PMID- 27774892 OWN - NLM STAT- MEDLINE DCOM- 20180319 LR - 20181220 IS - 1873-4251 (Electronic) IS - 1570-162X (Print) IS - 1570-162X (Linking) VI - 15 IP - 3 DP - 2017 TI - Atazanavir Plus Cobicistat: Week 48 and Week 144 Subgroup Analyses of a Phase 3, Randomized, Double-Blind, Active-Controlled Trial. PG - 216-224 LID - 10.2174/1570162X14666161021102728 [doi] AB - 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-naive 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 (/=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. CI - Copyright(c) Bentham Science Publishers; For any queries, please email at epub@benthamscience.org. FAU - Gallant, Joel AU - Gallant J AD - Southwest CARE Center, 649 Harkle Road, Ste. E, Santa Fe, NM, United States. FAU - Moyle, Graeme AU - Moyle G AD - Chelsea and Westminster Hospital, London, United Kingdom. FAU - Berenguer, Juan AU - Berenguer J AD - Hospital General Universitario Gregorio Maranon, Madrid, Spain. FAU - Shalit, Peter AU - Shalit P AD - Tribal Med, Seattle, WA, United States. FAU - Cao, Huyen AU - Cao H AD - Gilead Sciences, Inc., Foster City, CA, United States. FAU - Liu, Ya-Pei AU - Liu YP AD - Gilead Sciences, Inc., Foster City, CA, United States. FAU - Myers, Joel AU - Myers J AD - Bristol-Myers Squibb, Plainsboro, NJ, United States. FAU - Rosenblatt, Lisa AU - Rosenblatt L AD - Bristol-Myers Squibb, Plainsboro, NJ, United States. FAU - Yang, Lingfeng AU - Yang L AD - Bristol-Myers Squibb, Hopewell, NJ, United States. FAU - Szwarcberg, Javier AU - Szwarcberg J AD - Gilead Sciences, Inc., Foster City, CA, United States. LA - eng SI - ClinicalTrials.gov/NCT01108510 PT - Clinical Trial, Phase III PT - Journal Article PT - Multicenter Study PT - Randomized Controlled Trial PL - Netherlands TA - Curr HIV Res JT - Current HIV research JID - 101156990 RN - 0 (Anti-HIV Agents) RN - 0 (RNA, Viral) RN - 4MT4VIE29P (Atazanavir Sulfate) RN - LW2E03M5PG (Cobicistat) SB - IM MH - Adult MH - Anti-HIV Agents/*administration & dosage/adverse effects MH - Antiretroviral Therapy, Highly Active/adverse effects/*methods MH - Atazanavir Sulfate/*administration & dosage/adverse effects MH - CD4 Lymphocyte Count MH - Cobicistat/*administration & dosage/adverse effects MH - Double-Blind Method MH - Drug-Related Side Effects and Adverse Reactions/epidemiology MH - Female MH - HIV Infections/*drug therapy/virology MH - HIV-1/isolation & purification MH - Humans MH - Male MH - RNA, Viral/blood MH - Sustained Virologic Response MH - Treatment Outcome MH - Withholding Treatment PMC - PMC5543662 OTO - NOTNLM OT - Atazanavir OT - HIV-1 OT - cobicistat OT - pharmacokinetic OT - ritonavir OT - subgroup analysis OT - virologic EDAT- 2016/10/25 06:00 MHDA- 2018/03/20 06:00 PMCR- 2017/08/04 CRDT- 2016/10/25 06:00 PHST- 2016/06/24 00:00 [received] PHST- 2016/09/06 00:00 [revised] PHST- 2016/10/14 00:00 [accepted] PHST- 2016/10/25 06:00 [pubmed] PHST- 2018/03/20 06:00 [medline] PHST- 2016/10/25 06:00 [entrez] PHST- 2017/08/04 00:00 [pmc-release] AID - 79129 [pii] AID - CHIVR-15-216 [pii] AID - 10.2174/1570162X14666161021102728 [doi] PST - ppublish SO - Curr HIV Res. 2017;15(3):216-224. doi: 10.2174/1570162X14666161021102728.