S24   Optimizing Available Antiretroviral Therapies

Diane Havlir
Univ. of California, San Diego

Advances in our understanding of viral dynamics, host immunity, pharmacokinetics, drug resistance, potency, and adherence provide the opportunity to more effectively use available antiretroviral agents. These advances and the uncertainties of long-term toxicities have called into question a number of assumptions about antiretroviral therapy, including when to start, interrupt, switch, and stop therapy.

Using therapy most effectively depends on initiating it at a time that optimizes its known benefits. Issues of drug tolerance have moved to the forefront for treatment-naive patients as multiple drug regimens now have sufficient potency to assure long-term viral suppression.

Decisions of when and how to switch therapy for virologic rebound depend on adherence, drug cross resistance, current and future treatment options, and the effect of “partial” viral suppression. Temporary interruptions of therapy represent an exciting research approach that may be useful in stimulating the host immune system during acute HIV infection. They may also enhance treatment responses in patients with multiple drug-resistant HIV. Combining available protease inhibitors with low-dose ritonavir represents a major advance and accomplishes therapeutic goals of optimizing drug exposure, simplifying dosing, and improving adherence.

Drug resistance testing is critical at all stages of HIV disease. In areas with documented drug resistance in newly infected patients, resistance testing is critical to the design of initial therapy. In the setting of virologic failure, resistance testing allows refining of regimens in initial therapy and designing of efficient, effective, and potentially less toxic regimens in patients with high-level resistance. Optimizing available agents will depend on incorporating more active pharmacologic monitoring into patient management.