Year: 2026
Type: article
Study designs: Randomized Controlled Trial, Clinical Trial
Abstract: BACKGROUND: In eastern and southern Africa, approximately 1 million people living with human immunodeficiency virus (HIV) and receiving oral therapy do not have viral suppression because of adherence challenges. METHODS: We conducted a phase 3b, open-label, randomized trial to compare long-acting injectable cabotegravir plus rilpivirine with oral dolutegravir-based therapy among adults with virally suppressed HIV type 1 (viral load, <200 copies per milliliter) and suboptimal adherence or care engagement. The participants were assigned in a 1:1 ratio to receive intramuscular injections of cabotegravir (600 mg) plus rilpivirine (900 mg) every 8 weeks, with the first two injection visits occurring 4 weeks apart, or to continue daily oral dolutegravir-based therapy; baseline drug-resistance testing was not performed. The primary end point was a viral load of less than 50 copies per milliliter at week 48; noninferiority was assessed with a margin of -10 percentage points. Confirmed virologic failure (two consecutive viral loads of ≥200 copies per milliliter) was a key secondary end point. RESULTS: A total of 540 participants were enrolled across seven sites in Kenya, South Africa, and Uganda; 537 were included in the primary analysis. At 48 weeks, 244 of 268 participants (91.0%) in the long-acting-therapy group had a viral load of less than 50 copies per milliliter, as compared with 240 of 269 participants (89.2%) in the oral-therapy group (risk difference, 1.9 percentage points; 95% confidence interval [CI], -3.1 to 6.9), which met the criterion for noninferiority. The results of a per-protocol analysis were consistent with those of the primary analysis. Confirmed virologic failure occurred in 5 participants (1.9%) in the long-acting-therapy group and in no participants in the oral-therapy group (risk difference, 1.9 percentage points; 95% CI, 0.3 to 3.5). Serious adverse events were reported in 11 of 271 participants (4.1%) who received long-acting therapy and in 8 of 269 participants (3.0%) who received oral therapy (risk difference, 1.1 percentage points; 95% CI, -1.1 to 4.2). CONCLUSIONS: Among persons with HIV in Africa who have adherence challenges, long-acting cabotegravir plus rilpivirine was noninferior to oral dolutegravir-based therapy for maintaining a viral load of less than 50 copies per milliliter. (Funded by Johnson & Johnson; IMPALA ClinicalTrials.gov number, NCT05546242; Pan African Clinical Trials Registry number, PACT202301600757432TMC278LAHTX3005.).
Source: New England Journal of Medicine
Authors: Fiona V. Cresswell, Jonathan Kitonsa, Claire Norcross, Victoria Tumusiime, Loice Achieng Ombajo, Nigel Garrett, Sheetal Kassim, Noela C. Owarwo, Eva A. Laker Odongpiny, Ibrahim Yawe, Sharana Mahomed, Henry Mugerwa, Paddy L. Kafeero, Joseph Nkuranga, Ubaldo Bahemuka, Jane Nabbuto, Violet Ankunda, Phiona Nabaggala, Charles Ogwang, Geofrey Kimbugwe, Ayoub Kakande, Upasna Singh, Dorothie van der Vendt, Arnold Onyango, Eve Koile, David S. Lawrence, Awhonukeh Idahosa, Veerle van Eygen, Fafa Addo Boateng, Ingrid Eshun-Wilsonova, Daniel J. Grint, Eugene Ruzagira
Institutions: Brighton and Sussex Medical School, London School of Hygiene & Tropical Medicine, Uganda Virus Research Institute, University of Nairobi, University of Cape Town, Centre for the AIDS Programme of Research in South Africa, University College London, University of KwaZulu-Natal, Infectious Diseases Institute, University of St Andrews, Joint Clinical Research Centre, University of the Witwatersrand, Botswana Harvard AIDS Institute Partnership, Johnson & Johnson (United States)
Language: English
Subfield: Infectious Diseases
Field: Medicine
Domain: Health Sciences
Open Access status: green
OpenAlex ID: W7221816005