Durability of the Efficacy and Safety of Dolutegravir-Based and Low-Dose Efavirenz–Based Regimens for the Initial Treatment of Human Immunodeficiency Virus Type 1 Infection in Cameroon: Week 192 Data of the NAMSAL-ANRS-12313 Study
Author:
Mpoudi-Etame Mireille12ORCID, Tovar Sanchez Tamara3ORCID, Bousmah Marwân-al-Qays45ORCID, Omgba Bassega Pierrette6, Olinga Justin2, Mimbe Eric2ORCID, Foalem Michel27ORCID, Chiep Camille2, Edimo Serge2, Varloteaux Marie2ORCID, Pelloquin Raphaël3, Lamare Nadine8, Boyer Sylvie45ORCID, Peeters Martine3ORCID, Reynes Jacques39ORCID, Calmy Alexandra10ORCID, Hill Andrew11ORCID, Delaporte Eric39ORCID, Kouanfack Charles6712ORCID, Delaporte E, Ayouba A, Agholeng A, Butel C, Granouillac B, Lacroix A, Leroy S, Peeters M, Pelloquin R, Serrano L, Reynes J, Tovar-Sanchez T, Vidal N, Kounfack C, Foalem M, Fouda P J, Mougnoutou R, Olinga J, Omgba V, Tchokonte Ngandé S C, Ymele B, Mpoudi-Etamé M, Donfack L, Kambi A, Epoupa Mpacko C D, Fotso M, Moukoko R, Nké T, Omgba Bassega P, Akamba A, Lekelem S, Ngono S, Tongo Fotack S B, Tanga M, Tsafack M, Bissek A, Ciaffi L, Lem S, Mimbé E D, Niba M, Camille N, Olinga J, Varloteaux M, Mpoudi-Ngolé E, Ebong E, Lamare N, Edoul Mbesse G, Tongo M, Boyer S, Bousmah M, Huynh P, Maradan G, Nishimwe M L, Spire B, Peytavin G, Lê M P, Yazdanpanah Y, Diallo A, Fournier I, Montoyo A, Mercier N, Petrov-Sanchez V, Jean-Rassat J, Rekacewicz C, Perez Casas C,
Affiliation:
1. Service Spécialisé d'Epidemiologie et Maladies Infectieuses, Hopital Militaire de Région No.1 Yaoundé , Yaoundé , Cameroon 2. Site Agence Nationale de Recherche sur le Sida et Maladies Infectieuses Emergentes du Cameroun, Yaoundé Central Hospital , Cameroon 3. TransVIHMI, Université de Montpellier, Institute de Recherche pour le Développement, Inserm , Montpellier , France 4. Aix Marseille Univ, Inserm, Institut de Recherche pour le Développement, Sciences Economiques et Sociales de la Santé et Traitement de l'Information Médicale, Institut Science de la Santé Publique d'Aix-Marseille , Marseille , France 5. Université Paris Cité, Institute de Recherche pour le Développement, Inserm, Ceped , F-75006 Paris , France 6. Unité de prise en charge du VIH, Hôpital de District de la Cité Verte , Yaoundé , Cameroon 7. Faculty of Medicine and Pharmaceutical Sciences, University of Dschang , Cameroon 8. Centre de Recherches sur les Maladies Emergentes et Ré-émergentes , Yaoundé , Cameroon 9. ervice de Maladies Infectieuses, Centre Hospitalier Universitaire de Montpellier S , Montpellier , France 10. Service des maladies infectieuses, Hôpital Universitaire de Genève , Geneva , Switzerland 11. Department of Pharmacology and Therapeutics, University of Liverpool , Liverpool , United Kingdom 12. Hôpital du Jour, Hôpital Central de Yaoundé , Cameroon
Abstract
Abstract
Background
A prospective study was extended to the new antiretroviral and monitoring strategies in HIV-infected adults in low-income countries (NAMSAL-ANRS)-12313 trial, a 96-week open-label, multicenter, randomized phase 3 trial comparing dolutegravir (DTG) 50 mg with efavirenz 400 mg (EFV400), both administered with tenofovir disoproxil fumarate and lamivudine (TDF/3TC) as first-line treatment for antiretroviral therapy (ART)–naive people living with human immunodeficiency virus type 1 (HIV). Noninferiority of DTG to EFV400 was demonstrated at 48-week and sustained at 96 weeks. Here, we present results at 192-week.
Methods
Previous trial participants were reconsented and followed up on their initial randomization arm (1:1 DTG/TDF/3TC:EFV400/TDF/3TC). Assessments included changes in viral suppression, biological parameters, and new serious adverse events (SAEs).
Results
Among the participants enrolled in the trial, 81% (499/613) were analyzed at week 192: 84% (261/310) on DTG/TDF/3TC and 78% (238/303) on EFV400/TDF/3TC. HIV RNA suppression was maintained in 69% (214/310) on DTG/TDF/3TC-based and 62% (187/303) on EFV400/TDF/3TC-based regimens (difference, 7.3% [95% confidence interval, −.20 to 14.83]; P = .057). Five (DTG/TDF/3TC = 2; EFV400/TDF/3TC = 3) new viral failures (World Health Organization definition) without related resistance DTG mutations and 24 new SAEs were observed (DTG/TDF/3TC = 13; EFV400/TDF/3TC = 11). Mean weight gain was +9.4 kg on DTG/TDF/3TC and +5.9 kg on EFV400/TDF/3TC. The percentage of participants with obesity increased from 6.9% to 27.7% on DTG/TDF/3TC (P < .0001) and from 8.3% to 16.7% on EFV400/TDF/3TC (P = .0033).
Conclusions
Four-year follow-up of people with HIV on DTG- and EFV400-based regimens showed long-term efficacy and safety of both ARTs, markedly among participants on DTG/TDF/3TC with high baseline viral load. However, unexpected substantial weight gain over time was prominent among participants on DTG/TDF/3TC, which should be closely monitored.
Clinical Trials Registration. NCT02777229.
Funder
French National Agency for AIDS and Emerging Infectious Diseases Research Unitaid
Publisher
Oxford University Press (OUP)
Subject
Infectious Diseases,Oncology
Reference26 articles.
1. Projected uptake of new antiretroviral (ARV) medicines in adults in low- and middle-income countries: a forecast analysis 2015–2025;Gupta;PLoS One,2016 2. Antiretroviral medicines in low- and middle-income countries: forecasts of global and regional demand for 2021–2025;World Health Organization (WHO),2022 3. Pocket book of primary health care for children and adolescents: guidelines for health promotion, disease prevention and management from the newborn period to adolescence;World Health Organization (WHO) Regional Office for Europe,2022 4. Dolutegravir plus abacavir–lamivudine for the treatment of HIV-1 infection;Walmsley;N Engl J Med,2013 5. Efficacy and safety of lower dose tenofovir disoproxil fumarate and efavirenz versus standard dose in HIV-infected, antiretroviral-naive adults: a multicentre, randomized, noninferiority trial;Chen;Emerg Microbes Infect,2020
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