The primary endpoint was the proportion of patients with an undetectable HIV RNA level (<50 copies/mL) at 48 weeks in the intention to treat population using the Food and Drug Administration (FDA) snapshot analysis.
In both studies, Seliciclib mouse Stribild was non-inferior to the comparator and associated with high rates (84–87%) of HIV RNA Selleckchem RG-7388 suppression throughout 96 weeks, low rates (2–3%) of treatment-emergent NRTI/II resistance, and less dizziness or abnormal dreams (vs. EFV) and diarrhoea (vs. ATV/RTV) (Table 3). The GS-US-216-0114 study is an ongoing phase III, double-blind, randomised, placebo-controlled trial of antiretroviral-naïve HIV-1-positive adults (n = 692) with baseline HIV RNA measurements of >5,000 copies/mL and creatinine clearance ≥70 mL/min who were randomised 1:1 to COBI 150 mg or RTV 100 mg, each given together with ATV 300 mg and TDF/FTC once daily [33]. At 48 weeks, the COBI/ATV regimen was non-inferior to the RTV/ATV regimen, with 85% and 87% of patients achieving HIV RNA <50 copies/mL, respectively. Adverse events, including bilirubin elevations, jaundice, nausea and diarrhoea, and study drug discontinuations due to adverse events occurred with equal frequency in both arms [33]. Other ongoing studies investigate a switch from TDF/FTC plus an NNRTI to Stribild (ClinicalTrials.gov identifier: NCT01495702) or TDF/FTC plus a RTV-boosted PI to Stribild (ClinicalTrials.gov identifier: NCT01495702),
and the use of Stribild or COBI in patients MK5108 with impaired renal function (creatinine clearance 50–89 mL/min; ClinicalTrials.gov identifier: NCT01363011). A small single-arm study confirmed the safety of a switch from TDF/FTC plus RTG to Stribild [34]. Table 3 Phase III trials of cobicistat-containing combination antiretroviral therapy regimens in treatment-naïve individuals Study Population Treatment Results Comments GS-US-0102 [28, 30] N = 700, 89% male, median age 38, CD4
380 cells/mm3, VL 4.75 log copies/mL Stribild vs. Atripla (randomised 1:1, double-blind) Stribild vs. Atripla (48w): HIV RNA Endonuclease <50 copies/mL: 87.6% vs. 84.1% (difference 3.6%, 95% CI −1.6 to 8.8%) CD4 increases: 239 vs. 209 cells/mm3, p = 0.009 Virological failure: 14 (4%) vs. 17 (5%); 2% developed II and 2% NRTI resistance vs. 2% NNRTI and 1% NRTI mutations Fasting lipids: smaller increases with Stribild (p = 0.001) Treatment-emergent adverse events leading to discontinuation: 4% vs. 5% Dizziness and abnormal dreams: 24–27% vs 7–15% Diarrhoea and nausea were equally common in both arms (14–23%) Stribild non-inferior to Atripla Trend for better viral responses on Stribild for low (<100,000 copies/mL) and high baseline HIV RNA At 96 weeks, non-inferiority in terms of viral suppression (84% vs. 82%, difference 2.7%, 95% CI −2.9 to 8.3%) was maintained, with emergent resistance observed in 3% of patients in each arm GS-US-0103 [29, 31] N = 708, 90% male, median age 38, CD4 360 cells/mm3 VL 4.8 log copies/mL Stribilid vs.