Toward genetic rationalization of antiretroviral therapy for HIV.

Daar et al. have extended the observations of Barbour et al. on the correlation between disease progression and standardized HIV polymerase activity in vitro. Polymerase thus joins accessory genes (nef rev tat vif vpr vpu reviewed in) as well as tropism-determining envelope as a potentially useful prognostic marker for disease progression and treatment initiation albeit one that must be functionally assayed (like envelope tropism) rather than genetically screened. For treatment-experienced patients reverse transcriptase and protease are already widely monitored for mutations predictive of drug resistance (reviewed). Thus Daar et al. provide one more step toward the individualization of antiretroviral therapy (ART) by fine tuning decisions made in the context of CD4 cell counts viremia and drug resistance. (excerpt)