Pharmacologic Perspectives for Once-Daily Antiretroviral Therapy

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Abstract
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.

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