Adherence, resistance, and timing: current issues in the use of new therapies.

Nucleoside reverse transcriptase inhibitors (nucleoside analogues) are a central component of HAART regimens. Optimal adherence to and activity of the "nucleoside analogue backbone" is required to preserve the utility of the more cross-resistant protease inhibitor and nonnucleoside analogue components of a highly active regimen, and a systematic approach to nucleoside analogue sequencing is needed to preserve the clinical activity of this class. As HIV treatment strategies move toward the long-term management of a chronic infection, treatment issues such as convenience, safety, and tolerability become even more important. Acute and chronic safety issues associated with individual drug classes are a growing concern. Because adherence is linked to convenience and tolerability, new agents with favorable safety profiles, low pill burdens, and little or no selection for drug resistance will be required to ensure long-term viral suppression.