HIV-1 InfectionPhase 3NCT05631093
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)
A Phase 3 study testing ART and DOR/ISL in people with HIV-1 Infection, run by Merck Sharp & Dohme LLC at 53 sites in 8 countries.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- HIV-1 Infection
- What is being tested?
- ART and DOR/ISL
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 553 participants
- Where
- 53 sitesin 8 countries
- Study dates
- 20 Feb 2023to 11 Jul 2028
- Phase
- Phase 3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Is Human Immunodeficiency Virus-1 (HIV-1) positive with plasma HIV-1 Ribonucleic Acid (RNA) <50 copies/mL at screening
- Has been receiving continuous, stable oral 2-drug or 3-drug combination (± PK booster) antiretroviral therapy ART with documented viral suppression (HIV-1 RNA <50 copies/mL) for ≥3 consecutive months prior to providing documented informed consent and has no history of prior virologic treatment failure on any past or current regimen
- Female is not a participant of childbearing potential (POCBP); or if a POCBP uses an acceptable contraceptive method or abstains from penile-vaginal intercourse as their preferred and usual lifestyle; has a negative highly sensitive pregnancy test; and whose medical history, menstrual history, and recent sexual activity has been reviewed by the investigator
Who cannot join
- Has HIV-2 infection
- Has hypersensitivity or other contraindication to any of the components of the study interventions as determined by the investigator
- Has a diagnosis of an active acquired immunodeficiency syndrome (AIDS)-defining opportunistic infection within 30 days prior to screening
- Has active hepatitis B virus (HBV) infection
- Has chronic hepatitis C virus (HCV) infection consistent with cirrhosis
- Has a ≤5 years prior history of malignancy
Show all 10Show fewer
- Is taking or is anticipated to require systemic immunosuppressive therapy, immune modulators, or strong and moderate cytochrome P450 3A (CYP3A) inducers
- Has taken long-acting HIV therapy at any time
- Is currently participating in or has participated in a clinical study and received (or is receiving) 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 Doravine (DOR)
Trial locations and contacts
53 sites in 8 countries.
53 sites in 8 countries
United States15 sites
Central Texas Clinical Research ( Site 3015)
Austin, Texas, 78705
Infectious Disease Specialists of Atlanta ( Site 3003)
Decatur, Georgia, 30033
Midway Immunology and Research Center ( Site 3009)
Ft. Pierce, Florida, 34982
ID Care ( Site 3041)
Hillsborough, New Jersey, 08844
The Crofoot Research Center ( Site 3040)
Houston, Texas, 77098
DCOL Center for Clinical Research ( Site 3022)
Longview, Texas, 75605
Kaiser Permanente-Infectious Disease ( Site 3014)
Los Angeles, California, 90027
Orlando Immunology Center ( Site 3004)
Orlando, Florida, 32803
Palmtree Clinical Research ( Site 3032)
Palm Springs, California, 92262
Penn Medicine: University of Pennsylvania Health System-Perelman Center for Advanced Medicine ( Site
Philadelphia, Pennsylvania, 19104
Zuckerberg San Francisco General Hospital and Trauma Center-UCSF ID Clinical Trials Center ( Site 30
San Francisco, California, 94110
CAN Community Health - Sarasota ( Site 3017)
Sarasota, Florida, 34237
Chatham County Health Department - Chatham CARE Center-Infectious Disease ( Site 3028)
Savannah, Georgia, 31401
Georgetown University Medical Center ( Site 3006)
Washington D.C., District of Columbia, 20007
