According to results of a study published in the New England Journal of Medicine, treatment with dolutegravir and either of 2 tenofovir prodrugs, tenofovir alafenamide fumarate (TAF) or tenofovir disoproxil fumarate (TDF), is noninferior to standard HIV antiretroviral regimens.
Using a 96-week, phase 3, open-label, randomized trial, investigators compared a triple therapy combination of emtricitabine and dolutegravir plus TAF or TDF with the local South African standard regimen of TDF-emtricitabine-efavirenz (ClinicalTrials.gov identifier: NCT03122262). A total of 1053 patients who were aged ≥12 years, had not received antiretroviral therapy in the last 6 months, and had a creatine clearance of ≥60 mL/minute (<80 mL/minute for those aged <19 years) and an HIV type 1 RNA level of ≥500 viral copies/mL were included in the study cohort.
The study was conducted between February 2017 and May 2018; the median age of participants was 32 years. The mean CD4 count was 337 cells/mm3. Patients were randomly assigned (in a 1:1:1 ratio) to receive TAF-emtricitabine-dolutegravir as 2 tablets daily (TAF-based group), TDF-emtricitabine-dolutegravir as 2 tablets daily (TDF-based group), or TDF-emtricitabine-efavirenz as a single tablet daily (standard care group). At week 48, 84% of the TAF based group had met the primary endpoint of HIV1 RNA levels less than 50 copies. The percentages of the TDF and standard care groups, respectively, were 85% and 79%.
According to these findings, the dolutegravir-based therapies were deemed noninferior. Also, the number of patients who discontinued the trial regimen was higher in the standard care group compared with in both of the other groups. The TAF-based treatment had less effect than the others on bone density and renal function, but weight gains were greatest in this group and among females. No resistance to integrase inhibitors was found in either of the dolutegravir-containing regimens.
Investigators concluded that dolutegravir in combination with either of the tenofovir prodrugs is therefore noninferior to the standard care regimen of TDF-emtricitabine-efavirenz. However, there was significantly more weight gain in the dolutegravir groups, and those in the TAF group had a higher risk for obesity than patients from the other 2 groups.
Venter WDF, Moorhouse M, Sokhela S, et al. Dolutegravir plus two different prodrugs of tenofovir to treat HIV. New Engl J Med. 2019;381:803-815.