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Atazanavir Plus Cobicistat: Week 48 and Week 144 Subgroup Analyses of a Phase 3, Randomized, Double-Blind, Active-Controlled Trial

[ Vol. 15 , Issue. 3 ]

Author(s):

Joel Gallant, Graeme Moyle, Juan Berenguer, Peter Shalit, Huyen Cao, Ya-Pei Liu, Joel Myers, Lisa Rosenblatt, Lingfeng Yang and Javier Szwarcberg   Pages 216 - 224 ( 9 )

Abstract:


Objectives: Cobicistat (COBI) enhances atazanavir (ATV) pharmacokinetic parameters similarly to ritonavir (RTV) in both healthy volunteers and HIV-infected adults. Primary efficacy and safety outcomes of this Phase 3, international, randomized, double-blind, double-dummy, active- controlled trial in HIV-1-infected treatment-naïve adults (GS-US-216-0114/NCT01108510) demonstrated that ATV+COBI was non-inferior to ATV+RTV, each in combination with emtricitabine/ tenofovir disoproxil fumarate (FTC/TDF), at Weeks 48 and 144, with high rates of virologic success for both regimens (85.2% and 87.4%, respectively, at Week 48; and 72.1% and 74.1% at Week 144), and with comparable safety and tolerability. Here, we describe virologic response and treatment discontinuation by a wider range of subgroups than previously presented.

Methods: Subgroup analyses by baseline CD4 count (≤200, 201-350, >350 cells/mm3), baseline HIV-1 RNA level (≤100,000, >100,000 copies/mL), race, sex, and age (<40, ≥40 years) evaluated ATV+COBI versus ATV+RTV univariate odds ratios (ORs) for virologic success (viral load <50 copies/mL, intention-to-treat US Food and Drug Administration Snapshot algorithm) and discontinuation due to adverse events (AEs) at Weeks 48 and 144. Of 692 patients randomized, 344 received ATV+COBI and 348 ATV+RTV.

Results: ATV+COBI versus ATV+RTV ORs for virologic success did not significantly differ by regimen overall at Weeks 48 and 144 (OR 0.90; 95% confidence interval [CI]: 0.64, 1.26) or within subgroups, except in females, for whom ATV+COBI was favored at Week 144 (OR 2.36; 95% CI: 1.02, 5.47). However, there were more discontinuations due to withdrawal of consent and pregnancies in females receiving ATV+RTV versus ATV+COBI. ORs for discontinuation due to AEs did not significantly differ by regimen overall at Weeks 48 and 144 (OR 0.98; 95% CI: 0.61, 1.58) or within subgroups.

Conclusion: These findings indicate that both ATV+COBI and ATV+RTV, each with FTC/TDF, are effective and well-tolerated treatment options across a wide demographic range of HIV-infected patients.

Keywords:

Atazanavir, cobicistat, ritonavir, subgroup analysis, HIV-1, pharmacokinetic, virologic.

Affiliation:

Southwest CARE Center, 649 Harkle Road, Ste. E, Santa Fe, NM, Chelsea and Westminster Hospital, London, Hospital General Universitario Gregorio Maranon, Madrid, Tribal Med, Seattle, WA, Gilead Sciences, Inc., Foster City, CA, Gilead Sciences, Inc., Foster City, CA, Bristol-Myers Squibb, Plainsboro, NJ, Bristol-Myers Squibb, Plainsboro, NJ, Bristol-Myers Squibb, Hopewell, NJ, Gilead Sciences, Inc., Foster City, CA



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