Triple O Research Institute, P.A ( Site 3026)
West Palm Beach, Florida, 33407
South Africa9 sites
Josha Research ( Site 3903)
Bloemfontein, Free State, 9300
Family Clinical Research Unit (Fam-Cru)-Adult Infectious Diseases ( Site 3908)
Cape Town, Western Cape, 7505
Desmond Tutu Health Foundation ( Site 3902)
Cape Town, Western Cape, 7925
Wentworth Hospital ( Site 3904)
Durban, KwaZulu-Natal, 4052
Perinatal HIV Research Unit (PHRU)-Adult Treatment and Research ( Site 3905)
Johannesburg, Gauteng, 2013
Helen Joseph Hospital ( Site 3910)
Johannesburg, Gauteng, 2092
Ezintsha-Clinical Research Site ( Site 3907)
Johannesburg, Gauteng, 2193
Be Part Yoluntu Centre ( Site 3901)
Paarl, Western Cape, 7646
Private Practice Dr. Marleen de Jager ( Site 3900)
Pretoria, Gauteng, 0007
United Kingdom7 sites
Heartlands Hospital ( Site 4102)
Birmingham, B9 5SS
North Manchester General Hospital ( Site 4107)
Crumpsall, England, M8 5RB
Brighton and Sussex University Hospitals NHS Trust ( Site 4104)
East Sussex, Brighton And Hove, BN2 1ES
Royal London Hospital ( Site 4100)
London, England, E1 1BB
Royal Free Hospital ( Site 4101)
London, England, NW32QG
King's College Hospital ( Site 4108)
London, London, City of, SE5 9RL
Royal Victoria Infirmary ( Site 4105)
Newcastle upon Tyne, England, NE1 4LP
Switzerland6 sites
University Hospital Basel-Infectiology ( Site 4002)
Basel, Canton of Basel-City, 4031
Inselspital Bern-Inselspital Infektiologie ( Site 4003)
Bern, 3010
Hôpitaux Universitaires de Genève (HUG)-Infectious Disease Department ( Site 4004)
Geneva, Canton of Geneva, 1211
CHUV (centre hospitalier universitaire vaudois) ( Site 4006)
Lausanne, Canton of Vaud, 1011
Ospedale Regionale di Lugano, Sede Civico-Servizio Malattie Infettive ( Site 4005)
Lugano, Canton Ticino, 6903
UniversitätsSpital Zürich ( Site 4000)
Zurich, Canton of Zurich, 8091
Australia5 sites
Holdsworth House Medical Practice - Brisbane ( Site 4201)
Brisbane, Queensland, 4006
Royal Brisbane and Women's Hospital-Infectious Diseases Research ( Site 4204)
Brisbane, Queensland, 4029
Holdsworth House Medical Practice ( Site 4200)
Darlinghurst, New South Wales, 2010
Prahran Market Clinic ( Site 4202)
Melbourne, Victoria, 3181
St Vincent's Hospital-IBAC ( Site 4203)
Sydney, New South Wales, 2010
Canada5 sites
Hamilton Health Sciences- Urgent Care Centre-SIS Clinic ( Site 3104)
Hamilton, Ontario, L8S 1A4
Clinique de médecine Urbaine du Quartier Latin ( Site 3101)
Montreal, Quebec, H2L 4E9
Clinique Medicale lActuel-Clinical Research ( Site 3100)
Montreal, Quebec, H2L 4P9
Maple Leaf Research ( Site 3103)
Toronto, Ontario, M5G 1K2
Toronto General Hospital ( Site 3102)
Toronto, Ontario, M5G 2M1
Colombia3 sites
Ciensalud Ips S A S ( Site 3300)
Barranquilla, Atlántico, 08001
Clinica de la Costa S.A.S. ( Site 3305)
Barranquilla, Atlántico, 080020
Fundacion Valle del Lili- CIC ( Site 3302)
Cali, Valle del Cauca Department, 760032
Japan3 sites
National Hospital Organization Nagoya Medical Center ( Site 4403)
Nagoya, Aichi-ken, 460-0001
Tokyo Medical University Hospital ( Site 4404)
Shinjuku-ku, Tokyo, 160-0023
Center Hospital of the National Center for Global Health and Medicine ( Site 4401)
Shinjyuku-ku, Tokyo, 162-8655
About this study
Official title: A Phase 3, Randomized, Active-Controlled, Open-Label Clinical Study to Evaluate a Switch to Doravirine/Islatravir (DOR/ISL 100 mg/0.25 mg) Once-Daily in Participants With HIV-1 Who Are Virologically Suppressed on Antiretroviral Therapy
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.
