A fixed-dose combination of dolutegravir plus abacavir/lamivudine (Triumeq, DTG/ABC/3TC) proved virologically superior to once-daily ritonavir (Norvir)-boosted atazanavir (Reyataz) plus tenofovir/emtricitabine (Truvada) -- denoted as ATV/r + TDF/FTC -- in ARIA, an open-label international trial in women with HIV. Virologic response rates were consistent across racial/ethnic groups.
Dolutegravir (Tivicay, DTG), an unboosted integrase inhibitor, is coformulated with abacavir/lamivudine (ABC/3TC) as Triumeq and licensed for treatment of HIV infection in adults. An international team conducted ARIA between August 2013 and September 2015 to compare the efficacy and safety of DTG/ABC/3TC and ATV/r + TDF/FTC in women, and they presented results at IDWeek/IDSA 2016.
ARIA enrolled antiretroviral-naive women with a viral load above 500 copies/mL and randomized them 1:1 to one of the two study regimens for 48 weeks. Participants included 134 women from the United States, 66 from South Africa, 54 from Spain, 50 from Russia and 195 from Latin America, Europe and Thailand. In the DTG and ATV/r arms, median age stood at 37.5 and 37 years and respective proportions were blacks 41% and 44%, whites 46% and 43%, U.S. participants 25% and 28% and women with a pretreatment viral load above 100,000 copies/mL 28% and 27%.
Snapshot analysis determined that 82% of women randomized to DTG/ABC/3TC versus 71% randomized to ATV/r + TDF/FTC had a viral load below 50 copies/mL at week 48. The difference between groups (10.5%, 95% confidence interval 3.1% to 17.8%, P = .005) established the virologic superiority of DTG/ABC/3TC. Virologic nonresponse rates were 6% in the DTG/ABC/3TC arm and 14% in the ATV/r + TDF/FTC arm. Respective discontinuations for adverse events were 4% and 7%.
Among people with a pretreatment viral load above 100,000 copies/mL, week-48 snapshot response rates were 80% with DTG/ABC/3TC and 64% with ATV/r/TDF/FTC. Respective 48-week response rates were 86% versus 80% in whites, 74% versus 67% in blacks and 94% versus 56% in other racial/ethnic groups. Snapshot response rates in U.S. participants were 74% with DTG/ABC/3TC and 67% with ATV/r/TDF/FTC. Among participants with a confirmed viral load ≥400 copies/mL on or after week 24, no integrase or protease resistance mutations emerged.
Drug-related adverse events proved less frequent with DTG/ABC/3TC than with ATV/r + TDF/FTC (33% versus 49%), as did serious adverse events (5% versus 8%) and discontinuations due to adverse events (4% versus 7%). Among black women, rates of any adverse event were similar with DTG/ABC/3TC and ATV/r + TDF/FTC (83% and 82%), but among white women, adverse event rates were lower in the DTG/ABC/3TC arm (77% versus 85%).
The ARIA investigators concluded that the virologic superiority of DTG/ABC/3TC to ATV/r + TDF/FTC was driven by both the lower virologic nonresponse rate and fewer discontinuations with the DTG regimen.