Fosamprenavir or atazanavir once daily boosted with ritonavir 100 mg, plus tenofovir/emtricitabine, for the initial treatment of HIV infection: 48-week results of ALERT.

C Tracey Lancaster,Alert (Col103952) Study Team ,Kimberly Y Smith,C Tracey Pakes,Margaret A Fischl,Edwin Dejesus,Lisa L Ross,Keith A Pappa,Qiming Liao,Winkler G Weinberg,Gary E Pakes

doi:10.1186/1742-6405-5-5

Abstract

BackgroundOnce-daily (QD) ritonavir 100 mg-boosted fosamprenavir 1400 mg (FPV/r100) or atazanavir 300 mg (ATV/r100), plus tenofovir/emtricitabine (TDF/FTC) 300 mg/200 mg, have not been compared as initial antiretroviral treatment. To address this data gap, we conducted an open-label, multicenter 48-week study (ALERT) in 106 antiretroviral-naïve, HIV-infected patients (median HIV-1 RNA 4.9 log10 copies/mL; CD4+ count 191 cells/mm3) randomly assigned to the FPV/r100 or ATV/r100 regimens.ResultsAt baseline, the FPV/r100 or ATV/r100 arms were well-matched for HIV-1 RNA (median, 4.9 log10 copies/mL [both]), CD4+ count (mean, 176 vs 205 cells/mm3). At week 48, intent-to-treat: missing/discontinuation = failure analysis showed similar responses to FPV/r100 and ATV/r100 (HIV-1 RNA < 50 copies/mL: 75% (40/53) vs 83% (44/53), p = 0.34 [Cochran-Mantel-Haenszel test]); mean CD4+ count change-from-baseline: +170 vs +183 cells/mm3, p = 0.398 [Wilcoxon rank sum test]). Fasting total/LDL/HDL-cholesterol changes-from-baseline were also similar, although week 48 median fasting triglycerides were higher with FPV/r100 (150 vs 131 mg/dL). FPV/r100-treated patients experienced fewer treatment-related grade 2–4 adverse events (15% vs 57%), with differences driven by ATV-related hyperbilirubinemia. Three patients discontinued TDF/FTC because their GFR decreased to <50 mL/min.ConclusionThe all-QD regimens of FPV/r100 and ATV/r100, plus TDF/FTC, provided similar virologic, CD4+ response, and fasting total/LDL/HDL-cholesterol changes through 48 weeks. Fewer FPV/r100-treated patients experienced treatment-related grade 2–4 adverse events.

Highlights

Once-daily (QD) ritonavir 100 mg-boosted fosamprenavir 1400 mg (FPV/r100) or atazanavir 300 mg (ATV/r100), plus tenofovir/emtricitabine (TDF/fumarate (TDF)/emtricitabine (FTC)) 300 mg/200 mg, have not been compared as initial antiretroviral treatment
Ritonavir 100 mg QD is the only boosting dose recommended for use with ATV 300 mg [7]
Patient selection Male and non-pregnant female outpatients were eligible for enrollment if they were t 18 years old, had HIV-1 infection documented by HIV-1 antibody enzyme-linked immunosorbent assay (ELISA) and Western blot test, were antiretroviral-naïve (

Summary

Introduction

Once-daily (QD) ritonavir 100 mg-boosted fosamprenavir 1400 mg (FPV/r100) or atazanavir 300 mg (ATV/r100), plus tenofovir/emtricitabine (TDF/FTC) 300 mg/200 mg, have not been compared as initial antiretroviral treatment. To address this data gap, we conducted an openlabel, multicenter 48-week study (ALERT) in 106 antiretroviral-naïve, HIV-infected patients (median HIV-1 RNA 4.9 log copies/mL; CD4+ count 191 cells/mm3) randomly assigned to the FPV/r100 or ATV/r100 regimens. Ritonavir 100 mg QD is the only boosting dose recommended for use with ATV 300 mg [7] This dose increases the ATV minimum plasma concentrations (Cmin) and area under the plasma concentration-time curve (AUC) 5-fold and 3-fold higher, respectively, than can be attained with unboosted ATV 400 mg QD [8]

Methods

Results

Discussion

Conclusion