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

Curr HIV Res. 2017;15(3):216-224. doi: 10.2174/1570162X14666161021102728.

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; HIV-1; cobicistat; pharmacokinetic; ritonavir; subgroup analysis; virologic.

Publication types

  • Clinical Trial, Phase III
  • Multicenter Study
  • Randomized Controlled Trial

MeSH terms

  • Adult
  • Anti-HIV Agents / administration & dosage*
  • Anti-HIV Agents / adverse effects
  • Antiretroviral Therapy, Highly Active / adverse effects
  • Antiretroviral Therapy, Highly Active / methods*
  • Atazanavir Sulfate / administration & dosage*
  • Atazanavir Sulfate / adverse effects
  • CD4 Lymphocyte Count
  • Cobicistat / administration & dosage*
  • Cobicistat / adverse effects
  • Double-Blind Method
  • Drug-Related Side Effects and Adverse Reactions / epidemiology
  • Female
  • HIV Infections / drug therapy*
  • HIV Infections / virology
  • HIV-1 / isolation & purification
  • Humans
  • Male
  • RNA, Viral / blood
  • Sustained Virologic Response
  • Treatment Outcome
  • Withholding Treatment

Substances

  • Anti-HIV Agents
  • RNA, Viral
  • Atazanavir Sulfate
  • Cobicistat

Associated data

  • ClinicalTrials.gov/NCT01108510