A Switch to Doravirine/Islatravir (DOR/ISL) in Participants With Human Immunodeficiency Virus Type 1 (HIV-1) Who Are Virologically Suppressed on Bictegravir/Emtricitabine/Tenofovir Alafenamide (BIC/FTC/TAF) (MK-8591A-052)
Summary
The primary objectives of this study are to evaluate the antiretroviral activity of a switch to Doravirine/Islatravir (DOR/ISL) compared with continued Bictegravir/Emtricitabine/Tenofovir Alafenamide (BIC/FTC/TAF) at Week 48; and to evaluate the safety and tolerability of a switch to DOR/ISL compared with continued BIC/FTC/TAF, through Week 48. The primary hypotheses are that (1) DOR/ISL is non-inferior to continued BIC/FTC/TAF, 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; and (2) DOR/ISL is superior to BIC/FTC/TAF, as assessed by the percentage of participants with HIV-1 RNA ≥50 copies/mL at Week 48.
Timeline
- Start
- 2023-02-17
- Primary completion
- 2024-10-25
- Completion
- 2028-08-04
Outcome
Met primary endpoint
registry analysis (non-inferiority test); DOR/ISL and Placebo to BIC/FTC/TAF vs BIC/FTC/TAF and Placebo to DOR/ISL; p = 0.003; Risk Difference (RD) 0.88 (95% CI -1.86 to 2.90); Miettinen and Nurminen method NCT05630755 ↗
paper At week 48, doravirine and islatravir showed non-inferiority to bictegravir, emtricitabine, and tenofovir alafenamide PMID 41654375 ↗
release “which showed that the investigational two-drug regimen of DOR/ISL maintained viral suppression and demonstrated non-inferiority to the three-drug regimen BIC/FTC/TAF in MK-8591A-052” merck.com ↗
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.
- Colson AE, Mills AM, Ramgopal MN, Bettacchi C, Osiyemi OO, Hinestrosa F, Crofoot G, Katner HP, Gatanaga H, Johnson M, Diamond TL, Barninger E, Eves K, Su FH, Xu Y, Klopfer SO, Stamm LM, Fox MC, Lahoulou R. Switch to fixed-dose doravirine (100 mg) and islatravir (0.25 mg) once daily in virologically suppressed adults with HIV-1 on bictegravir, emtricitabine, and tenofovir alafenamide: 48-week results of a phase 3, multicentre, randomised, controlled, double-blind, non-inferiority trial. Lancet. 2026 Feb 7;407(10528):611-621. doi: 10.1016/S0140-6736(25)01948-8.
Drugs
| Evaluation | Drug | Modality | Dose | Route |
|---|---|---|---|---|
| Subject | Bictegravir | Small molecule | 50 mg | Oral |
| Subject | Doravirine | Small molecule | 100 mg | Oral |
| Subject | Islatravir | Other / unclassified | 0.25 mg | Oral |
| Subject | emtricitabine | Other / unclassified | 200 mg | Oral |
| Subject | tenofovir alafenamide | Small molecule | 25 mg | Oral |