IMPOWER-022
IMPOWER-022: A Phase 3 Clinical Study on Oral Islatravir as Preexposure Prophylaxis in Cisgender Women
Overview
The IMPOWER-022 study is a groundbreaking Phase 3 clinical trial aimed at evaluating the efficacy and safety of oral Islatravir (ISL) administered once monthly (QM) as preexposure prophylaxis (PrEP) for cisgender women at high risk of HIV-1 infection. This randomized, active-controlled, double-blind study compares ISL QM with the standard of care, oral FTC/TDF taken daily (QD), to provide an alternative and potentially more convenient PrEP option for women
Study Rationale
Cisgender women in sub-Saharan Africa bear a disproportionate burden of the HIV epidemic, yet adherence challenges with daily PrEP regimens limit their effectiveness. A once-monthly oral PrEP option like Islatravir could address these challenges by improving adherence and offering a viable alternative. This study aims to generate critical data on the safety, tolerability, and efficacy of ISL QM compared to FTC/TDF QD, advancing the options available for HIV prevention.
Primary Objectives
- Efficacy: Evaluate the ability of ISL QM to prevent HIV-1 infections compared to FTC/TDF QD, as measured by the annual incidence rate of confirmed infections.
- Safety and Tolerability: Assess the safety profile of ISL QM compared to FTC/TDF QD through a comprehensive review of accumulated safety data.
Study Population
The study targets cisgender women aged 16–45 years who are at high risk for HIV-1 infection.
Investigators
Principal Investigator: Prof. Sinead Delany-Moretlwe
Abstract
Effect of Islatravir on Total Lymphocyte and Lymphocyte Subset Counts
Kathleen E.Squires, Todd A.Correll, Michael N.Robertson, Stephanie O.Klopfer, Peggy May Tan Hwang, Yun-Ping Zhou, Elizabeth Martin, Elizabeth G.Rhee. Conference on Retroviruses and Opportunistic Infections (CROI, Seattle, Washington, 19-22 February 2023
Background: Islatravir (ISL) is a nucleoside reverse transcriptase translocation inhibitor (NRTTI) being studied for HIV-1 treatment and prevention. Decreases in total lymphocyte counts and CD4+ T-cell counts were observed in several ISL clinical trials. We conducted comprehensive lymphocyte and lymphocyte subset analyses in Phase 2 and Phase 3 clinical trials evaluating oral ISL with doravirine (DOR) once daily (QD), oral ISL with MK-8507 once weekly (QW), or oral ISL alone once monthly (QM).
Methods: These analyses included 4 studies of ISL for HIV-1 treatment: one Phase 2 dose-ranging study of ISL 0.25, 0.75, and 2.25 mg QD with DOR 100 mg (±3TC) in treatment-naïve adults (P011), one Phase 2 dose-ranging study of ISL 20 mg with MK-8507 QW in virologically suppressed adults (P013), and two Phase 3 switch studies of DOR/ISL 100 mg/0.75 mg QD in virologically suppressed adults (P017 and P018); as well as 3 studies of ISL for pre-exposure prophylaxis (PrEP): one Phase 2 dose-ranging study of ISL 60 mg and 120 mg QM (P016) and two Phase 3 studies of ISL 60 mg QM (P022 and P024). For each study, the mean percent change from baseline in total lymphocyte counts and lymphocyte subset counts (CD4+ and CD8+ T-cells, B-cells, and NK-cells) were calculated by treatment group.
Results: In treatment-naïve participants (P011), increases in total lymphocyte counts (Table) and lymphocyte subset counts were similar for the ISL 0.25-mg group and the DOR/3TC/TDF group and were more favorable than changes observed in the ISL 0.75-mg or 2.25-mg groups. In participants switched to DOR/ISL 100 mg/0.75 mg QD (P017 and P018), decreases in total lymphocyte counts and lymphocyte subset counts reached a nadir on average between Weeks 48 and 72. In participants switched to ISL 20 mg + MK-8507 100, 200, or 400 mg QW (P013) and participants receiving ISL 60 or 120 mg QM for PrEP (P016, P022, and P024), decreases in total lymphocyte counts (Table) and lymphocyte subset counts were greater than those in participants receiving DOR/ISL 100 mg/0.75 mg QD (P017 and P018).
Conclusions: The magnitude of decreases in total lymphocyte counts and lymphocyte subset counts observed with ISL is exposure-dependent, with the 0.25-mg QD dose having lymphocyte changes comparable to standard of care antiretroviral therapy.
Latest Update
December 2024
For more information about IMPOWER-022 Study, please email to rhicomms@wrhi.ac.za
