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INFECTIOUS DISEASES

Pharmacologic Perspectives for Once-Daily Antiretroviral Therapy

Assistant Professor, Department of Clinical Pharmacy, School of Pharmacy, University of Colorado Health Sciences Center, Box C238, 4200 E. Ninth Ave., Denver, CO 80262-0238, fax 303/315-1721, Peter.Anderson{at}uchsc.edu

Reprints: Peter L Anderson PharmD

OBJECTIVE: To contrast available once-daily antiretroviral agents and combinations of these agents from a clinical pharmacologic viewpoint.

DATA SOURCES: Data were extracted from publications and major HIV conference proceedings cited in MEDLINE (1966–March 2004) using the search terms antiretroviral therapy, combination therapy, once-daily therapy, and pharmacokinetics. Additional references were obtained from the bibliographies of these sources.

STUDY SELECTION AND DATA EXTRACTION: Information pertaining to pharmacologic perspectives for once-daily antiretroviral agents was selected.

DATA SYNTHESIS: Maximal and durable suppression of plasma HIV RNA, the principal goal of therapy, depends on the intrinsic antiviral activity of the antiretroviral regimen. A favorable tolerability/toxicity profile is also fundamentally important. All once-daily agents exhibit some pharmacologic limitations or lack adequate long-term follow-up. Of available agents, efavirenz has a long and distinguished efficacy record, with reasonable safety and moderate tolerability. Lamivudine, and newer agents such as atazanavir (or atazanavir/ritonavir), emtricitabine, fosamprenavir/ritonavir, and tenofovir, may offer pharmacologic advantages in the current state of once-daily therapy. Important considerations exist for coadministering once-daily agents including drug–drug interactions, drug–food incompatibilities, and synergistic toxicities. Few controlled studies have compared once-daily regimens with conventional regimens.

CONCLUSIONS: Progress has been made toward once-daily therapy, but more clinical experience with available agents is needed, including comparative studies of entirely once-daily regimens versus conventional regimens. Limitations of currently available agents signify a need for improved antiretroviral utilization or new alternative agents.

Key Words: antiretroviral therapy, combination therapy, once-daily therapy, pharmacokinetics

Published Online, October 12, 2004. www.theannals.com, DOI 10.1345/aph.1E036

THIS ARTICLE IS APPROVED FOR CONTINUING EDUCATION CREDIT
ACPE UNIVERSAL PROGRAM NUMBER: 407-000-04-035-H02