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
Authors: Mpoudi-Etame Mireille , Tovar Sanchez Tamara , Bousmah Marwân-al-Qays , Omgba Bassega Pierrette , Olinga Justin , Mimbe Eric , Foalem Michel , Chiep Camille , Edimo Serge , Varloteaux Marie , Pelloquin Raphaël , Lamare Nadine , Boyer Sylvie , Peeters Martine , Reynes Jacques , Calmy Alexandra , Hill Andrew , Delaporte Eric , Kouanfack Charles ,   New Antiretroviral and Monitoring Strategies in HIV-infected Adults in Low-income countries (NAMSAL-ANRS-12313) study group, 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 
Published: November 2023

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 &lt; .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.