: Honoraria|Viiv: Honoraria Frank A. Post, MD, PhD, Gilead: Grant/Research Support|Gilead: Honoraria|MSD: Grant/Research Support|MSD: Honoraria Moti Ramgopal, MD, FACP, FIDSA, AbbVie: Speaker Bureau|Gilead: Advisor/Consultant|Gilead: Honoraria|Shionogi Inc: Consultant|ViiV Healthcare: Advisor/Consultant|ViiV Healthcare: Honoraria Marcel Stoeckle, MD, Gilead: Advisor/Consultant|Gilead: Congress grants Andrew Carr, MD, Gilead: Board Member|Gilead: Grant/Research Support|Gilead: Honoraria|MSD: Board Member|MSD: Grant/Research Support|MSD: Honoraria|ViiV Healthcare: Board Member|ViiV Healthcare: Grant/Research Support|ViiV Healthcare: Honoraria Olayemi O. Osiyemi, MD, Gilead Sciences, Inc.: Advisor/Consultant|Gilead Sciences, Inc.: Honoraria|Merck: Advisor/Consultant|Merck: Honoraria|ViiV: Advisor/Consultant|ViiV: Honoraria Ronald G. Nahass, MD, Arbutus Pharma: Grant/Research Support|Insemed: Grant/Research Support|Janssen: Grant/Research Support|Merck: Grant/Research Support|VIR Pharma: Grant/Research Support Jason Szabo, MD, PhD, Gilead: Grant/Research Support|Gilead: Advisory board; Speaker fees|Merck: Speaker Fees|Novo Nordisk: Advisory board|ViiV: Grant/Research Support|ViiV: Advisory board; Speaker fees Anjana Grandhi, PhD, Merck & Co., Inc.: Employment|Merck & Co., Inc.: Stocks/Bonds (Public Company) Monica Fuszard, MS, Merck & Co.: Employment Stephanie O. Klopfer, PhD, Merck & Co., Inc: Employment|Merck & Co., Inc: Stocks/Bonds (Public Company) Rima Lahoulou, n/a, MSD: Employment|MSD: Stocks/Bonds (Private Company) Luisa M. Stamm, MD, PhD, Merck & Co., Inc.: Employment|Merck & Co., Inc.: Stocks/Bonds (Public Company) Michelle C. Fox, MD, Merck & Co., Inc.: Employment|Merck & Co., Inc.: Stocks/Bonds (Public Company) Jason Y. Kim, MD, MSCE, Merck & Co.: Employment|Merck & Co.: Stocks/Bonds (Public Company)

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