XIX International AIDS Conference


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TUAB0103 - Oral Abstract

Cobicistat versus ritonavir as pharmacoenhancers in combination with atazanavir plus tenofovir disoproxil fumarate/emtricitabine: phase 3 randomized, double blind, active-controlled trial, week 48 results

Presented by Joel Gallant (United States).

J. Gallant1, E. Koenig2, J. Andrade-Villanueva3, P. Chetchotisakd4, E. DeJesus5, F. Antunes6, K. Arastéh7, G. Moyle8, G. Rizzardini9, J. Fehr10, Y.-P. Liu11, L. Zhong11, C. Callebaut11, S. Ramanathan11, J. Szwarcberg11, M. Rhee11, A. Cheng11

1Johns Hopkins School of Medicine, Baltimore, United States, 2Instituto Dominicano de Estudios Virologicos -IDEV-, Santo Domingo, Dominican Republic, 3Hospital Civil, Guadalajara, Mexico, 4Khon Kaen University, Muang District, Thailand, 5Orlando Immunology Center, Orlando, United States, 6Hospital de Santa Maria, Lisboa, Portugal, 7EPIMED / Vivantes Auguste-Viktoria-Klinikum, Berlin, Germany, 8Chelsea & Westminster Hospital, London, United Kingdom, 9Ospedale Luigi Sacco, Milano, Italy, 10University Hospital Zurich, Zurich, Switzerland, 11Gilead Sciences, Foster City, United States

Background: Cobicistat is a novel investigational pharmacoenhancer with no anti-HIV activity.
Methods: An international, randomized, double-blind, double-dummy, active controlled trial was conducted to evaluate the efficacy and safety of cobicistat vs ritonavir as pharmacoenhancers of atazanavir (ATV/co vs ATV/r group) in combination with tenofovir disoproxil fumarate (TDF)/emtricitabine (FTC) in treatment-naïve patients. Key eligibility criteria were HIV-1 RNA ≥ 5,000 copies/mL, estimated glomerular filtration rate by Cockcroft-Gault formula (eGFR) ≥ 70 mL/min. Primary endpoint was HIV-1 RNA < 50 copies/mL at Week 48 by snapshot algorithm, and noninferiority margin was -12%.
Results: A total of 692 subjects were randomized and received at least 1 dose of study drug (344 in ATV/co group and 348 in ATV/r group) (Table 1). At Week 48, virologic success was achieved in 85% (ATV/co) and 87% (ATV/r) (difference: −2.2%; 95% CI: −7.4 to 3.0) (Table 2); among subjects with HIV-1 RNA > 100,000 copies/mL, the response rates were similar (86 vs 86%). Two subjects in ATV/co and none in ATV/r group developed resistance mutations to study drugs; both were M184V/I. Similar percentages of subjects in both groups (ATV/co vs ATV/r) had serious adverse events (AEs) (11 vs 7%), discontinued study drug due to any AEs (7 vs 7%), or had bilirubin-related AEs (4 vs 3%). Median increases in total bilirubin at Week 48 in ATV/co and ATV/r group were 1.9 and 1.7 mg/dL. Median increases in serum creatinine were 0.13 and 0.09 mg/dL. Median increases in total cholesterol were 4 and 10 mg/dL; increases in triglycerides were 16 and 24 mg/dL. Plasma exposures of ATV (steady state mean Ctau [ng/mL]) were comparable (796.1 vs 853.4).
Conclusions: ATV/co was noninferior to ATV/r in combination with TDF/FTC at Week 48. Both regimens achieved high rates of virologic success. Safety and tolerability profiles of the two regimens were comparable.

 ATV/co (n=344)ATV/r (n=348)
Age (years), median3637
Race - White58%62%
HIV-1 RNA (log10copies/mL), median4.784.84
HIV-1 RNA > 100,000 copies/mL38%41%
CD4 count (cells/mm3), median348341
CD4 count ≤ 200 cells/ mm317%16%
[Baseline Characteristics]

 ATV/co (n=344)ATV/r (n=348)
Snapshot Analysis85%87%
Snapshot Analysis (Per Protocol)98%98%
Time to Loss of Virologic Response83%85%
[Efficacy at Week 48 (HIV-1 RNA < 50 copies/mL)]

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