HIV-IPhase 3Impower-022NCT04644029
Oral ISL QM as PrEP in Cisgender Women at High Risk for HIV-1 Infection (MK-8591-022)
A Phase 3 study testing Islatravir and FTC/TDF in people with HIV-I and Human Immunodeficiency Virus Type 1, run by Merck Sharp & Dohme LLC at 24 sites in 3 countries.
Trial summary
This study will evaluate whether oral islatravir (ISL) is effective in preventing Human Immunodeficiency Virus Type 1 (HIV-1) infection in women at high-risk for HIV-1 infection. Read more about this study
- Who is it for?
- Ages 16 to 45 years, women onlyHealthy volunteers can take part
- Conditions the study is for
- HIV-I, Human Immunodeficiency Virus Type 1, Prophylaxis
- What is being tested?
- Islatravir and FTC/TDF
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 730 participants
- Where
- 24 sitesin 3 countries
- Study dates
- 24 Feb 2021to 11 Jun 2024
- 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 16 to 45 years
- Women only
- Healthy volunteers accepted
- Child, Adult
Who may be able to join
- Confirmed HIV-uninfected based on negative HIV-1/HIV-2 test results before randomization.
- Sexually active (vaginal and/or anal sex) with a male sexual partner in the 30 days prior to screening.
- High risk for HIV-1 infection.
- Not pregnant or breastfeeding, and one of the following conditions applies: Not a woman of childbearing potential (WOCBP) or is a WOCBP and is using an acceptable contraceptive method during the intervention period and for at least 42 days after the last dose.
- A WOCBP must have a negative pregnancy test within 24 hours prior to the first dose of study intervention.
Who cannot join
- Hypersensitivity or other contraindication to any of the components of the study interventions as determined by the investigator.
- Findings of chronic hepatitis B virus (HBV) infection or past HBV.
- Current or chronic history of liver disease.
- History of malignancy within 5 years of screening except for adequately-treated basal cell or squamous cell skin cancer, or in situ cervical cancer.
- Past or current use of cabotegravir, lenacapavir, or any other long-acting HIV prevention product.
- Currently participating in or has participated in an interventional clinical study with an investigational compound or device, within 30 days prior to Day 1.
- Expecting to conceive or donate eggs at any time during the study.
Trial locations and contacts
24 sites in 3 countries.
24 sites in 3 countries
United States13 sites
Ponce De Leon Center Grady Health ( Site 0066)
Atlanta, Georgia, 30308
University of Alabama at Birmingham-UAB Sexual Health Research Clinic (SHRC) ( Site 0064)
Birmingham, Alabama, 35205
The University of North Carolina at Chapel Hill-Medicine ( Site 0056)
Chapel Hill, North Carolina, 27599
Prisma Health Richland Hospital-Clinical Research Unit ( Site 0069)
Columbia, South Carolina, 29203
Prism Health North Texas, Oak Cliff Health Center ( Site 0070)
Dallas, Texas, 75208
The University of Mississippi Medical Center ( Site 0065)
Jackson, Mississippi, 39216
KC CARE Health Center-Clinical Trials ( Site 0059)
Kansas City, Missouri, 64111
University of Miami Miller School of Medicine-Infectious Disease ( Site 0076)
Miami, Florida, 33136
West Virginia University-Department of Medicine ( Site 0061)
Morgantown, West Virginia, 26506
Rutgers New Jersey Medical School-Clinical Research Center ( Site 0071)
Newark, New Jersey, 07103
Orlando Immunology Center ( Site 0068)
Orlando, Florida, 32803
Bronx Prevention Center ICAP ( Site 0062)
The Bronx, New York, 10451
MedStar Health Research Institute (MedStar Physician Based R-MedStar Washington Hospital Center ( Si
Washington D.C., District of Columbia, 20010
South Africa10 sites
Madibeng Centre for Research ( Site 0019)
Brits, North West, 0250
SA Medical Research Council - Chatsworth Clinical Research Site ( Site 0030)
Chatsworth, KwaZulu-Natal, 4092