- Conditions
- HIV-1 Infection
- Being tested
- ART, DOR/ISL
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ARTDrug
Standard of care ART, per approved product list, taken orally
DOR/ISLDrug
Also called MK-8591A
Single tablet combination of 100 mg doravirine (DOR) with 0.25 mg Islatravir (ISL) in tablet form, taken orally, once daily.
| Study group | Role | What they receive |
|---|---|---|
| DOR/ISL | Experimental | Participants with Human Immunodeficiency Virus-1 (HIV-1) that have been virologically suppressed for ≥3 consecutive months who were previously treated with continuous baseline antiretroviral therapy (ART) receive doravine/islatravir (DOR/ISL), a fixed dose combination (FDC) of 100 mg DOR/0.25 mg ISL orally once daily (qd) for 144 weeks. At Week 144, participants who consent to enter the optional study extension will continue to receive DOR/ISL qd (100 mg/0.25 mg) for an additional 96 weeks or until it is commercially accessible (whichever comes first). Receives: Drug: DOR/ISL |
| ART + DOR/ISL | Active comparator | Participants with HIV-1 that has been virologically suppressed for ≥3 consecutive months who were previously treated with continuous baseline ART received standard of care (SOC) ART for 48 weeks, followed by treatment with DOR/ISL as a FDC of 100 mg DOR/0.25 mg ISL orally qd until Week 144. At Week 144, participants who consent to enter the optional study extension will continue to receive DOR/ISL qd (100 mg/0.25 mg) for an additional 96 weeks or until it is commercially accessible (whichever comes first). Receives: Drug: ART |
What is being measured
The primary outcome is the main question the study is designed to answer.
Percentage of Participants With HIV-1 RNA ≥50 Copies/mL at Week 48
HIV-1 RNA levels in plasma were measured by polymerase chain reaction (PCR) assay with a reliable lower limit of quantification of <50 copies/mL. The percentage of participants with HIV-1 RNA ≥50 copies/mL at Week 48 is presented using the FDA Snapshot missing data approach.
Measured: Week 48
Percentage of Participants With One or More Adverse Events (AEs) at Week 48
An AE is defined as any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. The percentage of participants who experienced at least one AE from Day 1 up to Week 48 are reported.
Measured: Up to Week 48
Percentage of Participants With an AE Leading to Discontinuation of Study Intervention at Week 48
An AE is defined as any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. The percentage of participants who experienced at least one AE leading to discontinuation of study intervention from Day 1 up to Week 48 are reported.
Measured: Up to Week 48
Secondary outcomes (24)
Percentage of Participants With HIV-1 RNA <200 Copies/mL at Week 48
HIV-1 RNA levels in plasma were measured by a polymerase chain reaction (PCR) assay with a reliable lower limit of quantification of <50 copies/mL. The percentage of participants with HIV-1 RNA <200 copies/mL at Week 48 is presented using the FDA Snapshot missing data approach.
Measured: Week 48
Percentage of Participants With HIV-1 RNA <50 Copies/mL at Week 48
HIV-1 RNA levels in plasma were measured by a polymerase chain reaction (PCR) assay with a reliable lower limit of quantification of <50 copies/mL. The percentage of participants with HIV-1 RNA <50 copies/mL at Week 48 is presented using the FDA Snapshot missing data approach.
Measured: Week 48
Percentage of Participants With HIV-1 RNA <200 Copies/mL at Week 96
HIV-1 RNA levels in plasma were measured by a polymerase chain reaction (PCR) assay with a reliable lower limit of quantification of <50 copies/mL. The percentage of participants with HIV-1 RNA <200 copies/mL at Week 96 is presented using the FDA Snapshot missing data approach.
Measured: Week 96
Participants With HIV-1 RNA <200 Copies/mL at Week 144
HIV-1 RNA levels in plasma were measured by a polymerase chain reaction (PCR) assay with a reliable lower limit of quantification of <50 copies/mL. The percentage of participants with HIV-1 RNA <200 copies/mL at Week 144 is presented using the FDA Snapshot missing data approach.
