A phase II clinical study of the long-term safety and antiviral activity of enfuvirtide-based antiretroviral therapy.
Lalezari, Jacob P a; Eron, Joseph J b; Carlson, Margrit c; Cohen, Calvin d; DeJesus, Edwin e; Arduino, Roberto C f; Gallant, Joel E g; Volberding, Paul h; Murphy, Robert L i; Valentine, Fred j; Nelson, Emily L k; Sista, Prakash R k; Dusek, Alex k; Kilby, J Michael l
17(5):691-698, March 28, 2003.
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Objectives: The primary objective was to determine the long-term safety of the subcutaneous self-administration of enfuvirtide. Secondary objectives included the determination of enfuvirtide pharmacokinetics and antiviral activity and the immunological response to the enfuvirtide-containing regimen.
Methods: A multicenter 48-week uncontrolled open-label rollover study was conducted on 71 HIV-infected adults recruited from previous enfuvirtide clinical trials. Patients with extensive previous use of protease and reverse transcriptase inhibitors received a twice-daily dose of 50 mg enfuvirtide subcutaneously (45 mg deliverable) combined with two or more antiretroviral drugs selected for each individual, guided by resistance testing and previous treatment history.
Results: The mean baseline plasma HIV-RNA level was 4.81 log10 copies/ml and the mean CD4 cell count was 134.8 cells/[mu]l. The majority (86.9%) of treatment-emergent adverse events were grade 2 or less in severity. Injection site reactions were common, but no patients discontinued treatment. A mean HIV-RNA change of -1.33 log10 was achieved within 14 days of treatment initiation. At week 48, approximately one-third of all patients in the intent-to-treat population maintained significant suppression of plasma HIV RNA, with either less than 400 copies/ml or more than a 1.0 log10 decline from baseline. The mean gain in absolute CD4 cell counts at 48 weeks was 84.9 cells/[mu]l. Trough plasma concentrations of enfuvirtide were consistently higher than target concentrations.
Conclusion: Self-administration of enfuvirtide is not associated with unexpected toxicities for up to one year, and combined with oral antiretroviral drugs was associated with a significant decrease in HIV RNA and an increase in CD4 cell counts.
(C) 2003 Lippincott Williams & Wilkins, Inc.