In terms of HIV-1 viral suppression at week 48, a dolutegravir-based regimen was noninferior to a low-dose efavirenz regimen (a 400-mg dose, known as EFV400), according to data published in the New England Journal of Medicine.
Researchers conducted an open-label, multicenter, randomized, phase 3 noninferiority trial of 613 adults with HIV-1 in Cameroon (ClinicalTrials.gov identifier: NCT02777229). Participants had an HIV-1 RNA viral load ≥1000 copies/mm and no previous antiretroviral therapy. Researchers randomly assigned participants to receive either dolutegravir or the EFV400 reference treatment.
At week 48, in the dolutegravir group, 231 (74.5%) of 310 participants had a viral load <50 copies/mm, whereas the same was true for 209 (69%) of 303 patients in the EVF400 group, resulting in a difference of 5.5% (95% CI, −1.6% to 12.7%; Pnoninferiority <.001). Among the 207 and 200 participants in the dolutegravir and EFV400 groups, with a baseline viral load ≥100,000 copies/mm, a viral load <50 copies/mm was observed in 66.2% of the dolutegravir group and 61.5% of the EFV400 group, for a difference of 4.7% (95% CI, −4.6% to 14.0%). In the dolutegravir group, virologic failure, defined as a viral load >1000 copies/mm, was observed in 3 patients compared with 16 in the EFV400 group. Median weight gain was 5 kg in the dolutegravir group and 3 kg in the EFV400 group, and the incidence of obesity in the 2 groups was 12.3% vs 5.4%, respectively.
In this study, “[t]he prevalence of primary resistance to tenofovir, lamivudine, or both was too low to evaluate the effect, particularly on the risk of functional dolutegravir monotherapy.”
Adherence to treatment was also observed to be high on the basis of scores on a validated questionnaire, but investigators recognize limitations to this measure.
Investigators concluded that “this phase 3 trial showed the noninferiority of a dolutegravir-based regimen, which is associated with a low risk of acquiring drug-resistance mutations, to a low-dose efavirenz–based regimen with regard to viral suppression at week 48 in a typical population of adults with HIV-1 infection in Cameroon.”
Therefore, the current World Health Organization recommendations to initiate antiretroviral therapy with a dolutegravir-based regimen are supported. Because of the finding that viral suppression was impaired in persons with high baseline viral loads, investigators also encouraged support for worldwide efforts for early diagnosis and treatment of HIV-1.
Finally, the researchers noted concerns related to dolutegravir use in women of childbearing potential, along with the risk for obesity, which also needs further exploration.
NAMSAL ANRS 12313 Study Group, Kouanfack C, Mpoudi-Etame M, et al. Dolutegravir-based or low-dose efavirenz-based regimen for the treatment of HIV-1. N Engl J Med. 2019;381:816-826.