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Dolutegravir versus efavirenz-400 as first-line ART in Cameroon: week 192 data of NAMSAL trial

Title
Dolutegravir versus efavirenz-400 as first-line ART in Cameroon: week 192 data of NAMSAL trial
Presenter
Mireille Mpoudi-Etame
Authors
M. Mpoudi-Etame * (1), T. Tovar Sanchez (2), P. Omgba Bassega (3), J. Olinga (4), R. Pelloquin (2), M. Foalem (4), C. Njonkep (4), E. Mimbé (4), M. Varloteaux (4), M. Tongo (5), N. Lamare (5), M. Peeters (2), J. Reynes (6,2), E. Delaporte (6,2), S. Koulla-Shiro (4), C. Kouanfack (7,8,4), NAMSAL ANRS 12313 study group
Institutions
(1) Military Hospital of Yaoundé, Yaoundé, Cameroon, (2) TransVIHMI, University of Montpellier-IRD-INSERM, Montpellier, France, (3) District of the Cité Verte Hospital, Yaoundé, Cameroon, (4) Cameroon ANRS-site, Yaoundé, Cameroon, (5) CREMER, Yaoundé, Cameroon, (6) Montpellier University Hospital Center, Montpellier, France, (7) Faculty of Medicine and Pharmaceutical Sciences University of Dschang, Dschang, Cameroon, (8) Yaoundé Central Hospital, Yaoundé, Cameroon

BACKGROUND: The NAMSAL main objective was the comparison of two first-line antiretroviral treatments (ARTs) in real-life conditions in low- and middle-income countries (LMIC): dolutegravir 50 mg (DTG) and low-dose of efavirenz (ie 400 mg; EFV400) daily both combined with tenofovir-disoproxil-fumarate [TDF]/lamivudine [3TC]. The 48-week outcomes provided decision-making elements to World Health Organization (WHO) to recommend DTG as first-line ART in 2019. Outcomes were confirmed at 96 weeks. We assessed long-term efficacy and safety of these two regimens.
METHODS: NAMSAL was an open-label, multicenter, randomized, phase 3 non inferiority trial conducted in Cameroon over 96-week, extended as post-trial follow-up as a prospective cohort until 192-week. HIV-1 infected ARV-naive adults with HIV-RNA viral load (VL)>1000 copies/mL were randomized and maintained in the base arm (1-DTG:1-EFV). The primary end point was the proportion of participants with a VL of less than 50 copies/mL at week 48; secondary outcomes were assessed with superiority-test.
RESULTS: At week 192, proportions of participants with a VL of less than 50 copies/mL in intention-to-treat (ITT) were 69% (DTG: 214/310) and 62% (EFV400: 187/303) respectively (difference, 7.3%; CI-95%, [-0.20;14.83], p-value=0.057; Figure1). Per-protocol results were 75% (DTG: 172/230) and 66% (EFV400: 178/271) respectively (difference, 9.1%; CI-95%, [1.13;17.07], p-value=0.027). During the four-year of follow-up, five (DTG: 2; EFV400: 3) new virological failures (WHO-definition) without related resistance mutations and 24 new severe adverse-events (SAE) were observed (DTG: 13, EFV400: 11). Over four years, weight gain was more important on DTG group compared to EFV400 group: Median weight-gain (Women (W): DTG +8.0 Kg, EFV400 +5.0 Kg, p-value=0.010; Men (M): DTG +6.0 Kg, EFV400 +4.0 kg; p-value=0.024); Obesity incidence (W: DTG 17%, EFV400 11%, p-value=0.140; M: DTG 26%, EFV400 4%; p<0.001); Proportion of patients who had a weight-gain of at least 15% compared to their initial weight (W: DTG 43%, EFV400 31%, p-value=0.030; M: DTG 23%, EFV400 25%; p- value= 0.848; Figure2).
CONCLUSIONS: DTG-based and low dose EFV-based regimens has durable efficacy and safety for use in treatment-naïve patients with HIV-1. There was significantly more weight gain with the DTG-containing regimen.