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

Mireille Mpoudi-Etame; Tamara Tovar Sanchez; Marwân-Al-Qays Bousmah; Pierrette Omgba Bassega; Justin Olinga; Eric Mimbe; Michel Foalem; Camille Chiep; Serge Edimo; Marie Varloteaux; Raphaël Pelloquin; Nadine Lamare; Sylvie Boyer; Martine Peeters; Jacques Reynes; Alexandra Calmy; Andrew Hill; Eric Delaporte; Charles Kouanfack; New Antiretroviral and Monitoring Strategies in HIV-infected Adults in Low-income countries (NAMSAL-ANRS-12313) study group

doi:10.1093/ofid/ofad582

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

Open Forum Infect Dis. 2023 Nov 20;10(12):ofad582. doi: 10.1093/ofid/ofad582. eCollection 2023 Dec.

Authors

Mireille Mpoudi-Etame^{1

2}, Tamara Tovar Sanchez³, Marwân-Al-Qays Bousmah^{4

5}, Pierrette Omgba Bassega⁶, Justin Olinga², Eric Mimbe², Michel Foalem^{2

7}, Camille Chiep², Serge Edimo², Marie Varloteaux², Raphaël Pelloquin³, Nadine Lamare⁸, Sylvie Boyer^{4

5}, Martine Peeters³, Jacques Reynes^{3

9}, Alexandra Calmy¹⁰, Andrew Hill¹¹, Eric Delaporte^{3

9}, Charles Kouanfack^{6

7

12}; New Antiretroviral and Monitoring Strategies in HIV-infected Adults in Low-income countries (NAMSAL-ANRS-12313) study group

Collaborators

New Antiretroviral and Monitoring Strategies in HIV-infected Adults in Low-income countries (NAMSAL-ANRS-12313) study group:
E Delaporte, A Ayouba, A Agholeng, C Butel, B Granouillac, A Lacroix, S Leroy, M Peeters, R Pelloquin, L Serrano, J Reynes, T Tovar-Sanchez, N Vidal, C Kounfack, M Foalem, P J Fouda, R Mougnoutou, J Olinga, V Omgba, S C Tchokonte Ngandé, B Ymele, M Mpoudi-Etamé, L Donfack, A Kambi, C D Epoupa Mpacko, M Fotso, R Moukoko, T Nké, P Omgba Bassega, A Akamba, S Lekelem, S Ngono, S B Tongo Fotack, M Tanga, M Tsafack, A Bissek, L Ciaffi, S Lem, E D Mimbé, M Niba, N Camille, J Olinga, M Varloteaux, E Mpoudi-Ngolé, E Ebong, N Lamare, G Edoul Mbesse, M Tongo, S Boyer, M Bousmah, P Huynh, G Maradan, M L Nishimwe, B Spire, G Peytavin, M P Lê, Y Yazdanpanah, A Diallo, I Fournier, A Montoyo, N Mercier, V Petrov-Sanchez, J Jean-Rassat, C Rekacewicz, C Perez Casas

Affiliations

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 Service de Maladies Infectieuses, Centre Hospitalier Universitaire de Montpellier, 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

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.

Keywords: HIV-1; dolutegravir; efficacy-durability; low-dose-efavirenz; weight gain.

Associated data

ClinicalTrials.gov/NCT02777229