An ART regimen consisting of once-daily Stribild may be safer and more effective in women with HIV-1 infection than the standard multidrug combination treatment, according to a study presented at ICAAC 2015. Healio reports that this is the first ART study to exclusively enrol women, and its results contrasted with those of a previous study of the drug which enrolled mostly men, according to Dr Sally Hodder, director of the West Virginia Clinical and Translational Science Institute.
“Historically, we’ve accepted 10% women in clinical trials,” Hodder said during a press event. “Regulatory agencies have made decisions based on very small populations of women, but obviously their approval is for the whole population. It’s really important to have this trial … I think it’s really a milestone because it was enrolling all women.”
In the international, randomised, double blind WAVES study, Hodder and colleagues evaluated the safety and efficacy of a single tablet of Stribild (elvitegravir/cobicistat/emtricitabine/tenofovir disoproxil fumarate, Gilead Sciences; EVG/COBI/FTC/TDF) among a cohort of women with HIV and no history of ART. A total of 575 participants from Africa, Asia, Europe, Latin America and North America were enrolled in the study, half of whom were randomly assigned daily EVG/COBI/FTC/TDF and half assigned a combination treatment comprising Norvir (ritonavir, AbbVie; RTV)-boosted Reyataz (atazanavir, Bristol-Myers Squibb; ATV) plus FTC/TDF (RTV+ATV+FTC/TDF). Efficacy was determined by the proportion of participants who achieved HIV-1 RNA fewer than 50 cells/mL at week 48, and subgroup analyses were performed by region.
Baseline characteristics were comparable across all regions. The median age of participants was 35 years; approximately half were black (48%). Most reported unprotected heterosexual intercourse as the source of their infection. At week 48, EVG/COBI/FTC/TDF was associated with an 87.2% rate of viral suppression, as opposed to an 80.8% rate among those given RTV+ATV+FTC/TDF (adjusted difference = 6.5%; 95% CI, 0.4%-12.6%). Virologic response to both regimens was greatest in Uganda and lowest in the US, and according to Hodder, it was well correlated to adherence in these regions.
Virologic failure associated with the development of resistance was not seen among participants given EVG/COBI/FTC/TDF, although there were three such cases reported in the RTV+ATV+FTC/TDF arm. In addition, discontinuations due to adverse events were more frequent among those given RTV+ATV+FTC/TDF (19 vs. 5).
According to Hodder, results that prove the efficacy of a single-tablet treatment is especially important in light of the stigma facing many women with HIV.
Background: Women are under-represented in HIV antiretroviral therapy (ART) studies. The Women AntiretroViral Efficacy and Safety study (WAVES) is the first all-women, international, randomized, double-blind, phase 3 trial designed to evaluate the safety and efficacy of EVG/COBI/FTC/TDF versus ATV+RTV+FTC/TDF.
Methods: HIV 1 infected, ART naïve women were randomized (1:1), in a double-blind, global study (North America, Europe, Africa, Asia). Entry criteria included HIV RNA>500 copies(c)/mL and estimated GFR≥ 70 mL/min. Women who become pregnant had the option to continue on study drug. The primary efficacy endpoint was the proportion of women achieving a HIV 1 RNA < 50 c/mL at Week 48. Safety was assessed throughout the study.
Results: 575 women were enrolled (EVG/COBI/FTC/TDF, n=289 vs ATV+RTV+FTC/TDF, n= 286). Demographic and baseline characteristics were balanced and reflect the global nature of the study (Table 1). The median age was 35 years and 78% had asymptomatic HIV infection. EVG/COBI/FTC/TDF was statistically superior to ATV+RTV+FTC/TDF, with 87.2% and 80.8%, respectively, achieving HIV-1RNA < 50 c/mL at week 48 (adjusted difference 6.5%, 95% CI 0.4% to 12.6%). Mean increases in CD4 cell counts were similar (Table 1). No subject experienced virologic failure with resistance in the EVG/COBI/FTC/TDF arm, compared to 3 (1%) in the ATV+RTV+FTC/TDF arm (M184V/I). Both regimens were generally well tolerated, with most adverse events being mild (grade 1) in severity. Mean decreases in eGFR were small and similar at week 48 (-4.5 vs -2.3 mL/min, p=0.15) with no discontinuations due to renal adverse events (AEs) in the EVG/COBI/FTC/TDF arm. Percent changes in BMD at week 48 were similar at spine (-3•09 vs -3.26, p=0.69) and hip (-3.02 vs -2•55, p=0•37). Of the 24 pregnancies reported, 13 women elected to continue study drugs.
Conclusions: EVG/COBI/FTC/TDF was superior to ATV+RTV+FTC/TDF at 48 week, and demonstrated its safety and efficacy for the treatment HIV 1 infection in women. Recruitment, enrollment and retention of women in large multinational trials is feasible.