Maternal Adolescent and Child Health Research (MatCH) ( Site 0025)
Durban, KwaZulu-Natal, 4001
Perinatal HIV Research Unit (PHRU)-HIV Prevention CRS ( Site 0023)
Johannesburg, Gauteng, 1864
Wits Reproductive Health and HIV Institute (WRHI)-Wits RHI Ward 21 Clinical Research site ( Site 002
Johannesburg, Gauteng, 2000
Helen Joseph Hospital-Clinical HIV Research Unit ( Site 0020)
Johannesburg, Gauteng, 2092
Aurum Institute Klerksdorp CRS ( Site 0029)
Klerksdorp, North West, 2571
Qhakaza Mbokodo Research Clinic ( Site 0017)
Ladysmith, KwaZulu-Natal, 3370
Setshaba Research Centre ( Site 0016)
Pretoria, Gauteng, 0152
Aurum Institute - Rustenburg ( Site 0022)
Rustenburg, North West, 0299
About this study
Official title: A Phase 3, Randomized, Active-Controlled, Double-blind Clinical Study to Evaluate the Efficacy and Safety of Oral Islatravir Once-Monthly as Preexposure Prophylaxis in Cisgender Women at High Risk for HIV-1 Infection
This study will evaluate whether oral islatravir (ISL) is effective in preventing Human Immunodeficiency Virus Type 1 (HIV-1) infection in women at high-risk for HIV-1 infection. The study will compare oral ISL taken once a month with standard-of-care medication for prevention of HIV-1 infection, emtricitabine/tenofovir disoproxil (FTC/TDF), taken once per day. The primary hypothesis is that oral ISL is more effective than FTC/TDF at reducing the incidence rate per year of confirmed HIV-1 infections.
Read the detailed description
Based on laboratory findings of decreased lymphocyte and CD4+ T-cell counts across the islatravir program, dosing of blinded study intervention was halted on 13-Dec-2021 and screening and randomization of new participants was ended. Blinded assessments conducted prior to this date are designated as Study Part 1. During Study Part 2, participants from Part 1 have the option to receive daily open-label FTC/TDF while continuing in the study for safety monitoring. Study Part 3 was added to unblind each participant's Part 1 study intervention assignment, continue participants on FTC/TDF, and monitor safety.
- Conditions
- HIV-I, Human Immunodeficiency Virus Type 1, Prophylaxis
- Being tested
- Islatravir, Placebo to FTC/TDF, FTC/TDF, Placebo to ISL
- Keywords
- Preexposure prophylaxis (PrEP), Prevention
- Medical subject headings
- Acquired Immunodeficiency Syndrome
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
IslatravirDrug
Also called MK-8591
Oral 60 mg tablet administered once monthly during Part 1.
Placebo to FTC/TDFDrug
0 mg tablet administered once daily during Part 1.
FTC/TDFDrug
Also called TRUVADA™, Emtricitabine/Tenofovir disoproxil, Emtricitabine/Tenofovir disoproxil fumarate
Each tablet contains 200 mg emtricitabine and 245 mg of tenofovir disoproxil (equivalent to 300 mg tenofovir disoproxil fumarate or 201.22 mg tenofovir disproxil phosphate), administered orally once daily in Parts 1, 2, and 3.
Placebo to ISLDrug
0 mg tablet administered orally once monthly in Part 1.
| Study group | Role | What they receive |
|---|---|---|
| ISL QM | Experimental | ISL (islatravir) once monthly AND placebo to FTC/TDF (emtricitabine/tenofovir disoproxil) once daily. Following study-wide cessation of ISL administration, participants had the option to receive open-label FTC/TDF administered once daily. Receives: Drug: Islatravir; Drug: Placebo to FTC/TDF |
| FTC/TDF QD | Active comparator | FTC/TDF (TRUVADA™ or generic product emtricitabine/tenofovir disoproxil) administered once daily. Placebo to ISL (islatravir) administered once monthly. Following study-wide cessation of ISL administration, participants had the option to continue on open-label FTC/TDF. Placebo was no longer administered once open label treatment began. Receives: Drug: FTC/TDF; Drug: Placebo to ISL |
What is being measured
The primary outcome is the main question the study is designed to answer.
