Phase 3
Completed N=672
Safety and Efficacy of a Switch to Doravirine/Islatravir in Participants With HIV-1 (MK-8591A-017)
HIV Infection
Source: ClinicalTrials.gov NCT04223778 ↗
Enrolled (actual)
672
Serious AEs
4.2%
Results posted
Sep 2022
Primary outcomePrimary: Percentage of Participants With Human Immunodeficiency Virus (HIV)-1 Ribonucleic Acid (RNA) ≥50 Copies/mL at Week 48 — 0.0; 1.5 Percentage of Participants — p=<.001
◆ Published Evidence
Established
27citations · ~14 / year
Switch to fixed-dose doravirine (100 mg) with islatravir (0·75 mg) once daily in virologically suppressed adults with HIV-1 on antiretroviral therapy: 48-week results of a phase 3, randomised, open-label, non-inferiority trial.
Summary
This study will evaluate the safety and efficacy of a switch to MK-8591A (a fixed dose combination of doravirine and islatravir) in human immunodeficiency virus -1 (HIV-1)-infected participants virologically suppressed on a protocol-specified antiretroviral regimen. The primary hypothesis is that a switch to MK-8591A will be non-inferior to continued treatment with baseline antiretroviral therapy (ART) as assessed by the percentage of participants with HIV-1 ribonucleic acid (RNA) ≥50 copies/mL at Week 48.
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 antiretroviral therapy: 48-week results of a phase 3, randomised, open-label, non-inferiority trial.
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Percentage of Participants With Human Immunodeficiency Virus (HIV)-1 Ribonucleic Acid (RNA) ≥50 Copies/mL at Week 48 |
0.0; 1.5 | <.001 sig |
| PRIMARY Percentage of Participants With One or More Adverse Events (AEs) up to Week 48 |
80.1; 70.2 | — |
| PRIMARY Percentage of Participants Who Discontinued Study Intervention Due to an AE up to Week 48 |
2.1; 0.3 | — |
| SECONDARY Percentage of Participants With HIV-1 RNA <40 or <50 Copies/mL at Week 48 |
94.6; 94.3; 95.2; 94.3 | — |
| SECONDARY Group 2 (Switch-Over): Percentage of Participants With HIV-1 RNA ≥50 Copies/mL, <40 Copies/mL or <50 Copies/mL at Week 96 |
0.9; 89.6; 89.6 | — |
| SECONDARY Group 1: Percentage of Participants With HIV-1 RNA ≥50 Copies/mL, <40 Copies/mL or <50 Copies/mL at Week 96 |
1.2; 86.0; 85.7 | — |
| SECONDARY Percentage Change From Baseline in CD4+ T-cell Count at Week 48 |
-0.7; 8.7 | — |
| SECONDARY Group 1: Percentage Change From Baseline in CD4+ T-cell Count at Week 96 |
4.49 | — |
| SECONDARY Group 1 & Group 2 (Switch-Over): Percentage Change From Week 48 in CD4+ T-cell Count at Week 96 |
5.29; 0.16 | — |
| SECONDARY Percentage of Participants With Evidence of Viral Drug Resistance-associated Substitutions at Week 48 |
0.0; 0.9 | — |
| SECONDARY Percentage of Participants With Evidence of Viral Drug Resistance-associated Substitutions at Week 96 |
0.0; 0.0 | — |
| SECONDARY Change From Baseline to Week 24 in Fasting Lipids in Participants on Protease Inhibitor (PI)-Containing Regimens (Including PI- and Integrase Strand Transferase Inhibitor [InSTI]-Containing Regimens) |
-12.94; 6.20; -0.97; 0.76; -7.47; 5.93 | — |
| SECONDARY Change From Baseline to Week 24 in Fasting Lipids in Participants on InSTI-based Regimens (Non-PI Containing Regimens) |
2.98; 8.74; 0.84; 0.27; 3.21; 8.50 | — |
| SECONDARY Change From Baseline to Week 24 in Fasting Lipids in Participants on All Other Non-PI- and Non-InSTI Containing Regimens |
7.18; 7.35; -3.43; -0.72; 11.33; 7.19 | — |
| SECONDARY Change From Baseline to Week 48 in Fasting Lipids in Participants on Protease Inhibitor (PI)-Containing Regimens (Including PI- and Integrase Strand Transferase Inhibitor [InSTI]-Containing Regimens) |
-15.31; 1.84; -1.45; -1.08; -8.59; 3.37 | 0.0094 sig |
| SECONDARY Change From Baseline to Week 48 in Fasting Lipids in Participants on InSTI-based Regimens (Non-PI Containing Regimens) |
2.23; 4.39; 0.23; 0.13; 2.74; 3.44 | 0.4093 |
| SECONDARY Change From Baseline to Week 48 in Fasting Lipids in Participants on All Other Non-PI- and Non-InSTI Containing Regimens |
5.66; 4.62; -3.84; -1.98; 9.27; 7.30 | — |
| SECONDARY Change From Baseline in Body Weight at Week 48 for InSTI-based Regimens (Non-PI-containing Regimens) |
0.66; 0.10 | — |
| SECONDARY Group 1: Percentage of Participants With One or More AEs up to Week 96 |
92.3 | — |
| SECONDARY Group 1: Percentage of Participants Who Discontinued Study Intervention Due to an AE up to Week 96 |
5.7 | — |
| SECONDARY Group 1 & Group 2 (Switch-Over): Percentage of Participants With One or More AEs From Week 48 to Week 96 |
73.0; 76.4 | — |
| SECONDARY Group 1 & Group 2 (Switch-Over): Percentage of Participants Who Discontinued Study Intervention Due to an AE From Week 48 to Week 96 |
3.7; 2.5 | — |
Eligibility Criteria
Inclusion Criteria
- Is human immunodeficiency virus (HIV-1) positive
- Has been receiving continuous, stable oral 2-drug or 3-drug combination (± pharmacokinetic (PK) booster) 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 she is 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 hypersensitivity or other contraindication to any of the components of the study interventions as determined by the investigator
- 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 taking long-acting cabotegravir-rilpivirine
- 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 (NCT04223778) 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.