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JAMES D. SCOTT, PHARM. D., is Assistant Professor of Pharmacy Practice, Western University of Health Sciences, 309 East 2nd Street, Pomona, CA 91766 (jdscott{at}westernu.edu).

Purpose. The rationale, advantages, and disadvantages of attempting to enhance the efficacy of a primary protease inhibitor (PI) with ritonavir in the management of HIV infection, especially in patients who have previously undergone highly active antiretroviral therapy (HAART), are discussed. Summary. PIs are pivotal components of the HAART regimens used to fight HIV infection. Long-term viral suppression remains a major clinical challenge. Certain pharmacologic features of many PIs, such as their limited oral bioavailability, necessitate burdensome dosage schedules, creating a barrier to patient adherence. Compliance may be further compromised by adverse events. Any factors that undermine adherence may increase the risk that plasma drug concentrations will be suboptimal and that viral resistance and subsequent treatment failure will develop. The pharmacokinetic enhancement, or "boosting," of PI levels with low-dose ritonavir may increase PI potency and efficacy, as well as decrease the emergence of viral resistance, reduce the pill burden, and simplify administration. A number of clinical studies suggest that PI-boosted regimens are safe and effective in HIV-infected patients who have been previously treated with antiretroviral agents, but more research is needed. Conclusion. PI boosting with ritonavir can improve PI pharmacokinetics so that potency and efficacy are increased and regimens are simplified, thereby potentially reducing antiretroviral resistance and promoting patient adherence. Index terms: Antiretroviral agents; Blood levels; Combined therapy; Compliance; Dosage schedules; Drugs, availability; HIV infections; Patients; Pharmacokinetics; Resistance; Ritonavir; Toxicity

 

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