title: Atazanavir Plus Cobicistat: Week 48 and Week 144 Subgroup Analyses of a Phase 3, Randomized, Double-Blind, Active-Controlled Trial.
abstract: 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.
  
  
  
  Subgroup analyses by baseline CD4 count (≤200, 201-350, &gt;350 cells/mm3), baseline HIV-1 RNA level (≤100,000, &gt;100,000 copies/mL), race, sex, and age (&lt;40, ≥40 years) evaluated ATV+COBI versus ATV+RTV univariate odds ratios (ORs) for virologic success (viral load &lt;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.
  
  
  
  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.
  
  
  
  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.
authors: Southwest CARE Center, 649 Harkle Road, Ste. E, Santa Fe, NM, United States.
authors: Joel
authors: J
authors: Gallant
authors: Chelsea and Westminster Hospital, London, United Kingdom.
authors: Graeme
authors: G
authors: Moyle
authors: Hospital General Universitario Gregorio Maranon, Madrid, Spain.
authors: Juan
authors: J
authors: Berenguer
authors: Tribal Med, Seattle, WA, United States.
authors: Peter
authors: P
authors: Shalit
authors: Gilead Sciences, Inc., Foster City, CA, United States.
authors: Huyen
authors: H
authors: Cao
authors: Gilead Sciences, Inc., Foster City, CA, United States.
authors: Ya-Pei
authors: YP
authors: Liu
authors: Bristol-Myers Squibb, Plainsboro, NJ, United States.
authors: Joel
authors: J
authors: Myers
authors: Bristol-Myers Squibb, Plainsboro, NJ, United States.
authors: Lisa
authors: L
authors: Rosenblatt
authors: Bristol-Myers Squibb, Hopewell, NJ, United States.
authors: Lingfeng
authors: L
authors: Yang
authors: Gilead Sciences, Inc., Foster City, CA, United States.
authors: Javier
authors: J
authors: Szwarcberg
mesh_terms: D000328:Adult; D019380:Anti-HIV Agents / Q000008:administration & dosage* / Q000009:adverse effects; D023241:Antiretroviral Therapy, Highly Active / Q000009:adverse effects / Q000379:methods*; D000069446:Atazanavir Sulfate / Q000008:administration & dosage* / Q000009:adverse effects; D018791:CD4 Lymphocyte Count; D000069547:Cobicistat / Q000008:administration & dosage* / Q000009:adverse effects; D004311:Double-Blind Method; D064420:Drug-Related Side Effects and Adverse Reactions / Q000453:epidemiology; D005260:Female; D015658:HIV Infections / Q000188:drug therapy* / Q000821:virology; D015497:HIV-1 / Q000302:isolation & purification; D006801:Humans; D008297:Male; D012367:RNA, Viral / Q000097:blood; D000072230:Sustained Virologic Response; D016896:Treatment Outcome; D028761:Withholding Treatment
chemical_list: D019380:Anti-HIV Agents; D012367:RNA, Viral; D000069446:Atazanavir Sulfate; D000069547:Cobicistat
keywords: Atazanavir; HIV-1; cobicistat; pharmacokinetic; ritonavir; subgroup analysis; virologic