High exposure to nevirapine in plasma is associated with an improved virological response in HIV-1-infected individuals

Objective: To explore relationships between exposure to nevirapine and the virological response in HIV-l-infected individuals participating in the INC AS trial. Methods: The elimination rate constant of plasma HIV-1 RNA (k) was calculat ed during the first 2 weeks of treatment with nevirapine, zidovudine and di danosine in 51 anti retroviral-naive HIV-l-infected patients. The relations hips between the value of k, the time to reach an undetectable HIV-1 RNA co ncentration in plasma (< 20 copies/ml) and the success of therapy after 52 weeks of treatment as dependent variables and the exposure to nevirapine, b aseline HIV-1 RNA and baseline CD4 cell count as independent variables, wer e explored using linear regression analyses, proportional hazard models and logistic analyses, respectively. Results: The value of k for HIV-1 RNA in plasma was positively and signific antly associated with the mean plasma nevirapine concentration during the f irst 2 weeks of therapy (P = 0.011) and the baseline HIV-1 RNA (P = 0.008). Patients with a higher exposure to nevirapine reached undetectable levels of HIV-1 RNA in plasma more rapidly (P = 0.03). From 12 weeks on, the media n nevirapine plasma concentration was significantly correlated with success of therapy after 52 weeks (P < 0.02). Conclusions: A high exposure to nevirapine tin a twice daily regimen) is si gnificantly associated with improved virological response in the short as w ell as in the long term. These findings suggest that optimization of nevira pine concentration might be used as a toot to improve virological outcome i n (antiretroviral-naive) patients treated with Introduction nevirapine. (C) 2001 Lippincott Williams & Wilkins.