Oral ISL QM as PrEP in Cisgender Women at High Risk for HIV-1 Infection (MK-8591-022) (Impower-022)

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.

Study Overview

• Status: Terminated
• Conditions: Prophylaxis; Human Immunodeficiency Virus Type 1; HIV-I
• Intervention / Treatment: Drug: Islatravir; Drug: Placebo to FTC/TDF; Drug: FTC/TDF; Drug: Placebo to ISL

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 Type: Interventional
• Enrollment (Actual): 730
• Phase: Phase 3

Contacts and Locations

Study Locations

• South Africa
  • Gauteng
    • Johannesburg, Gauteng, South Africa, 1864
      • Perinatal HIV Research Unit (PHRU)-HIV Prevention CRS ( Site 0023)
    • Johannesburg, Gauteng, South Africa, 2000
      • Wits Reproductive Health and HIV Institute (WRHI)-Wits RHI Ward 21 Clinical Research site ( Site 002
    • Johannesburg, Gauteng, South Africa, 2092
      • Helen Joseph Hospital-Clinical HIV Research Unit ( Site 0020)
    • Pretoria, Gauteng, South Africa, 0152
      • Setshaba Research Centre ( Site 0016)
  • KwaZulu-Natal
    • Chatsworth, KwaZulu-Natal, South Africa, 4092
      • SA Medical Research Council - Chatsworth Clinical Research Site ( Site 0030)
    • Durban, KwaZulu-Natal, South Africa, 4001
      • Maternal Adolescent and Child Health Research (MatCH) ( Site 0025)
    • Ladysmith, KwaZulu-Natal, South Africa, 3370
      • Qhakaza Mbokodo Research Clinic ( Site 0017)
  • North West
    • Brits, North West, South Africa, 0250
      • Madibeng Centre for Research ( Site 0019)
    • Klerksdorp, North West, South Africa, 2571
      • Aurum Institute Klerksdorp CRS ( Site 0029)
    • Rustenburg, North West, South Africa, 0299
      • Aurum Institute - Rustenburg ( Site 0022)
• Uganda
  • Kampala, Uganda, 10216
    • MU-JHU Care Limited-Clinic ( Site 0041)
• United States
  • Alabama
    • Birmingham, Alabama, United States, 35205
      • University of Alabama at Birmingham-UAB Sexual Health Research Clinic (SHRC) ( Site 0064)
  • District of Columbia
    • Washington D.C., District of Columbia, United States, 20010
      • MedStar Health Research Institute (MedStar Physician Based R-MedStar Washington Hospital Center ( Si
  • Florida
    • Miami, Florida, United States, 33136
      • University of Miami Miller School of Medicine-Infectious Disease ( Site 0076)
    • Orlando, Florida, United States, 32803
      • Orlando Immunology Center ( Site 0068)
  • Georgia
    • Atlanta, Georgia, United States, 30308
      • Ponce De Leon Center Grady Health ( Site 0066)
  • Mississippi
    • Jackson, Mississippi, United States, 39216
      • The University of Mississippi Medical Center ( Site 0065)
  • Missouri
    • Kansas City, Missouri, United States, 64111
      • KC CARE Health Center-Clinical Trials ( Site 0059)
  • New Jersey
    • Newark, New Jersey, United States, 07103
      • Rutgers New Jersey Medical School-Clinical Research Center ( Site 0071)
  • New York
    • The Bronx, New York, United States, 10451
      • Bronx Prevention Center ICAP ( Site 0062)
  • North Carolina
    • Chapel Hill, North Carolina, United States, 27599
      • The University of North Carolina at Chapel Hill-Medicine ( Site 0056)
  • South Carolina
    • Columbia, South Carolina, United States, 29203
      • Prisma Health Richland Hospital-Clinical Research Unit ( Site 0069)
  • Texas
    • Dallas, Texas, United States, 75208
      • Prism Health North Texas, Oak Cliff Health Center ( Site 0070)
  • West Virginia
    • Morgantown, West Virginia, United States, 26506
      • West Virginia University-Department of Medicine ( Site 0061)

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 12 years to 41 years (Child, Adult)
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• 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.

Exclusion Criteria:

• 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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: ISL QM; 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.	Drug: Islatravir; Oral 60 mg tablet administered once monthly during Part 1.; Other Names: MK-8591; Drug: Placebo to FTC/TDF; 0 mg tablet administered once daily during Part 1.
Active Comparator: FTC/TDF QD; 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.	Drug: FTC/TDF; 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.; Other Names: TRUVADA™; Emtricitabine/Tenofovir disoproxil; Emtricitabine/Tenofovir disoproxil fumarate; Drug: Placebo to ISL; 0 mg tablet administered orally once monthly in Part 1.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	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.	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.	Up to 283 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	Up to approximately 237 days

Collaborators and Investigators

• Sponsor: Merck Sharp & Dohme LLC
• Investigators: Study Director: Medical Director, Merck Sharp & Dohme LLC

Publications and helpful links

Helpful Links

• Merck Clinical Trials Information
• Plain Language Summary

Study record dates

Study Major Dates

• Study Start (Actual): February 24, 2021
• Primary Completion (Actual): July 18, 2023
• Study Completion (Actual): June 11, 2024

Study Registration Dates

• First Submitted: November 23, 2020
• First Submitted That Met QC Criteria: November 23, 2020
• First Posted (Actual): November 25, 2020

Study Record Updates

• Last Update Posted (Actual): February 4, 2026
• Last Update Submitted That Met QC Criteria: January 15, 2026
• Last Verified: December 1, 2025

More Information

Terms related to this study

• Keywords: Prevention; Preexposure prophylaxis (PrEP)
• Additional Relevant MeSH Terms: Blood-Borne Infections; Urogenital Diseases; Genital Diseases; Immune System Diseases; Infections; RNA Virus Infections; Virus Diseases; Communicable Diseases; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; Immunologic Deficiency Syndromes; Slow Virus Diseases; HIV Infections; Acquired Immunodeficiency Syndrome; Organic Chemicals; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Pharmaceutical Preparations; Nucleic Acids, Nucleotides, and Nucleosides; Purines; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Organophosphorus Compounds; Nucleosides; Deoxyribonucleosides; Organophosphonates; Adenine; Drug Combinations; Tenofovir; Emtricitabine; Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination; islatravir
• Other Study ID Numbers: 8591-022; MK-8591-022 (Other Identifier: Merck); 2021-001289-39 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: https://trialstransparency.msdclinicaltrials.com/pdf/ProcedureAccessClinicalTrialData.pdf

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No