Evaluation of efficacy, safety, pharmacokinetics, and adherence in HIV-1-infected, antiretroviral-naïve patients treated with ritonavir-boosted atazanavir plus fixed-dose tenofovir DF/emtricitabine given once daily

HIV Clin Trials. 2008 Jul-Aug;9(4):213-24. doi: 10.1310/hct0904-213.

Abstract

Objectives: Evaluate efficacy, safety, tolerability, pharmacokinetics, adherence, and treatment satisfaction of atazanavir/ritonavir (ATV/r) 300 mg/100mg and tenofovir DF/emtricitabine (TDF/FTC) 300 mg/200mg once daily in antiretroviral-naïve HIV-infected patients.

Method: Single-arm, open-label, multicenter 48-week study.

Results: 100 patients were evaluated; 17 patients discontinued early including 6 for adverse events. There were 2 deaths (multi-organ failure, lactic acidosis). At 48 weeks, 81% achieved HIV-1 RNA <50 copies/mL (ITT, M=F). No K65R or ATV/r associated mutations emerged; M184V developed in one patient. Median CD4 increase was 217 cells/mm3. The most common adverse events (> or = 10%) were diarrhea, nausea, scleral icterus, fatigue, upper respiratory tract infection, headache, and vomiting. Grade 4 hyperbilirubinemia occurred in 5%. Median increases at 48 weeks in total cholesterol, HDL, LDL, and triglycerides were 11, 3, 2, and 5 mg/dL, respectively. Two patients had confirmed graded increases in serum creatinine (one grade 1, one grade 2). Median (IQR) creatinine clearance change from baseline at 48 weeks was -7 (-19, 2) mL/min. Geometric mean (95% CI) ATV trough concentrations exceeded suggested therapeutic range. At 48 weeks, 92% of patients reported complete adherence by 1-week recall and 90% reported being "very satisfied" with the regimen.

Conclusion: ATV/r+TDF/FTC was safe, well tolerated, and convenient for patients. Larger comparative trials are ongoing.

Publication types

  • Clinical Trial
  • Multicenter Study

MeSH terms

  • Adenine / adverse effects
  • Adenine / analogs & derivatives*
  • Adenine / pharmacokinetics
  • Adenine / therapeutic use
  • Adult
  • Aged
  • Anti-HIV Agents* / adverse effects
  • Anti-HIV Agents* / pharmacokinetics
  • Anti-HIV Agents* / therapeutic use
  • Antiretroviral Therapy, Highly Active
  • Atazanavir Sulfate
  • Creatinine / blood
  • Deoxycytidine / adverse effects
  • Deoxycytidine / analogs & derivatives*
  • Deoxycytidine / pharmacokinetics
  • Deoxycytidine / therapeutic use
  • Diarrhea / etiology
  • Drug Administration Schedule
  • Emtricitabine
  • Fatigue / etiology
  • Female
  • HIV Infections / blood
  • HIV Infections / drug therapy*
  • HIV Infections / metabolism*
  • HIV-1*
  • Humans
  • Hyperbilirubinemia
  • Jaundice / etiology
  • Male
  • Middle Aged
  • Nausea / etiology
  • Oligopeptides* / adverse effects
  • Oligopeptides* / pharmacokinetics
  • Oligopeptides* / therapeutic use
  • Organophosphonates* / adverse effects
  • Organophosphonates* / pharmacokinetics
  • Organophosphonates* / therapeutic use
  • Patient Compliance
  • Pyridines* / adverse effects
  • Pyridines* / pharmacokinetics
  • Pyridines* / therapeutic use
  • Respiratory Tract Infections / etiology
  • Ritonavir* / pharmacokinetics
  • Ritonavir* / therapeutic use
  • Tenofovir
  • Treatment Outcome
  • United States

Substances

  • Anti-HIV Agents
  • Oligopeptides
  • Organophosphonates
  • Pyridines
  • Deoxycytidine
  • Atazanavir Sulfate
  • Tenofovir
  • Creatinine
  • Emtricitabine
  • Adenine
  • Ritonavir