Efficacy and Safety of Long-acting Injectable Cabotegravir and Rilpivirine in Improving HIV-1 Control in sub-Saharan Africa: Protocol for a Phase 3b Open-Label Randomized Controlled Trial (IMPALA).

Long-acting (LA) injectable therapy as treatment for HIV-1 infection offers reduced dosing frequency, increased discretion and provides an alternative to two or three-drug daily oral combinations. A parenteral LA formulation of cabotegravir (CAB) and rilpivirine (RPV) given by intramuscular (IM) injection every 2 months (CAB LA + RPV LA Q2M) has shown safety and efficacy in phase 3/3b trials and could increase treatment satisfaction and improve adherence in sub-Saharan Africa. IMPALA (IMProving HIV-1 Control in Africa using Long-Acting Antiretrovirals) is a randomized, controlled, open-label, multicentre, interventional study in Uganda, Kenya, and South Africa of 540 virologically suppressed adults living with HIV-1 infection with a history of sub-optimal adherence to daily oral ART . IMPALA seeks to demonstrate the non-inferior antiviral effectiveness of switching to CAB LA + RPV LA Q2M, compared to the continuation of first-line daily oral ART containing 2 nucleoside/nucleotide reverse transcriptase inhibitors (NRTIs) plus dolutegravir (DTG). After providing informed consent, participants are screened for eligibility. Those who are viraemic (HIV RNA ≥200 copies/mL) at screening will be suppressed (<200 copies/mL for ≥3 months) on oral ART prior to randomization. On Day 1, individuals will be randomized 1:1 to either continue daily oral ART, or switch to CAB LA + RPV LA Q2M, (intervention arm) with or without a 1-month oral lead consisting of once daily oral CAB + RPV. The total follow-up period is 24 months. The primary endpoint is HIV-1 RNA <50 copies/ml at 12 months by FDA snapshot. Initial: TMC278LAHTX3005 Version Amendment 1, 30 September 2022 Superseded by: TMC278LAHTX3005 Version Amendment 2, 3 June 2024 This clinical trial was registered on Clinical Trials.gov on 19 September 2022 (NCT05546242), available from https://clinicaltrials.gov/ct2/show/NCT05546242. The study was also registered on Pan African Clinical Trials Registry on 23 January 2023 (PACT202301600757432TMC278LAHTX3005), available from https://pactr.samrc.ac.za/TrialDisplay.aspx?TrialID=24291.