OBJECTIVE: To assess efficacy and safety of cobicistat versus ritonavir as pharmacoenhancers for atazanavir when administered with emtricitabine/tenofovir df as initial treatment for HIV-1 infection. DESIGN: Randomized, partially placebo-controlled, double-blind, multicenter study. PARTICIPANTS: Antiretroviral treatment-naive adults, screening HIV-1 RNA of at least 5000 copies/ml and CD4 cell count more than 50 cells/μl. INTERVENTION: Randomized 2 : 1 (stratified by HIV RNA ≤ or >100,000 copies/ml) to receive placebo-blinded once-daily cobicistat 150 mg or ritonavir 100 mg with open-label atazanavir and fixed-dose emtricitabine/tenofovir df. MAIN OUTCOME MEASURES: Efficacy and safety at weeks 24 and 48. RESULTS: Eighty-four percent of ATV/co participants and 86% of ATV/r participants suppressed HIV-1 RNA (<50 copies/ ml) at week 24, and 82 and 86% at week 48, respectively, and mean CD4 cell count increased 203 and 199 cells/μl at week 24 and 208 and 177 cells/μl at week 48, respectively. Study treatment discontinuation due to adverse events occurred in 4% ATV/co and in 3% ATV/r participants through 48 weeks. Treatment-related adverse events occurred in 36% ATV/co and 48% ATV/r participants; hyperbilirubinemia occurred in 96 and 100%, and ocular icterus or jaundice occurred in 14 and 17%, respectively. Mean estimated glomerular filtration rate (Cockcroft-Gault, ml/min) decrease occurred in both treatment groups and was evident at week 2 (ATV/co -9, ATV/r -4), reached a nadir by week 24 (-15, -14, respectively), and did not progress further through week 48 (-13, -14). CONCLUSION: Using cobicistat and ritonavir as pharmacoenhancers for atazanavir and administered with emtricitabine/tenofovir df achieved comparable rates of virologic suppression and CD4 cell count increase with satisfactory safety profiles.
RCT Entities:
OBJECTIVE: To assess efficacy and safety of cobicistat versus ritonavir as pharmacoenhancers for atazanavir when administered with emtricitabine/tenofovir df as initial treatment for HIV-1 infection. DESIGN: Randomized, partially placebo-controlled, double-blind, multicenter study. PARTICIPANTS: Antiretroviral treatment-naive adults, screening HIV-1 RNA of at least 5000 copies/ml and CD4 cell count more than 50 cells/μl. INTERVENTION: Randomized 2 : 1 (stratified by HIV RNA ≤ or >100,000 copies/ml) to receive placebo-blinded once-daily cobicistat 150 mg or ritonavir 100 mg with open-label atazanavir and fixed-dose emtricitabine/tenofovir df. MAIN OUTCOME MEASURES: Efficacy and safety at weeks 24 and 48. RESULTS: Eighty-four percent of ATV/coparticipants and 86% of ATV/rparticipants suppressed HIV-1 RNA (<50 copies/ ml) at week 24, and 82 and 86% at week 48, respectively, and mean CD4 cell count increased 203 and 199 cells/μl at week 24 and 208 and 177 cells/μl at week 48, respectively. Study treatment discontinuation due to adverse events occurred in 4% ATV/co and in 3% ATV/rparticipants through 48 weeks. Treatment-related adverse events occurred in 36% ATV/co and 48% ATV/rparticipants; hyperbilirubinemia occurred in 96 and 100%, and ocular icterus or jaundice occurred in 14 and 17%, respectively. Mean estimated glomerular filtration rate (Cockcroft-Gault, ml/min) decrease occurred in both treatment groups and was evident at week 2 (ATV/co -9, ATV/r -4), reached a nadir by week 24 (-15, -14, respectively), and did not progress further through week 48 (-13, -14). CONCLUSION: Using cobicistat and ritonavir as pharmacoenhancers for atazanavir and administered with emtricitabine/tenofovir df achieved comparable rates of virologic suppression and CD4 cell count increase with satisfactory safety profiles.
Authors: Parag Kumar; Lori A Gordon; Kristina M Brooks; Jomy M George; Anela Kellogg; Maryellen McManus; Raul M Alfaro; Khanh Nghiem; Jay Lozier; Colleen Hadigan; Scott R Penzak Journal: Antimicrob Agents Chemother Date: 2017-10-24 Impact factor: 5.191
Authors: Jeffrey L Lennox; Raphael J Landovitz; Heather J Ribaudo; Ighovwerha Ofotokun; Lumine H Na; Catherine Godfrey; Daniel R Kuritzkes; Manish Sagar; Todd T Brown; Susan E Cohn; Grace A McComsey; Francesca Aweeka; Carl J Fichtenbaum; Rachel M Presti; Susan L Koletar; David W Haas; Kristine B Patterson; Constance A Benson; Bryan P Baugh; Randi Y Leavitt; James F Rooney; Daniel Seekins; Judith S Currier Journal: Ann Intern Med Date: 2014-10-07 Impact factor: 25.391