Measured: Week 144
Percentage of Participants With HIV-1 RNA ≥50 Copies/mL at Week 96
HIV-1 RNA levels in plasma were measured by a polymerase chain reaction (PCR) assay with a reliable lower limit of quantification of <50 copies/mL. The percentage of participants with HIV-1 RNA ≥50 copies/mL at Week 96 is presented using the FDA Snapshot missing data approach.
Measured: Week 96
Percentage of Participants With HIV-1 RNA ≥50 Copies/mL at Week 144
HIV-1 RNA levels in plasma were measured by a polymerase chain reaction (PCR) assay with a reliable lower limit of quantification of <50 copies/mL. The percentage of participants with HIV-1 RNA ≥50 copies/mL at Week 144 is presented using the FDA Snapshot missing data approach.
Measured: Week 144
Percentage of Participants With HIV-1 RNA <50 Copies/mL at Week 96
HIV-1 RNA levels in plasma were measured by a polymerase chain reaction (PCR) assay with a reliable lower limit of quantification of <50 copies/mL. The percentage of participants with HIV-1 RNA <50 copies/mL at Week 96 is presented using the FDA Snapshot missing data approach.
Measured: Week 96
Percentage of Participants With HIV-1 RNA <50 Copies/mL at Week 144
HIV-1 RNA levels in plasma were measured by a polymerase chain reaction (PCR) assay with a reliable lower limit of quantification of <50 copies/mL. The percentage of participants with HIV-1 RNA <50 copies/mL at Week 144 is presented using the FDA Snapshot missing data approach.
Measured: Week 144
Mean Change of Plasma Cluster of Differentiation 4 (CD4+) T-Cell Count From Baseline Day 1 to Week 48
Plasma CD4+ T-Cell Count was measured in cells/mm^3 for baseline and 48 weeks. Baseline measurements were defined as the Day 1 value of each participant. The mean change of plasma CD4+ T-Cell count from baseline to Week 48 is presented.
Measured: Baseline at Day 1 and Week 48
Mean Change of Plasma CD4+ T-Cell Count From Baseline Week 48 to Week 96
Mean change from baseline at Week 48 in CD4+ T-cell count at Week 96. This outcome measure is applicable to participants who were randomized to switch to DOR/ISL at Week 48.
Measured: Baseline at Week 48 and Week 96
Mean Change of Plasma CD4+ T-Cell Count From Baseline Day 48 to Week 144
Mean change from baseline at Week 48 in CD4+ T-cell count at Week 144. This outcome measure is applicable to participants who were randomized to switch to DOR/ISL at Week 48.
Measured: Baseline at Week 48 and Week 144
Mean Change of Plasma CD4+ T-Cell Count From Baseline Day 1 to Week 96
Mean change from baseline at Day 1 in CD4+ T-cell count at Week 96. This outcome measure is applicable to those randomized to start DOR/ISL on Day 1.
Measured: Baseline at Day 1 and Week 96
Mean Change of Plasma CD4+ T-Cell Count From Baseline Day 1 to Week 144
Mean change from baseline at Day 1 in CD4+ T-cell count at Week 144. This outcome measure is applicable to those randomized to start DOR/ISL on Day 1.
Measured: Baseline at Day 1 and Week 144
Percentage of Participants With Treatment-Emergent, Resistance-associated Substitutions at Week 48
Participants with clinically significant confirmed viremia [2 consecutive occurences 4 weeks (+-1 week) apart of HIV-1 RNA >=200 copies/mL at any time during the study] or who discontinue study intervention for another reason with HIV-1 RNA >=200 copies/mL at the time of discontinuation met the criteria for post-baseline resistance testing. Participants with HIV-1 RNA >=400 copies/mL or any participant for whom available genotypic or phenotypic data show evidence of resistance, irrespective of viral load were included in the resistance analysis subset. Plasma samples were collected for genotypic and phenotypic HIV-1 viral drug resistance testing and used to assess resistance-associated substitutions and virus susceptibility to study intervention. The percentage of participants in the resistance analysis subset with treatment-emergent resistance-associated substitutions to the study intervention is presented.
