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A phase II clinical study of the long-term safety and antiviral activity of enfuvirtide-based antiretroviral therapy

Lalezari, Jacob Pa; Eron, Joseph Jb; Carlson, Margritc; Cohen, Calvind; DeJesus, Edwine; Arduino, Roberto Cf; Gallant, Joel Eg; Volberding, Paulh; Murphy, Robert Li; Valentine, Fredj; Nelson, Emily Lk; Sista, Prakash Rk; Dusek, Alexk; Kilby, J Michaell

Clinical Science

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/μl. 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/μl. 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.

From the aQuest Clinical Research, San Francisco, CA, USA; bUniversity of North Carolina, Chapel Hill, Durham, NC, USA; cCenter for Clinical AIDS Research and Education, University of California, Los Angeles, CA, USA; dCommunity Research Initiative New England, Brookline, MA, USA; eIDC Research Initiative, Altamonte Springs, FL, USA; fUniversity of Texas Health Science Center, Houston, TX, USA; gDivision of Infectious Diseases, Johns Hopkins University School of Medicine, Baltimore, MD, USA; hUniversity of California and the San Francisco Veterans Affairs Medical Center, San Francisco, CA, USA; iDivision of Infectious Diseases, Northwestern University, Chicago, IL, USA; jAIDS Clinical Trials Unit and Center for AIDS Research, New York University School of Medicine, New York, NY, USA; kTrimeris Inc., Durham, NC, USA; and lUAB HIV Outpatient Clinic, University of Alabama, Birmingham, AL, USA.

Correspondence to: Jacob Lalezari, Quest Clinical Research, 2300 Sutter Street, Suite 202, San Francisco, CA 94115, USA. E-mail: drjay@questclinical.com

Received: 24 June 2002; revised: 7 November 2002; accepted: 12 November 2002.

© 2003 Lippincott Williams & Wilkins, Inc.