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Stribild Superior to Boosted Atazanavir in Treatment-Naive Women
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IAS 2015, July 19-22, 2015, Vancouver
Mark Mascolini
Stribild proved virologically superior to atazanavir/ritonavir plus tenofovir/emtricitabine (TDF/FTC) at 48 weeks in WAVES, an international trial in 575 antiretroviral-naive women [1]. No one in the Stribild arm had emergent resistance upon virologic failure, compared with 3 women in the atazanavir arm.
The double-blind WAVES trial recruited antiretroviral-naive women with an estimated glomerular filtration rate (eGFR) at or above 70 mL/min from Europe, Africa, North America, and Asia. All women had a viral load above 500 copies and sensitivity to atazanavir, TDF, and FTC. Researchers randomized 289 women to Stribild (elvitegravir/cobicistat coformulated with TDF/FTC) and 286 to atazanavir/ritonavir plus TDF/FTC. The primary efficacy endpoint was proportion of women with a viral load below 50 copies/mL at week 48 by FDA snapshot analysis.
The largest proportion of women were from Russia (33%), followed by Uganda (28%), the United States (20%), Thailand (4%), Portugal (4%), the UK (3%), and the Dominican Republic (3%). Median age was 34 in the Stribild group and 35 in the atazanavir group. Respective proportions of blacks were 49% and 47%, whites 44% and 42%, and Asians 3% and 6%. Body mass index averaged 26 kg/m2 in both study arms, and three quarters in both arms had a pretreatment viral load below 100,000 copies. Median starting viral load was 4.46 log10 with Stribild and 4.56 with atazanavir (about 29,000 and 36,000 copies); respective median starting CD4 counts were 344 and 370.
Through 48 weeks 29 women (10%) dropped out of the Stribild arm (5 because of adverse events) and 45 (16%) quit the atazanavir arm (19 because of adverse events). Nonadherence accounted for 4 dropouts in the Stribild group and 5 in the atazanavir group. The researchers did not report other adherence findings, a shortcoming since the 3-pill atazanavir regimen could present a steeper adherence challenge than the 1-pill Stribild regimen.
At 48 weeks 87.2% of women randomized to Stribild and 80.8% randomized to atazanavir had a viral load below 50 copies by FDA snapshot analysis. The adjusted difference of 6.5% (95% confidence interval 0.4% to 12.6%) established the 48-week virologic superiority of Stribild in previously untreated women. Sub-50-copy rates among women with a pretreatment viral load above 100,000 copies were 90% with Stribild and 78% with atazanavir. Among women with a pretreatment CD4 count at or below 350, respective sub-50-copy rates were 88% and 82%.
Virologic failure rates were 9% in the Stribild arm and 12% in the atazanavir arm. Virus resistant to study drugs emerged in 3 women with atazanavir virologic failure (all M184V/I) and in no women with Stribild virologic failure. CD4 counts rose by similar amounts in both study arms.
Adverse events leading to study drug discontinuation numbered 5 in the Stribild group and 19 in the atazanavir group. Through 48 weeks eGFR declined by a median of 6.1 mL/min in the Stribild arm and 2.4 mL/min in the atazanavir arm, a nonsignificant difference (P = 0.15). Hip and spine bone mineral density each fell by about 3% through 48 weeks in both study arms. Total cholesterol rose significantly more with Stribild than with atazanavir (P = 0.02), but 48-week changes in LDL cholesterol, HDL cholesterol, total-to-HDL ratio, and triglycerides did not differ significantly between groups.
Reference
1. Squires K, Kityo C, Hodder S, et al. Elvitegravir (EVG) / cobicistat (COBI) / emtricitabine (FTC)/ tenofovir disoproxil fumarate (TDF) is superior to ritonavir (RTV) boosted atazanavir (ATV) plus FTC/TDF in treatment naive women with HIV-1 infection (WAVES Study). IAS 2015. 8th Conference on HIV Pathogenesis, Treatment and Prevention. July 19-22, 2015. Vancouver. Abstract MOLBPE08.
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