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.

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.

Tenofovir DF plus lamivudine or emtricitabine for nonoccupational postexposure prophylaxis (NPEP) in a Boston Community Health Center.

BACKGROUND: Nonoccupational postexposure prophylaxis (NPEP) has been used to decrease HIV transmission after high-risk exposures. However, suboptimal adherence in completing the recommended 28-day course has resulted in prophylaxis failures. Fenway Community Health, the largest center caring for HIV-infected and high-risk men who have sex with men (MSM) in New England, began an NPEP program in 1997, initially using zidovudine-based regimens. METHODS: Two phase 4 studies, using tenofovir DF regimens combined with either lamivudine or emtricitabine, were conducted. This paper evaluates the experience of those who used tenofovir-based NPEP regimens, comparing the subjects to historical controls who used zidovudine-containing regimens. RESULTS: Between May 2004 and March 2005, 44 individuals who presented after high-risk sexual exposure were prescribed tenofovir DF/lamivudine for NPEP. Between March 2005 and March 2006, 68 individuals with 72 high-risk experiences received tenofovir DF/emtricitabine, and were compared to122 historical controls who were prescribed 126 courses of zidovudine plus lamivudine between January 2000 and May 2004. Seventy-two percent of those who took tenofovir DF and emtricitabine, and 87.5% of the participants who took tenofovir DF and lamivudine, for NPEP completed their regimens as prescribed, whereas only 42.1% of those who took zidovudine plus lamivudine did so (P < 0.0001). Participants who took tenofovir DF-containing regimens were more likely to report diarrhea or abdominal discomfort; patients who took zidovudine-containing regimens were more likely to report nausea and vomiting, which was often severe enough to lead to product discontinuation. CONCLUSIONS: Tenofovir DF-containing regimens for NPEP are generally well tolerated with high completion rates. Tolerability and adherence compared favorably to zidovudine-containing regimens used previously. Tenofovir DF-containing regimens should be considered for PEP to enhance adherence and regimen completion.

Pharmacokinetic evaluation and short-term activity of stavudine, nevirapine, and nelfinavir therapy in HIV-1-infected adults.

OBJECTIVE: Evaluate pharmacokinetic interaction, short-term safety, and antiretroviral activity of stavudine (d4T), nevirapine (NVP), and nelfinavir (NFV) as combination HIV-1 therapy. DESIGN: Prospective, open-label study investigating the pharmacokinetic interactions between d4T, NVP, and NFV and documenting short-term tolerability and virologic and immunologic activity. METHODS: Twenty-five HIV-1-infected adults, naive to nonnucleoside reverse transcriptase inhibitors (NNRTIs) and protease inhibitors (PIs), < or = 6 months of d4T treatment, CD4 > or = 100 cells/mm, and viral load > = 5,000 copies/mL enrolled. All received NFV 750 mg 3 times daily and d4T 30-40 mg twice daily for 1 week, then added NVP at 200 mg once daily for 2 weeks and 200 mg twice daily thereafter. Steady-state pharmacokinetic parameters of NFV, AG1402 (metabolite of NFV), and d4T were compared before and after the addition of NVP. RESULTS: No statistically significant changes in NFV or d4T pharmacokinetics were observed following the addition of NVP. Levels of AG1402 were suppressed 60-70%. Drug-related adverse events were seen at expected rates. At day 36, median viral load suppression was 2.0 log10 and absolute CD4 count increased by 111 cells/mm. CONCLUSIONS: NVP administration did not significantly affect the steady-state pharmacokinetic parameters of NFV or d4T. The combination of d4T, NVP, and NFV induced rapid suppression of HIV-1 viral load and rises in CD4 cell count.