Incidence Rate Per Year of Confirmed HIV-1 Infection Among Participants During Blinded Treatment +42 Days Post-Blind
Incidence rate per year of confirmed HIV-1 infections is the number of participants with confirmed HIV-1 infections during the assessment period divided by the number of person-years in the arm. Data are based on participants with confirmed HIV-1 infection. The originally planned primary statistical analysis was removed via amendment when open-label treatment was initiated.
Measured: Up to approximately 325 days
Number of Participants Who Experienced an Adverse Event (AE) During Blinded Treatment + 42 Days Post-Blind
An AE is 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 number of participants who experienced an AE will be reported for each treatment arm.
Measured: Up to approximately 325 days
Number of Participants Who Discontinued Blinded Study Treatment Due to an AE
An AE is 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 number of participants who discontinued blinded study treatment due to an AE will be reported for each treatment arm.
Measured: Up to 283 days
Secondary outcomes (1)
Incidence Rate Per Year During Blinded Treatment of Confirmed HIV-1 Infection Among ISL-Treated Participants
Incidence rate per year of confirmed HIV-1 infections is the number of participants with confirmed HIV-1 infections during the assessment period divided by the number of person-years in the arm. Data are based on participants with confirmed HIV-1 infection. The originally planned secondary statistical analysis was removed via amendment when open-label treatment was initiated.
Measured: Up to approximately 237 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 Nov 2020
- Study start24 Feb 2021
- Primary completion18 Jul 2023
- Study completion11 Jun 2024
Why it stopped: Voluntarily terminated due to benefit/risk assessment
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.
- Other trials for HIV-IStudies 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
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 730 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
- NCT04644029
- Sponsor's protocol ID
- 8591-022
- Other IDs
- MK-8591-022, 2021-001289-39
- Acronym
- Impower-022
- Status last verified
- Dec 2025
- First submitted
- 23 Nov 2020
- Last updated
- 4 Feb 2026
- 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
Study at a glance
From the registry record, last updated by the sponsor on 4 Feb 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 3, Randomized, Active-Controlled, Double-blind Clinical Study to Evaluate the Efficacy and Safety of Oral Islatravir Once-Monthly as Preexposure Prophylaxis in Cisgender Women at High Risk for HIV-1 Infection
- ClinicalTrials.gov ID
- NCT04644029
- Acronym / sponsor ID
- Impower-022 / 8591-022
- Conditions
- HIV-I, Human Immunodeficiency Virus Type 1, Prophylaxis
- Keywords
- Preexposure prophylaxis (PrEP), Prevention
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Voluntarily terminated due to benefit/risk assessment
- Enrolment
- 730 participants (actual)
- Lead sponsor
- Merck Sharp & Dohme LLCIndustry (pharma, biotech, devices)
- Study start
- 24 Feb 2021 (actual)
- Primary completion
- 18 Jul 2023 (actual)
- Study completion
- 11 Jun 2024 (actual)
- First posted
- 25 Nov 2020 (actual)
- Results
- Posted 9 Aug 2024
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This study will evaluate whether oral islatravir (ISL) is effective in preventing Human Immunodeficiency Virus Type 1 (HIV-1) infection in women at high-risk for HIV-1 infection. The study will compare oral ISL taken once a month with standard-of-care medication for prevention of HIV-1 infection, emtricitabine/tenofovir disoproxil (FTC/TDF), taken once per day. The primary hypothesis is that oral ISL is more effective than FTC/TDF at reducing the incidence rate per year of confirmed HIV-1 infections.
Detailed description
Based on laboratory findings of decreased lymphocyte and CD4+ T-cell counts across the islatravir program, dosing of blinded study intervention was halted on 13-Dec-2021 and screening and randomization of new participants was ended. Blinded assessments conducted prior to this date are designated as Study Part 1. During Study Part 2, participants from Part 1 have the option to receive daily open-label FTC/TDF while continuing in the study for safety monitoring. Study Part 3 was added to unblind each participant's Part 1 study intervention assignment, continue participants on FTC/TDF, and monitor safety.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| ISL QM | Experimental | Drug: Islatravir, Drug: Placebo to FTC/TDFISL (islatravir) once monthly AND placebo to FTC/TDF (emtricitabine/tenofovir disoproxil) once daily. Following study-wide cessation of ISL administration, participants had the option to receive open-label FTC/TDF administered once daily. |
| FTC/TDF QD | Active comparator | Drug: FTC/TDF, Drug: Placebo to ISLFTC/TDF (TRUVADA™ or generic product emtricitabine/tenofovir disoproxil) administered once daily. Placebo to ISL (islatravir) administered once monthly. Following study-wide cessation of ISL administration, participants had the option to continue on open-label FTC/TDF. Placebo was no longer administered once open label treatment began. |
Who may qualify
- Ages
- 16 to 45 years
- Sex
- Female only
- Healthy volunteers
- Accepted
- Age groups
- Child, Adult
Key inclusion criteria (5 listed)
- Confirmed HIV-uninfected based on negative HIV-1/HIV-2 test results before randomization.
