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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., Competing Interests: Potential conflicts of interest. A. C. was a member of the WHO guideline panel in 2018 and 2019. The HIV Unit of Geneva University Hospitals (HUG) received unrestricted educational grants from ViiV, AbbVie, Gilead, and MSD, all of which also provided financial support to the LIPO group and metabolism (day hospital) in the HIV/AIDS Unit of HUG. J. R. has received personal fees and grants from Gilead, MSD, Pfizer, Tibotec-Janssen, and ViiV Healthcare for participation in advisory boards, educational programs, and conferences. All other authors report no potential conflicts., (© The Author(s) 2023. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

Background: We provide new and comprehensive evidence on the evolution of a wide range of patient-reported outcomes (PROs) in the NAMSAL ANRS 12313 trial in Cameroon (2016-2021)-the first randomized comparison of dolutegravir 50 mg (DTG) and low-dose efavirenz (ie, 400 mg; EFV400) in treatment-naive adults living with HIV-1 in sub-Saharan Africa., Methods: We first described the evolution of PROs between baseline and week 192. Then, we used random-effects models to measure the effect of time since the initiation of antiretroviral therapy and the differential effect of DTG versus EFV400 on each PRO, adjusting for clinical, demographic, and socioeconomic factors, while accounting for unobserved heterogeneity and missing data., Results: Among the 613 patients randomized (DTG arm, n = 310; EFV400 arm, n = 303), (1) physical and mental health-related quality of life improved by 13.3% and 6.8%, respectively, (2) the percentage of patients with depression, anxiety, and stress decreased from 23.3%, 23.0%, and 7.7% to 3.1%, 3.5%, and 0.4%, respectively, and (3) the mean number of HIV-related symptoms decreased from 7.2 to 3.0 ( P < 0.001). For most PROs, no significant difference was found between both arms, even when accounting for the effect of DTG on weight gain. Nevertheless, our results suggest smaller improvements in mental health outcomes in the DTG arm, with a 5 percentage point higher adjusted probability of having anxiety at week 192 ( P < 0.01)., Conclusions: Although supporting the current World Health Organization guidelines recommending DTG-based and EFV400-based regimens as preferred and alternative first-line antiretroviral therapy, further studies should investigate medium-term mental health outcomes in patients on DTG., Trial Registration: ClinicalTrials.gov : NCT02777229., Competing Interests: The authors have no funding or conflicts of interest to disclose., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)