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Clinicians seldom deviate from the standard 600-mg daily dose of efavirenz in adults, even though we know that drug levels vary significantly from person to person and that elevated levels may correlate with serious side effects. How much do individual genetic variants contribute to this uncertainty?
Researchers with the ongoing WIHS study studied nine possibly relevant genes among 111 HIV-infected women who were receiving efavirenz-based antiretroviral therapy. In an intensive 24-hour pharmacokinetic study, participants' mean efavirenz area-under-the-concentration-time curve (AUC) in plasma ranged from 11 to 519 µg × hours/mL. A multivariate analysis showed that three specific genetic variants predicted higher AUCs, as did two clinical mark…