- Sexually active (vaginal and/or anal sex) with a male sexual partner in the 30 days prior to screening.
- High risk for HIV-1 infection.
- Not pregnant or breastfeeding, and one of the following conditions applies: Not a woman of childbearing potential (WOCBP) or is a WOCBP and is using an acceptable contraceptive method during the intervention period and for at least 42 days after the last dose.
- A WOCBP must have a negative pregnancy test within 24 hours prior to the first dose of study intervention.
Key exclusion criteria (7 listed)
- Hypersensitivity or other contraindication to any of the components of the study interventions as determined by the investigator.
- Findings of chronic hepatitis B virus (HBV) infection or past HBV.
- Current or chronic history of liver disease.
- History of malignancy within 5 years of screening except for adequately-treated basal cell or squamous cell skin cancer, or in situ cervical cancer.
- Past or current use of cabotegravir, lenacapavir, or any other long-acting HIV prevention product.
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 |
|---|---|---|
| IslatravirAlso: MK-8591Oral 60 mg tablet administered once monthly during Part 1. | Drug | ISL QM |
| Placebo to FTC/TDF0 mg tablet administered once daily during Part 1. | Drug | ISL QM |
| FTC/TDFAlso: TRUVADA™, Emtricitabine/Tenofovir disoproxil, Emtricitabine/Tenofovir disoproxil fumarateEach tablet contains 200 mg emtricitabine and 245 mg of tenofovir disoproxil (equivalent to 300 mg tenofovir disoproxil fumarate or 201.22 mg tenofovir disproxil phosphate), administered orally once daily in Parts 1, 2, and 3. | Drug | FTC/TDF QD |
| Placebo to ISL0 mg tablet administered orally once monthly in Part 1. | Drug | FTC/TDF QD |
Primary outcome
Incidence Rate Per Year of Confirmed HIV-1 Infection Among Participants During Blinded Treatment +42 Days Post-Blind
Time frame: Up to approximately 325 days
Incidence rate per year of confirmed HIV-1 infections is the number of participants with confirmed HIV-1 infections during the assessment period divided by the number of person-years in the arm. Data are based on participants with confirmed HIV-1 infection. The originally planned primary statistical analysis was removed via amendment when open-label treatment was initiated.
Number of Participants Who Experienced an Adverse Event (AE) During Blinded Treatment + 42 Days Post-Blind
Time frame: Up to approximately 325 days
An AE is 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 number of participants who experienced an AE will be reported for each treatment arm.
Number of Participants Who Discontinued Blinded Study Treatment Due to an AE
Time frame: Up to 283 days
An AE is 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 number of participants who discontinued blinded study treatment due to an AE will be reported for each treatment arm.
1 secondary outcome
Incidence Rate Per Year During Blinded Treatment of Confirmed HIV-1 Infection Among ISL-Treated Participants
Time frame: Up to approximately 237 days
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 4 Feb 2026.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Merck Clinical Trials InformationLink provided by the sponsor.
- Plain Language SummaryLink 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
24 sites in 3 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Islatravir and FTC/TDF in people with HIV-I and Human Immunodeficiency Virus Type 1, run by Merck Sharp & Dohme LLC at 24 sites in 3 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 5 inclusion and 7 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: stopped early, as of the sponsor's last update on 4 Feb 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 24 sites in United States, South Africa, Uganda. 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 9 Aug 2024). 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?
Incidence Rate Per Year of Confirmed HIV-1 Infection Among Participants During Blinded Treatment +42 Days Post-Blind (time frame: Up to approximately 325 days). 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?
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 4 Feb 2026.