Pharmacologic considerations for therapeutic success with antiretroviral agents

OBJECTIVE: To explore pharmacologic elements that contribute to therapeutic success with agents used for the treatment of HIV infection. DATA SOURCES: primary articles were identified through MEDLINE: (January 1990-January 1999) and secondary sources. Conference abstracts were selected by review of published proceedings. STUDY SELECTION AND DATA EXTRACTION: The author evaluated all articles, and relevant information was selected for incorporation into this review. DATA SYNTHESIS: Heterogeneity in the response to antiretroviral therapy has been attributed to virologic, immunologic, behavioral, and pharmacologic differences among patients. Patients receiving the same dose of an antiretroviral agent will not have the same systemic or intracellular concentration because of interpatient variability in drug absorption, distribution, metabolism, and excretion. Pharmacologic theory and available clinical data support relationships between drug concentration and anti-HIV effect. Thus, variability in drug concentrations contributes to variability in antiviral effect. Desirable pharmacologic characteristics for an antiretroviral drug include high oral bioavailability, a long elimination half-life, low intra- and interpatient pharmacokinetic variability, and a predictable dose-concentration-effect relationship. CONCLUSIONS: Treatment of the individual who is infected with HIV is a challenging long-term undertaking. Optimal management requires synthesis of a rapidly evolving base of basic and clinical knowledge. The selection of an antiretroviral regimen based on an understanding of the degree to which each individual agent possesses the desired pharmacologic characteristics should help the healthcare provider to translate the therapeutic principles of treatment of HIV infection into clinical reality for all patients.