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

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  1   2 , Tamara Tovar Sanchez  3 , Marwân-Al-Qays Bousmah  4   5 , Pierrette Omgba Bassega  6 , Justin Olinga  2 , Eric Mimbe  2 , Michel Foalem  2   7 , Camille Chiep  2 , Serge Edimo  2 , Marie Varloteaux  2 , Raphaël Pelloquin  3 , Nadine Lamare  8 , Sylvie Boyer  4   5 , Martine Peeters  3 , Jacques Reynes  3   9 , Alexandra Calmy  10 , Andrew Hill  11 , 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, Affiliations

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 et al. Open Forum Infect Dis. .

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.

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Conflict of interest statement

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.

Figures

Figure 1.
Figure 1.
Participant flowchart. Abbreviations: DTG, dolutegravir; EFV400, efavirenz 400 mg; HIV-1, human immunodeficiency virus type 1; PP, per protocol.
Figure 2.
Figure 2.
Evolution of the proportion of patients with human immunodeficiency virus type 1 (HIV-1) with a viral load (VL) <50 copies/mL over 192 weeks. A, Evolution of the proportions (with vertical bars for confidence intervals [CI]) of patients with a VL <50 copies/mL over time according to the treatment group (dolutegravir [DTG]/tenofovir disoproxil fumarate [TDF]/lamivudine [3TC] or efavirenz 400 mg [EFV400]/TDF/3TC). B, Evolution of the proportions (with vertical bars for CI) of patients with a VL <50 copies/mL over time according to the treatment group (DTG/TDF/3TC or EFV400/TDF/3TC) and the baseline VL (<100 000 vs ≥100 000 copies/mL).
Figure 3.
Figure 3.
Weight-related outcomes per treatment group over 192 weeks. The figure shows the evolution over follow-up of participants’ mean weight (A), participants’ mean body mass index (B), and the proportion of patients with obesity (C). Abbreviations: BMI, body mass index; CI, confidence interval; DTG, dolutegravir; EFV400, efavirenz 400 mg; W, week.
See this image and copyright information in PMC

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