Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2008 Mar 28:5:5.
doi: 10.1186/1742-6405-5-5.

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

Kimberly Y Smith  1 , Winkler G Weinberg #  2 , Edwin DeJesus  3 , Margaret A Fischl  4 , Qiming Liao  5 , Lisa L Ross  5 , Gary E Pakes  5 , Keith A Pappa  5 , C Tracey Lancaster  5 ; ALERT (COL103952) Study Team
Affiliations

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

Kimberly Y Smith et al. AIDS Res Ther. .

Abstract

Background: 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 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.

Results: At 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.

Conclusion: The 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.

PubMed Disclaimer

Figures

Figure 1
Figure 1
Proportion of patients with HIV-1 RNA < 400 copies/mL and < 50 copies/mL (intent-to-treat: missing/discontinuation = failure analysis).
Figure 2
Figure 2
Mean CD4+ cell counts at all study visits.
Figure 3
Figure 3
Proportion of patients with change in MDRD-determined glomerular filtration rate from baseline to week 48.
Figure 4
Figure 4
Median lipid values over the course of the study, with lines within shaded areas showing NCEP cut-offs.
See this image and copyright information in PMC

References

    1. Wire MB, Shelton MJ, Studenberg S. Fosamprenavir. Clinical pharmacokinetics and drug interactions of the amprenavir prodrug. Clin Pharmacokinet. 2006;45:137–168. doi: 10.2165/00003088-200645020-00002. - DOI - PubMed
    1. Orrick JJ, Steinhart CR. Atazanavir. Ann Pharmacother. 2004;38:1664–1674. doi: 10.1345/aph.1D394. - DOI - PubMed
    1. Cooper CL, van Heeswijk RPG, Gallicano K, Cameron DW. A review of low-dose ritonavir in protease inhibitor combination therapy. Clin Infect Dis. 2003;36:1585–1592. doi: 10.1086/375233. - DOI - PubMed
    1. LEXIVA® (fosamprenavir calcium tablets) Product labeling. GlaxoSmithKline; 2007.
    1. Ruane PJ, Luber AD, Wire MB, Lou Y, Shelton MJ, Lancaster CT, Pappa KA, for the COL10053 Study Team Plasma amprenavir pharmacokinetics and tolerability following administration of 1,400 milligrams of fosamprenavir once daily in combination with either 100 or 200 milligrams of ritonavir in healthy volunteers. Antimicrob Agents Chemother. 2007;51:560–565. doi: 10.1128/AAC.00560-06. - DOI - PMC - PubMed