The NAMSAL ANRS 12313 trial: HIV viral suppression similar for dolutegravir and low-dose efavirenz treatment

1. For previously untreated HIV-1 patients in Cameroon, treatment with dolutegravir was noninferior to low dose efavirenz at lowering viral load over a period of 48 weeks.

2. Weight gain occurred in both groups but was more evident in the dolutegravir treated patients.

Evidence Rating Level: 1 (Excellent)  

Study Rundown: For many years the World Health Organization recommended initial human immunodeficiency virus type 1 (HIV-1) antiretroviral therapy to consist of the non-nucleoside reverse-transcriptase inhibitor efavirenz 600mg, as part of a combination of three anti-retroviral drugs. Recent studies have suggested the integrase inhibitor dolutegravir may be an ideal first-line HIV therapy due to its efficacy, high barrier to resistance, low production costs, and the newly considered neurodevelopmental risks of efavirenz. To evaluate efficacy and safety of possible HIV therapies in a resource limited context, the phase 3 New Antiretroviral and Monitoring Strategies in HIV-Infected Adults in Low-Income Countries (NAMSAL) ANRS 12313 study compared low-dose efavirenz 400mg (EFV400), which had previously been shown to be noninferior to efavirenz 600mg,  to dolutegravir. The primary endpoint, the proportion of patients with a viral load of less than 50 copies/mL at 48 weeks, showed that dolutegravir was noninferior to EFV400. Virologic failure, having more than 1000 copies/mL, occurred in more EFV400 patients. Weight gain was notable in dolutegravir treated patients.

This study evaluates contested HIV treatment options in a resource limited country of Cameroon, providing more generalizable results than other similar studies conducted in different settings. A strength of the study is the extensive subgroup analysis while it is limited by its length of follow-up only out to 48 weeks and patients were only enrolled at hospitals in an urban setting.

Click to read the study in NEJM

Relevant Reading: Dolutegravir for the treatment of HIV

In-Depth [randomized controlled trial]: This phase 3, open-label, randomized controlled trial enrolled Cameroonian patients between 2016 and 2017. Eligible patients were adults with HIV-1 group m infection who had not yet received antiretroviral therapy. Use of contraceptive methods was required for women of childbearing age. Patients with severe liver, renal, psychiatric, or tuberculosis disease were excluded.  Patients were stratified during randomization by viral load and trial site, and assigned to a dolutegravir (n=292) or EFV400 (n=297) group. Analysis was performed on a per-protocol basis. The primary outcome, viral load of less than 50 copies/mL at week 48, occurred in 74.5% and 69.0% of dolutegravir and EFV400 patients, respectfully (difference of 5.5%, (95% confidence interval [CI], −1.6% to 12.7%), indicating noninferiority of dolutegravir but not superiority. For patients with a baseline viral load of greater than 100,000 copies/mL, 66.2% and 61.5% of dolutegravir and EFV400 patients had a viral load of less than 50 copies/mL at week 48 (4.7% difference; 95% CI, −4.6 to 14.0) showing dolutegravir noninferiority. When viral suppression was defined as less than 200 copies/mL at week 48 dolutegravir was both noninferior and superior compared to EFV400. In multiple subgroup analyses for efficacy dolutegravir trended towards showing superiority in viral load suppression. Of the women on trial drugs who became pregnant during the study, 13 and 12 on dolutegravir and EFV400, respectively, none had children born with congenital abnormalities. Median weight gain was greater in dolutegravir (5.0kg) compared to EFV400 (3.0kg) treated patients (P<0.001).

Image: PD

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