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Initial: TMC278LAHTX3005 Version Amendment 1, 30 September 2022 Superseded by: TMC278LAHTX3005 Version Amendment 2, 3 June 2024 This clinical trial was registered on Clinical Trials.gov on 19 September 2022 (NCT05546242), available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 clinicaltrials.gov. The study was also registered on Pan African Clinical Trials Registry on 23 January 2023 (PACT202301600757432TMC278LAHTX3005), available from pactr.samrc.ac.za.