Measured: Up to Week 48
Mean Change From Baseline in Fasting Low Density Lipoprotein Cholesterol (LDL-C) at Week 48
Blood serum samples were taken at baseline and Week 48. The mean change from baseline in fasting Low density lipoprotein cholesterol (LDL-C) at Week 48 is presented for PI-containing regimens (including PI- + InSTI-containing regimens), non-PI- and non-InSTI-containing regimens, and InSTI-containing regimens (non-PI-containing regimens) are presented.
Measured: Baseline and Week 48
Mean Change From Baseline in Fasting Non-High Density Lipoprotein Cholesterol (Non-HDL-C) at Week 48
Blood serum samples were taken at baseline and Week 48. The mean change from baseline in fasting Non-HDL-C at Week 48 is presented for PI-containing regimens (including PI- + InSTI-containing regimens), non-PI- and non-InSTI-containing regimens, and InSTI-containing regimens (non-PI-containing regimens) are presented.
Measured: Baseline and Week 48
Participants With One or More AEs at Week 96
An AE is defined as any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. The percentage of participants who experienced at least one AE from Day 1 up to Week 96 is reported.
Measured: Up to Week 96
Participants With One or More AEs at Week 144
An AE is defined as any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. The percentage of participants who experienced at least one AE from Day 1 up to Week 144 is reported.
Measured: Up to Week 144
Percentage of Participants With AEs Leading to Discontinuation of Study Intervention at Week 96
An AE is defined as any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. The percentage of participants who experienced at least one AE leading to discontinuation of study intervention from Day 1 up to Week 96 are reported.
Measured: Up to Week 96
Percentage of Participants With AEs Leading to Discontinuation of Study Intervention at Week 144
An AE is defined as any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. The percentage of participants who experienced at least one AE leading to discontinuation of study intervention from Day 1 up to Week 144 are reported.
Measured: Up to Week 144
Percentage of Participants With One or More AEs From Week 48 up to Week 96
An AE is defined as any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. The percentage of participants who experienced at least one AE from Week 48 up to Week 96 is reported.
Measured: Week 48 up to Week 96
Percentage of Participants With One or More AEs From Week 48 up to Week 144
An AE is defined as any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. The percentage of participants who experienced at least one AE from Week 48 up to Week 144 is presented.
Measured: Week 48 up to Week 144
Percentage of Participants With AEs Leading to Discontinuation of Study Intervention From Week 48 up to Week 96
An AE is defined as any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. The percentage of participants who experienced at least one AE leading to discontinuation of study intervention from Week 48 up to Week 96 are reported.
Measured: Week 48 up to Week 96
Percentage of Participants With AEs Leading to Discontinuation of Study Intervention From Week 48 up to Week 144
An AE is defined as any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. The percentage of participants who experienced at least one AE leading to discontinuation of study intervention from Week 48 up to Week 144 are reported.
Measured: Week 48 up to Week 144
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted30 Nov 2022
- Study start20 Feb 2023
- Primary completion10 Oct 2024
- Study completion11 Jul 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for HIV-1 InfectionStudies of the same condition, open and under way.
- More trials run by Merck Sharp & Dohme LLCThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 553 participants (actual)
Sponsor and investigators
- Lead sponsor
- Merck Sharp & Dohme LLC
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Medical Director, Study director, Merck Sharp & Dohme LLC
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05631093
- Sponsor's protocol ID
- 8591A-051
- Other IDs
- MK-8591A-051, jRCT2031220698, U1111-1283-3894, 2022-502127-22-00, 2022-502127-22
- Status last verified
- Nov 2025
- First submitted
- 18 Nov 2022
- Last updated
- 21 Nov 2025
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: https://trialstransparency.msdclinicaltrials.com/pdf/ProcedureAccessClinicalTrialData.pdf
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.
PubMed 42213454Orkin 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.
