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 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.
Single-arm, open-label, multicenter 48-week study.
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.
ATV/r+TDF/FTC was safe, well tolerated, and convenient for patients. Larger comparative trials are ongoing.
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ABSTRACT: Emtricitabine, a nucleoside reverse transcriptase inhibitor (RTI), and tenofovir disoproxil fumarate (tenofovir DF), a nucleotide RTI, as a fixed-dose combination tablet (emtricitabine/tenofovir DF) for once-daily oral administration, are used as the nucleoside/nucleotide RTI backbone in combination with other antiretroviral agents, including ritonavir-boosted protease inhibitors (PIs), in the treatment of adults with HIV-1 infection. Emtricitabine and tenofovir DF show good activity against laboratory strains and clinical isolates of HIV-1 in vitro, although strains with resistance to emtricitabine or tenofovir have also been reported. Regimens consisting of once-daily emtricitabine/tenofovir DF 200 mg/300 mg plus lopinavir/ritonavir (in the randomized, double-blind, placebo-matched, multicentre HEAT study) or boosted atazanavir or efavirenz (in the randomized, partially-blind, multicentre ACTG 5202 trial) were effective in the initial treatment of patients with HIV-1 infection (with screening plasma HIV-1 RNA levels of >or=100,000 copies/mL in ACTG 5202). In other randomized studies, emtricitabine/tenofovir DF 200 mg/300 mg once daily was an effective backbone for boosted PI-based regimens in the initial treatment of HIV-1 infection. Treatment-experienced patients with HIV-1 infection also experienced beneficial virological effects when treated with similar regimens. Emtricitabine/tenofovir DF in combination with various boosted PIs was generally well tolerated by adults with HIV-1 infection.Drugs 02/2009; 69(7):843-57. DOI:10.2165/00003495-200969070-00005 · 4.13 Impact Factor
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ABSTRACT: Our goal was to determine the incidence rate and risk factors for loss to follow-up (LTFU) of HIV-infected patients in Northern France. We estimated the incidence rate of LTFU in 1,007 HIV-infected patients under care from January 1997 to December 2006. We then investigated potential risk factors for LTFU at inclusion and during follow-up. The incidence of LTFU was estimated to be 3.5 per 100 person-years. Risk factors for LTFU at enrolment in a multivariate Cox model were age <30 years (hazard ratio [HR] 1.66 versus >40 years, 95% confidence interval [CI] 1.04-2.64), transmission by injection drug use (HR 5.26 versus men who have sex with men, 95% CI 2.90-9.52), no phone number provided (HR 5.4, 95% CI 3.6-8.2), no primary care physician (HR 2.10, 95% CI 1.25-3.52) and sub-Saharan African origin (HR 2.09, 95% CI 1.36-3.22). Patients with CD4(+) T-cell counts <200 cells/mm(3) (HR 0.49 versus >/=350 cells/mm(3), 95% CI 0.32-0.76) and 200-349 cells/mm(3) at baseline (HR 0.63 versus >/=350 cells/mm(3), 95% CI 0.41-0.98) had a decreased risk of LTFU. During follow-up, the risk of LTFU increased when the most recent CD4(+) T-cell count was <200 cells/mm(3) (HR 2.06, 95% CI 1.16-3.66), the patient was not on highly active antiretroviral therapy (HAART; HR 4.20, 95% CI 2.66-6.61) and the patient was on HAART but had a detectable viral load (HR 1.92, 95% CI 1.19-3.01). Our findings will help clinicians recognize patients who require additional support for retention in care, including younger patients, injection drug users, people of sub-Saharan African origin, patients who are healthier at enrolment and patients who do not adhere to HAART during follow-up.Antiviral therapy 02/2009; 14(4):567-75. · 3.14 Impact Factor
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ABSTRACT: Study 934 was an open-label, randomized Phase III study of emtricitabine + tenofovir DF + efavirenz (FTC + TDF + EFV) compared with lamivudine + zidovudine + efavirenz (3TC + ZDV + EFV) in antiretroviral therapy-naïve HIV-1 infected subjects. Baseline genotyping revealed the presence of primary nonnucleoside reverse transcriptase inhibitor resistance (NNRTI-R) in 22 of 509 enrolled patients (4.3%, 11 subjects in each group). The 487 subjects without baseline NNRTI-R formed the primary efficacy population (modified intent-to-treat population). Through 144 weeks, 50 of 487 modified intent-to-treat subjects (FTC + TDF + EFV, n = 19; 3TC + ZDV + EFV, n = 31) were analyzed for resistance development after virologic failure. NNRTI-R, primarily the K103N mutation, was the most common form of resistance that developed in both groups. No subject on FTC + TDF + EFV developed the K65R mutation. Significantly fewer subjects on FTC + TDF + EFV compared with 3TC + ZDV + EFV developed the M184V/I mutation (two versus 10, respectively, P = 0.021). Thymidine analog mutations developed in two subjects on 3TC + ZDV + EFV. Subjects with baseline NRTI genotypic resistance (TAMs, n = 13) or non-B HIV-1 subtypes (n = 28) showed no evidence of reduced treatment responses in either group. Nine of 22 patients with baseline NNRTI-R experienced virologic failure (FTC + TDF + EFV, n = 4; 3TC + ZDV + EFV, n = 5); seven of nine developed M184V/I and/or additional NNRTI-R, but none developed K65R. Baseline NNRTI-R was significantly associated with virologic failure in both groups (P < 0.001).JAIDS Journal of Acquired Immune Deficiency Syndromes 07/2009; 52(2):209-21. DOI:10.1097/QAI.0b013e3181b05f7c · 4.39 Impact Factor