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

Abstract

Objectives: Evaluate efficacy, safety, tolerability, pharmacokinetics, adherence, and treatment satisfaction of atazanavir/ritonavir (ATV/r) 300mg/100mg and tenofovir DF/emtricitabine (TDF/FTC) 300mg/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 (≥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. © 2008 Thomas Land Publishers, Inc.