As the HIV epidemic continues to challenge healthcare systems, particularly in Sub Saharan Africa where the majority of global cases are concentrated, there is an urgent need for more effective and sustainable treatment options. Traditional antiretroviral therapy requires daily pill regimens, presenting challenges for long-term adherence and increasing the risk of treatment failure. In response, researchers are exploring innovative approaches to improve outcomes. The IMPALA trial, a Phase 3b study, is evaluating the efficacy, safety, and effectiveness of long-acting injectable cabotegravir and rilpivirine. This pragmatic trial, conducted at sevensites across Sub-Saharan Africa, is now fully recruited and will provide important, region-specific evidence in 2025.
Optimizing data collection
At a recent Investigators’ meeting in Nairobi, Kenya, researchers gathered to discuss the progress of the trial, updates from each participating site and plans for sub-studies. So far, several key milestones including the interim analysis have been reached, moving the study closer to its ultimate goal of improving HIV treatment outcomes.
The trial is fully recruited at all participating institutions, including the MRC/UVRI and LSHTM Uganda Research Unit, the Joint Clinical Research Centre (JCRC), Infectious Diseases Institute in Uganda, the Desmond Tutu HIV Foundation (DTHF), the Centre for the AIDS Programme of Research in South Africa (CAPRISA), Kenya’s Kenyatta National Hospital (KNH) and Jaramogi Oginga Odinga Teaching and Referral Hospital (JOOTRH). All partners have made significant steps in recruiting participants and maintaining retention, ensuring that the data collected is robust.
Ensuring the safety of trial participants is a top priority. The trial has maintained a rigorous safety monitoring system to track any adverse events, ensuring that the safety profile of the long-acting injectables is well documented. This effort is vital in the larger context of moving these treatments into more widespread use.
A convenient alternative to daily pills
The IMPALA trial builds on findings from the recently published CARES study in The Lancet, which evaluated theeffectiveness and safety of two injectable antiretrovirals, cabotegravir and rilpivirine, for HIV treatment. The CARES study demonstrated that receiving these injections every two months was just as effective as daily oral HIV medications for those starting treatment.
IMPALA takes this research a step further by focusing on individuals who have struggled to maintain control oftheir HIVdespite being on treatment. This population faces higher risks of disease progression and transmission. Researchers believe long-acting injectable treatment could be especially beneficial for these individuals.
Traditional oral HIV treatment regimens require daily medications, which can result in treatment fatigue, inconsistent adherence and virological failure. Long-acting injectables present a promising alternative by reducing the frequency of dosing from 365 days to six times a year, offering a more convenient and discreet approach.The combination of cabotegravir and rilpivirine not only simplifies the treatment regimen but also holds the potential to improve adherence, as patients are no longer burdened with daily pill taking.
Beyond the clinical benefits, long-acting injectables could significantly improve the lived experience of HIV treatment. Many people living with HIV face stigma, discrimination, and the ongoing psychological burden of managing a chronic condition.
The future of HIV care
Researchers are optimistic that long-acting injectables will become a key part of HIV prevention and treatment in sub-Saharan Africa and beyond. The IMPALA trial is also examining the cost-effectiveness of long-acting injectables compared to traditional oral ART, providing critical data for policymakers and healthcare providers. This evidence will help guide decisions on integrating long-acting injectables into national HIV treatment programs.
Read the latest publications from the study.
The IMPALA trial is located in the Unit’s vaccines research theme. Through key epidemiology and clinical trials, our team of vaccine researchers is working at all stages of the vaccine development pipeline to contribute to the development and implementation of relevant vaccines and context-specific techniques and measures for harnessing vaccine response and efficacy.
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