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)

Q: What is IMPALA investigating and why is it important for sub-Saharan Africa?

IMPALA tests whether switching from daily oral ART to long-acting injectable cabotegravir and rilpivirine is non-inferior in effectiveness while maintaining safety. The focus is improving HIV-1 control for adults with a history of sub-optimal daily pill adherence.

Q: How are participants assigned to treatment in the randomized phase?

After consent and eligibility screening, viraemic participants are suppressed on oral ART before randomization. On Day 1, participants are randomized 1:1 to continue daily oral ART or switch to CAB LA + RPV LA Q2M, with or without a 1-month oral lead.

Q: What is the primary endpoint and when is it measured?

The primary endpoint is achieving HIV-1 RNA <50 copies/mL at 12 months based on the FDA snapshot approach.

Aug 23, 2026

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Long-acting injectable therapy for HIV-1 aims to reduce dosing frequency while improving privacy and adherence compared with daily oral antiretroviral combinations. The protocol evaluates cabotegravir (CAB) and rilpivirine (RPV) given as intramuscular injections every 2 months (CAB LA + RPV LA Q2M) versus continued first-line daily oral ART with 2 NRTIs plus dolutegravir in adults with prior sub-optimal adherence. IMPALA is an open-label multicentre randomized trial in Uganda, Kenya, and South Africa, with 540 participants followed for 24 months, assessing non-inferior viral suppression and safety.

LanguageEnglish

CategoryResearch & Report

FormatPDF

Pages18

Reading Time45 min

AccessFree to download

Study overview and rationale

Intervention and comparator

Eligibility screening and suppression procedure

Randomization and trial procedures

Treatment arms and oral lead

Follow-up schedule and endpoints

Trial registration and administrative information

STUDY PROTOCOL Efficacy and Safety of Long-acting Injectable Cabotegravirand Rilpivirine in Improving HIV-1 Control in sub-Saharan Africa: Protocol for a Phase 3b Open-Label Randomized Controlled Trial (IMPALA) [version 1; peer review: 1 approved] Victoria Babirye Tumusiime 1, Eugene Ruzagira 1,2, Claire Norcross 1,3, Ingrid Eshun-Wilsonova4, Jonathan Kitonsa 1,3, Ubaldo Mushabe Bahemuka 1, Daniel Grint 2, Geofrey Kimbugwe 1, Ayoub Kakande 1, David S Lawrence5-7, Fridah Mwendia 8, Rodica Van Solingen9, Veerle Van Eygen9, Fafa Addo Boateng 10, Fiona Cresswell 1,3,5, IMPALA study team 1 HIV interventions, MRC/UVRI and LSHTM Uganda Research Unit, Entebbe, Central Region, 256, Uganda 2 Department of Infectious Diseases Epidemiology, London School of Hygiene and Tropical Medicine Faculty of Epidemiology and Population Health, London, England, UK 3Global Health and Infectious, Brighton and Sussex Medical School, Brighton, England, UK 4Johnson & Johnson, CapeTown, South Africa 5 Department of Clinical Research, London School of Hygiene and Tropical Medicine Faculty of Infectious and Tropical Diseases, London, England, UK 6 Botswana Harvard Health Partnership, Gaborone, Botswana 7School of Pathology, Faculty of Health Sciences , University of Witwatersrand, Johannesburg, South Africa 8Johnson & Johnson, East Africa, Nairobi, Kenya 9Jansenn Research and Development, Beerse, Belgium 10Johnson & Johnson Middle East FZ LLC, Accra, Ghana v1 First published: 28 Mar 2025, 10:166 [https://doi.org/10.12688/wellcomeopenres.23363.1](https://doi.org/10.12688/wellcomeopenres.23363.1) [Latest published:](Latest published: 28 Mar 2025)[ 28 Mar 2025](Latest published: 28 Mar 2025), 10:166 [https://doi.org/10.12688/wellcomeopenres.23363.1](https://doi.org/10.12688/wellcomeopenres.23363.1) Abstract 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, Open Peer Review Approval Status 1 1. Eisuke Adachi, The University of Tokyo, IMSUT Hospital, Tokyo, Japan Any reports and responses or comments on the article can be found at the end of the article. 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](Clinical Trials.gov) on 19 September 2022 (NCT05546242), available from [https://clinicaltrials.gov/ct2/show/NCT05546242](https:/

FAQs

What is IMPALA investigating and why is it important for sub-Saharan Africa?

IMPALA tests whether switching from daily oral ART to long-acting injectable cabotegravir and rilpivirine is non-inferior in effectiveness while maintaining safety. The focus is improving HIV-1 control for adults with a history of sub-optimal daily pill adherence.

How are participants assigned to treatment in the randomized phase?

After consent and eligibility screening, viraemic participants are suppressed on oral ART before randomization. On Day 1, participants are randomized 1:1 to continue daily oral ART or switch to CAB LA + RPV LA Q2M, with or without a 1-month oral lead.

What is the primary endpoint and when is it measured?

The primary endpoint is achieving HIV-1 RNA <50 copies/mL at 12 months based on the FDA snapshot approach.

Aug 23, 2026

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