PubMed 41654374
Study at a glance
From the registry record, last updated by the sponsor on 21 Nov 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 3, Randomized, Active-Controlled, Open-Label Clinical Study to Evaluate a Switch to Doravirine/Islatravir (DOR/ISL 100 mg/0.25 mg) Once-Daily in Participants With HIV-1 Who Are Virologically Suppressed on Antiretroviral Therapy
- ClinicalTrials.gov ID
- NCT05631093
- Acronym / sponsor ID
- 8591A-051
- Conditions
- HIV-1 Infection
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 553 participants (actual)
- Lead sponsor
- Merck Sharp & Dohme LLCIndustry (pharma, biotech, devices)
- Study start
- 20 Feb 2023 (actual)
- Primary completion
- 10 Oct 2024 (actual)
- Study completion
- 11 Jul 2028 (estimated)
- First posted
- 30 Nov 2022 (actual)
- Results
- Posted 21 Nov 2025
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| DOR/ISL | Experimental | Drug: DOR/ISLParticipants with Human Immunodeficiency Virus-1 (HIV-1) that have been virologically suppressed for ≥3 consecutive months who were previously treated with continuous baseline antiretroviral therapy (ART) receive doravine/islatravir (DOR/ISL), a fixed dose combination (FDC) of 100 mg DOR/0.25 mg ISL orally once daily (qd) for 144 weeks. At Week 144, participants who consent to enter the optional study extension will continue to receive DOR/ISL qd (100 mg/0.25 mg) for an additional 96 weeks or until it is commercially accessible (whichever comes first). |
| ART + DOR/ISL | Active comparator | Drug: ARTParticipants with HIV-1 that has been virologically suppressed for ≥3 consecutive months who were previously treated with continuous baseline ART received standard of care (SOC) ART for 48 weeks, followed by treatment with DOR/ISL as a FDC of 100 mg DOR/0.25 mg ISL orally qd until Week 144. At Week 144, participants who consent to enter the optional study extension will continue to receive DOR/ISL qd (100 mg/0.25 mg) for an additional 96 weeks or until it is commercially accessible (whichever comes first). |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- Is Human Immunodeficiency Virus-1 (HIV-1) positive with plasma HIV-1 Ribonucleic Acid (RNA) <50 copies/mL at screening
- Has been receiving continuous, stable oral 2-drug or 3-drug combination (± PK booster) antiretroviral therapy ART with documented viral suppression (HIV-1 RNA <50 copies/mL) for ≥3 consecutive months prior to providing documented informed consent and has no history of prior virologic treatment failure on any past or current regimen
- Female is not a participant of childbearing potential (POCBP); or if a POCBP uses an acceptable contraceptive method or abstains from penile-vaginal intercourse as their preferred and usual lifestyle; has a negative highly sensitive pregnancy test; and whose medical history, menstrual history, and recent sexual activity has been reviewed by the investigator
Key exclusion criteria (10 listed)
- Has HIV-2 infection
- Has hypersensitivity or other contraindication to any of the components of the study interventions as determined by the investigator
- Has a diagnosis of an active acquired immunodeficiency syndrome (AIDS)-defining opportunistic infection within 30 days prior to screening
- Has active hepatitis B virus (HBV) infection
- Has chronic hepatitis C virus (HCV) infection consistent with cirrhosis
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| ARTStandard of care ART, per approved product list, taken orally | Drug | ART + DOR/ISL |
| DOR/ISLAlso: MK-8591ASingle tablet combination of 100 mg doravirine (DOR) with 0.25 mg Islatravir (ISL) in tablet form, taken orally, once daily. | Drug | DOR/ISL |
Primary outcome
Percentage of Participants With HIV-1 RNA ≥50 Copies/mL at Week 48
Time frame: Week 48
HIV-1 RNA levels in plasma were measured by polymerase chain reaction (PCR) assay with a reliable lower limit of quantification of <50 copies/mL. The percentage of participants with HIV-1 RNA ≥50 copies/mL at Week 48 is presented using the FDA Snapshot missing data approach.
Percentage of Participants With One or More Adverse Events (AEs) at Week 48
Time frame: Up to Week 48
An AE is defined as any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. The percentage of participants who experienced at least one AE from Day 1 up to Week 48 are reported.
