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 19 90-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 d ifferences among patients. Patients receiving the same dose of an antiretro viral agent will not have the same systemic or intracellular concentration because of interpatient variability in drug absorption, distribution, metab olism, and excretion. Pharmacologic theory and available clinical data supp ort relationships between drug concentration and anti-HIV effect. Thus, var iability in drug concentrations contributes to variability in antiviral eff ect. Desirable pharmacologic characteristics for an antiretroviral drug inc lude high oral bioavailability, a long elimination half-life, low intra- an d interpatient pharmacokinetic variability, and a predictable dose-concentr ation-effect relationship. CONCLUSIONS: Treatment of the individual who is infected with HIV is a chal lenging long-term undertaking. Optimal management requires synthesis of a r apidly evolving base of basic and clinical knowledge. The selection of an a ntiretroviral regimen based on an understanding of the degree to which each individual agent possesses the desired pharmacologic characteristics shoul d help the healthcare provider to translate the therapeutic principles of t reatment of HIV infection into clinical reality for all patients.