Phase 3
Completed N=643
Switch to Doravirine/Islatravir (DOR/ISL) in Human Immunodeficiency Virus 1 (HIV-1) Participants Treated With Bictegravir/Emtricitabine/Tenofovir Alafenamide (BIC/FTC/TAF) (MK-8591A-018)
HIV Infection
Source: ClinicalTrials.gov NCT04223791 ↗
Enrolled (actual)
643
Serious AEs
3.2%
Results posted
Aug 2022
Primary outcomePrimary: Percentage of Participants With Human Immunodeficiency Virus 1 Ribonucleic Acid (HIV-1 RNA) ≥50 Copies/mL at Week 48 — 0.6; 0.3; 5.6; 5.3 Percentage of Participants — p=<.001
◆ Published Evidence
Established
23citations · ~12 / year
Switch to fixed-dose doravirine (100 mg) with islatravir (0·75 mg) once daily in virologically suppressed adults with HIV-1 on bictegravir, emtricitabine, and tenofovir alafenamide: 48-week results of a phase 3, randomised, controlled, double-blind, non-inferiority trial.
Summary
This study will evaluate the safety and efficacy of a switch to Doravirine/Islatravir (DOR/ISL) (MK-8591A) (a fixed dose combination of doravirine 100 mg and islatravir 0.75 mg) in participants living with human immunodeficiency virus-1 (HIV-1) virologically suppressed on a regimen of bictegravir/emtricitabine/tenofovir alafenamide (BIC/FTC/TAF). The primary hypothesis is that a switch to DOR/ISL (MK-8591A) will be non-inferior to continued treatment with BIC/FTC/TAF as assessed by the proportion of participants with HIV-1 ribonucleic acid (RNA) ≥50 copies/mL at Week 48. Participants who benefit from their assigned intervention (as determined by investigator) will be able to continue treatment through a 24-week study extension.
Linked Publications
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Switch to fixed-dose doravirine (100 mg) with islatravir (0·75 mg) once daily in virologically suppressed adults with HIV-1 on bictegravir, emtricitabine, and tenofovir alafenamide: 48-week results of a phase 3, randomised, controlled, double-blind, non-inferiority trial.
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Percentage of Participants With Human Immunodeficiency Virus 1 Ribonucleic Acid (HIV-1 RNA) ≥50 Copies/mL at Week 48 |
0.6; 0.3; 5.6; 5.3; 93.8; 94.4 | <.001 sig |
| PRIMARY Percentage of Participants With One or More Adverse Events (AEs) up to Week 48 |
71.1; 74.6 | — |
| PRIMARY Percentage of Participants Who Discontinued Study Intervention Due to an AE up to Week 48 |
2.5; 2.5 | — |
| SECONDARY Percentage of Participants With HIV-1 RNA ≥50 Copies/mL at Week 96 |
0.6; 0.3; 14.3; 8.8; 85.1; 90.9 | <0.001 sig |
| SECONDARY Percentage of Participants With HIV-1 RNA ≥50 Copies/mL at Week 144 |
0.9; 1.3; 47.2; 33.2; 51.9; 65.5 | — |
| SECONDARY Percentage of Participants With HIV-1 RNA <50 Copies/mL at Week 48 |
93.8; 94.4; 5.6; 5.3; 0.6; 0.3 | — |
| SECONDARY Percentage of Participants With HIV-1 RNA <40 Copies/mL at Week 48 |
93.2; 94.0 | — |
| SECONDARY Percentage of Participants With HIV-1 RNA <50 Copies/mL at Week 96 |
85.1; 90.9; 14.3; 8.8; 0.6; 0.3 | — |
| SECONDARY Percentage of Participants With HIV-1 RNA <40 Copies/mL at Week 96 |
84.8; 90.9 | — |
| SECONDARY Percentage of Participants With HIV-1 RNA <50 Copies/mL at Week 144 |
51.9; 65.5; 47.2; 33.2; 0.9; 1.3 | — |
| SECONDARY Percentage of Participants With HIV-1 RNA <40 Copies/mL at Week 144 |
51.9; 65.5 | — |
| SECONDARY Mean Change From Baseline in Cluster of Differentiation-positive (CD4+) T-cell Count at Week 48 |
-19.66; 40.51 | — |
| SECONDARY Mean Change From Baseline in CD4+ T-cell Count at Week 96 |
5.36; 62.67 | — |
| SECONDARY Mean Change From Baseline in CD4+ T-cell Count at Week 144 |
0.48; 66.25 | — |
| SECONDARY Number of Participants With Viral Drug Resistance-associated Substitutions at Week 48 |
— | — |
| SECONDARY Number of Participants With Evidence of Viral Drug Resistance-associated Substitutions at Week 96 |
— | — |
| SECONDARY Number of Participants With Evidence of Viral Drug Resistance-associated Substitutions at Week 144 |
— | — |
| SECONDARY Change From Baseline in Body Weight at Week 48 |
0.23; 0.55 | 0.392 |
| SECONDARY Change From Baseline in Body Weight at Week 96 |
0.29; 0.72 | 0.3263 |
| SECONDARY Change From Baseline in Body Weight at Week 144 |
0.63; 0.84 | — |
| SECONDARY Percentage of Participants With One or More AEs |
96.3; 94.4 | — |
| SECONDARY Percentage of Participants Who Discontinued Study Intervention Due to an AE |
22.0; 6.9 | — |
Eligibility Criteria
Inclusion Criteria
- Is HIV-1 positive with plasma Human Immunodeficiency Virus 1 (HIV-1) RNA <50 copies/mL at screening.
- Has been receiving bictegravir/emtricitabine/tenofovir alafenamide (BIC/FTC/TAF) therapy with documented viral suppression (HIV-1 RNA <50 copies/mL) for ≥3 months prior to signing informed consent and has no history of prior virologic treatment failure on any past or current regimen.
- Females are eligible to participate if not pregnant or breastfeeding, and at least one of the following conditions applies: Is not a woman of childbearing potential (WOCBP); is a WOCBP and using an acceptable contraceptive method, or be abstinent from heterosexual intercourse as their preferred and usual lifestyle; a WOCBP must have a negative highly sensitive pregnancy test ([urine or serum] as required by local regulations) within 24 hours before the first dose of study intervention; if a urine test cannot be confirmed as negative (e.g. an ambiguous result), a serum pregnancy test is required. In such cases, the participant must be excluded from participation if the serum pregnancy result is positive.
Exclusion Criteria
- Has HIV-2 infection.
- Has an active diagnosis of hepatitis due to any cause, including active Hepatitis B Virus (HBV) co-infection.
- Has a history of malignancy ≤5 years prior to signing informed consent except for adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer, or cutaneous Kaposi's sarcoma.
- Is taking or is anticipated to require systemic immunosuppressive therapy, immune modulators, or any prohibited therapies.
- Is currently participating in or has participated in a clinical study with an investigational compound or device from 45 days prior to Day 1 through the study treatment period.
- Has a documented or known virologic resistance to doravirine (DOR).
- expects to conceive or donate eggs at any time during the study.
Data sourced from ClinicalTrials.gov (NCT04223791) and the linked publication. Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication. Informational only — not medical advice.