CROI 2025 Abstract eBook

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Oral Abstracts

204B Switch to DOR/ISL (100/0.25 mg) QD From Oral ART: An Open-Label Phase III Study in Adults With HIV-1 Michelle Fox 1 , Rosie Mngqibisa 2 , Juan Diego Velez 3 , Princy Kumar 4 , Dominique L. Braun 5 , Andrew Carr 6 , Mark Bloch 7 , Sharon Walmsley 8 , Pablo Tebas 9 , Anjana Grandhi 1 , Stephanie Klopfer 1 , Luisa Stamm 1 , Chloe Orkin 10 , Jason Kim 1 1 Merck & Co, Inc, Rahway, NJ, USA, 2 Enhancing Care Foundation, Durban, Canada, 3 Fundación Valle del Lili, Cali, Colombia, 4 Georgetown University Hospital, Washington, DC, USA, 5 University Hospital Zurich, Zurich, Switzerland, 6 St Vincent's Hospital, Sydney, Australia, 7 Holdsworth House Medical Group, Sydney, Australia, 8 University Health Network, Toronto, Canada, 9 University of Pennsylvania, Philadelphia, PA, USA, 10 Queen Mary University of London, London, UK Background: Doravirine (DOR), a NNRTI, and islatravir (ISL), an investigational nucleoside reverse transcriptase translocation inhibitor, have complementary mechanisms of action and resistance profiles. MK-8591A-051 is a phase 3 study evaluating the efficacy and safety of switching from oral ART to DOR/ISL (100/0.25 mg), a once-daily single-tablet regimen. Declines in CD4 and total lymphocyte counts were seen with higher ISL doses. Methods: In this open-label, non-inferiority study (NCT05631093), adults with HIV-1 RNA <50 c/mL for ≥3 months on oral 2- or 3-drug ART, with no history of treatment failure or known virologic resistance to DOR, were randomized 2:1 to switch to DOR/ISL (100/0.25 mg) or continue baseline ART (bART), stratified by bART regimen. Primary efficacy endpoint was % of participants with HIV-1 RNA ≥50 c/mL at week 48 (FDA Snapshot; non-inferiority margin 4%). Discontinuation was required for confirmed decline in total lymphocytes (≥30% and to <1.0x10 9 /L) or CD4 count (≥30% and to <350 cells/mm 3 from baseline ≥350 or to <200 from baseline ≤349). Results: We treated 551 participants: 366 switched to DOR/ISL and 185 continued bART. Mean age was 49.8 (±12.3) yrs; 39.7% were female at birth, 45.4% Black and 14.5% Latino. Median time since HIV diagnosis was 13.3 (IQR 7.2-20.4) yrs. bART was InSTI-based (64.2%), NNRTI-based (30.3%), or PI-based (5.4%) with median duration 3.8 (IQR 2.0-6.3) yrs. At week 48, HIV-1 RNA was ≥50 c/mL in 5 participants (1.4%) on DOR/ISL and 9 (4.9%) on bART (difference -3.6%, 95%CI -7.8, -0.8; CI upper bound <4%), demonstrating non-inferiority of DOR/ISL to bART. HIV-1 RNA was <50 c/mL in 95.6% on DOR/ISL and 91.9% on bART. Two participants who discontinued DOR/ISL due to viremia had resistance-associated mutations affecting susceptibility to all major classes except InSTIs that were also present in baseline proviral DNA. Drug-related adverse events (AEs) were more common with DOR/ISL (12.0%) vs bART (4.9%); none were serious and one (diarrhea) led to discontinuation. Other AE rates were similar for DOR/ISL and bART. At week 48, mean changes from baseline in CD4 T-cell and total lymphocyte counts were similar between the treatment arms. No participants discontinued treatment due to decreased CD4 T-cell or total lymphocyte count. Conclusions: Switching to DOR/ISL (100/0.25 mg) maintained viral suppression and was non-inferior to continuing bART at week 48. DOR/ISL was well tolerated with a similar safety profile to bART and did not adversely affect lymphocytes.

Oral Abstracts

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CROI 2025