AT AIDS 2016
DURBAN, SOUTH AFRICA (FRONTLINE MEDICAL NEWS) – A novel single-tablet, triple-antiretroviral combination regimen outperformed the well-established combination of ritonavir-boosted atazanavir plus tenofovir/emtricitabine in the ARIA trial, a phase IIIb study conducted in treatment-naive women with HIV infection.
The fixed-dose once-daily combination of dolutegravir 50 mg/abacavir 600 mg/lamivudine 300 mg, marketed in the United States as Triumeq since its approval in 2014, showed superior efficacy and a more favorable safety profile than did ritonavir-boosted atazanavir (Reyataz) plus tenofovir/emtricitabine (Truvada), Catherine Orrell, MD, reported at the 21st International AIDS Conference.
ARIA was a 48-week open-label randomized trial involving 495 treatment-naive HIV-infected women in the United States and 11 other countries. The primary endpoint – a plasma HIV RNA viral load below 50 copies/mL after 48 weeks of treatment – was achieved in 82% of patients on dolutegravir/abacavir/lamivudine (DTG/ABC/3TC), compared with 71% on ritonavir-boosted atazanavir plus tenofovir/emtricitabine (ATV+RTV+FTC/TDF).
Of note, the difference in efficacy was even more pronounced among women with a baseline viral load in excess of 100,000 copies/mL: an 80% success rate in attaining a viral load of less than 50 copies/mL at 48 weeks in the DTG/ABC/3TC group, compared with 64% in the comparator arm. Women with this baseline massive viral load comprised 28% of study participants, added Dr. Orrell of the University of Cape Town, South Africa.
To be eligible for the study, women had to be negative for an HLA-B*5701 genetic screen for allergic hypersensitivity to abacavir.
A particularly attractive feature of DTG/ABC/3TC is that dolutegravir, an unboosted integrin strand transfer inhibitor, provides a high barrier to development of drug resistance. Indeed, no subjects in the dolutegravir arm developed treatment-emergent primary integrin strand transfer inhibitor or abacavir/lamivudine resistance mutations, according to Dr. Orrell.
The superior efficacy of the single-tablet regimen was driven in part by fewer discontinuations due to adverse events: a 4% rate versus 7% in the comparator arm. Another key factor was the substantially lower virologic failure rate in DTG/ABC/3TC-treated women: 6% versus 14% in the comparator arm.
The single-tablet regimen also had a better safety profile. The combined rate of the most common drug-related adverse events – nausea, diarrhea, headache, and jaundice – was 22% in the DTG/ABC/3TC group compared with 38% with ATV+RTV+FTC/TDF.
The incidence of treatment-emergent psychiatric events – insomnia, anxiety, depression, or suicidal ideation – was roughly 14% in each treatment arm. That’s an important finding because some other studies have found an increase in psychiatric events in patients receiving integrin strand transfer inhibitors.
“The overall results, I think, are important for the field,” Kimberly Smith, MD, said at a press conference highlighting the ARIA trial.
“Women are often underrepresented in HIV clinical trials even though they bear much of the burden of the HIV epidemic,” added Dr. Smith, vice president for global medical strategy and head of research and development at ViiV Healthcare in Research Triangle Park, N.C.
“This fixed-dose combination is a winner,” said Salim Abdool Karim, MD, director of the Center for the AIDS Program of Research in South Africa, Durban, who chaired the press conference.
Dr. Orrell received a research grant from ViiV Healthcare, which sponsored the ARIA study.