A Switch to Doravirine/Islatravir (DOR/ISL) in Participants With Human Immunodeficiency Virus Type 1 (HIV-1) Who Are Virologically Suppressed on Antiretroviral Therapy (ART) (MK-8591A-051)
Summary
The primary objectives of this study are to evaluate the safety and tolerability of a switch to Doravirine/Islatravir (DOR/ISL) compared with continued baseline antiretroviral therapy (ART), through Week 48; and to evaluate the antiretroviral activity of a switch to DOR/ISL compared with continued baseline ART at Week 48. The primary hypothesis is that DOR/ISL is non-inferior to continued baseline ART, as assessed by the percentage of participants with HIV-1 ribonucleic acid (RNA) ≥50 copies/mL at Week 48, with a margin of 4 percentage points used to define non-inferiority.
Timeline
- Start
- 2023-02-20
- Primary completion
- 2024-10-10
- Completion
- 2028-07-11
Outcome
Met primary endpoint
paper Doravirine and islatravir showed non-inferiority at week 48 PMID 41654374 ↗
registry analysis (non-inferiority test); Doravirine/Islatravir (DOR/ISL) vs Baseline ART + DOR/ISL; p <0.001; Estimated difference -3.58 (95% CI -7.81 to -0.77) NCT05631093 ↗
release “MK-8591A-051試験（非盲検試験）（アブストラクト#204B）の主要評価項目である48週時点のHIV-1 RNA量が50 copies/mL以上の被験者割合は、DOR/ISL群1.4%、bART群4.9%でした［群間差：-3.6%、95%信頼区間：-7.8, -0.8］。” msd.co.jp ↗
release “非盲検試験の051試験では、主要評価項目である48週時のHIV-1 RNA量が50 copies/mL以上の治験参加者の割合はIDVYNSO™切替え（n=366）で1%、ベースラインART継続群（n=185）で5%でした（群間差: -3.6%、95% CI, -7.8%, -0.8%）。” msd.co.jp ↗
Publications
- Diamond TL, Grandhi A, Fuszard M, Xu Y, Nwoke U, Zhang Y, Klopfer SO, Eves K, Benner J, Li M, Greaves W, Lahoulou R, Kim J, Fox MC, Asante-Appiah E. Switching to Daily Doravirine/Islatravir (100/0.25 mg) Maintains Viral Suppression Through Week 48 Despite Baseline Non-Nucleoside Reverse Transcriptase Inhibitor Resistance-Associated Mutations or M184I/V in Proviral DNA. J Infect Dis. 2026 May 29:jiag257. doi: 10.1093/infdis/jiag257. Online ahead of print.
- Orkin C, Mngqibisa R, Velez JD, Kumar P, Braun DL, Carr A, Bloch M, Walmsley S, Tebas P, Yokomaku Y, Diamond TL, Jackson B, Eves K, Grandhi A, Fuszard M, Klopfer SO, Stamm LM, Fox MC, Kim J. Switch to fixed-dose doravirine (100 mg) and islatravir (0.25 mg) once daily in virologically suppressed adults with HIV-1 on oral antiretroviral therapy: 48-week results of a phase 3, multicentre, randomised, open-label, non-inferiority trial. Lancet. 2026 Feb 7;407(10528):599-610. doi: 10.1016/S0140-6736(25)01945-2.
Drugs
| Evaluation | Drug | Modality | Dose | Route |
|---|---|---|---|---|
| Subject | Doravirine | Small molecule | 100 mg | Oral |
| Subject | Islatravir | Other / unclassified | 0.25 mg | Oral |