Elvitegravir (EVG) / cobicistat (COBI) / emtricitabine (FTC)/ tenofovir disoproxil fumarate (TDF) is superior to ritonavir (RTV) boosted atazanavir (ATV) plus FTC/TDF in treatment naïve women with HIV-1 infection (WAVES Study)
Presented by Kathleen Squires
K. Squires1, C. Kityo2, S. Hodder3, D. Hagins4, A. Avihingsanon5, Y. Plotnikova6, E. Koenig7, F. Post8, K. White9, S.-S. Chen9, H. Cao9, A. Cheng10, J. Szwarcberg10, WAVES Study Investigators
1Thomas Jefferson University, Medicine, Philadelphia, United States, 2Joint Clinical Research Centre, Kampala, Uganda, 3West Virginia Clinical and Translational Science Institute, Morgantown, United States, 4Chatham County Health Department, Savannah, United States, 5Thai Red Cross AIDS Rsch Ctr, Bangkok, Thailand, 6GUZ Irkutsk Reg.Cter Prevent, Irkutsk, Russian Federation, 7Zona Universitaria/, IDEV, Santo Domingo, Dominican Republic, 8Kings College London, London, United Kingdom, 9Gilead Sciences, Inc., Foster City, United States, 10Gilead Sciences, Foster City, United States
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.