Percentage of Participants With an AE Leading to Discontinuation of Study Intervention at Week 48
Time frame: Up to Week 48
An AE is defined as any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. The percentage of participants who experienced at least one AE leading to discontinuation of study intervention from Day 1 up to Week 48 are reported.
24 secondary outcomes
Percentage of Participants With HIV-1 RNA <200 Copies/mL at Week 48
Time frame: Week 48
Percentage of Participants With HIV-1 RNA <50 Copies/mL at Week 48
Time frame: Week 48
Percentage of Participants With HIV-1 RNA <200 Copies/mL at Week 96
Time frame: Week 96
Participants With HIV-1 RNA <200 Copies/mL at Week 144
Time frame: Week 144
Percentage of Participants With HIV-1 RNA ≥50 Copies/mL at Week 96
Time frame: Week 96
Percentage of Participants With HIV-1 RNA ≥50 Copies/mL at Week 144
Time frame: Week 144
Percentage of Participants With HIV-1 RNA <50 Copies/mL at Week 96
Time frame: Week 96
Percentage of Participants With HIV-1 RNA <50 Copies/mL at Week 144
Time frame: Week 144
Mean Change of Plasma Cluster of Differentiation 4 (CD4+) T-Cell Count From Baseline Day 1 to Week 48
Time frame: Baseline at Day 1 and Week 48
Mean Change of Plasma CD4+ T-Cell Count From Baseline Week 48 to Week 96
Time frame: Baseline at Week 48 and Week 96
Mean Change of Plasma CD4+ T-Cell Count From Baseline Day 48 to Week 144
Time frame: Baseline at Week 48 and Week 144
Mean Change of Plasma CD4+ T-Cell Count From Baseline Day 1 to Week 96
Time frame: Baseline at Day 1 and Week 96
Mean Change of Plasma CD4+ T-Cell Count From Baseline Day 1 to Week 144
Time frame: Baseline at Day 1 and Week 144
Percentage of Participants With Treatment-Emergent, Resistance-associated Substitutions at Week 48
Time frame: Up to Week 48
Mean Change From Baseline in Fasting Low Density Lipoprotein Cholesterol (LDL-C) at Week 48
Time frame: Baseline and Week 48
Mean Change From Baseline in Fasting Non-High Density Lipoprotein Cholesterol (Non-HDL-C) at Week 48
Time frame: Baseline and Week 48
Participants With One or More AEs at Week 96
Time frame: Up to Week 96
Participants With One or More AEs at Week 144
Time frame: Up to Week 144
Percentage of Participants With AEs Leading to Discontinuation of Study Intervention at Week 96
Time frame: Up to Week 96
Percentage of Participants With AEs Leading to Discontinuation of Study Intervention at Week 144
Time frame: Up to Week 144
Percentage of Participants With One or More AEs From Week 48 up to Week 96
Time frame: Week 48 up to Week 96
Percentage of Participants With One or More AEs From Week 48 up to Week 144
Time frame: Week 48 up to Week 144
Percentage of Participants With AEs Leading to Discontinuation of Study Intervention From Week 48 up to Week 96
Time frame: Week 48 up to Week 96
Percentage of Participants With AEs Leading to Discontinuation of Study Intervention From Week 48 up to Week 144
Time frame: Week 48 up to Week 144
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 21 Nov 2025.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 42213454Diamond 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.
- Derived from this study: PubMed 41654374Orkin 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.
- Merck Clinical Trials InformationLink provided by the sponsor.
- Individual participant dataSharing planned: Yes. https://trialstransparency.msdclinicaltrials.com/pdf/ProcedureAccessClinicalTrialData.pdf
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Medical Director study director
Merck Sharp & Dohme LLC
53 sites in 8 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing ART and DOR/ISL in people with HIV-1 Infection, run by Merck Sharp & Dohme LLC at 53 sites in 8 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: under way, not looking for participants, as of the sponsor's last update on 21 Nov 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 53 sites in United States, South Africa, United Kingdom, Switzerland, Australia and 3 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 21 Nov 2025). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Percentage of Participants With HIV-1 RNA ≥50 Copies/mL at Week 48 (time frame: Week 48). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT05631093, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 21 Nov 2025.