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


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.