Determinants of nevirapine plasma levels and clinical outcomes in HIV patients at Kenyatta National Hospital, Kenya.

Background Nevirapine is a non-nucleoside reverse transcriptase inhibitor used as an antiretroviral agent for the treatment of HIV/AIDS. Current dosing schedules are based on pharmacokinetic studies in Caucasian populations and thus there may be high incidences of toxicity or sub-optimal nevirapine plasma levels that might limit its use and therapeutic success in non-Caucasians. Objective This study determined variability of steady-state nevirapine plasma levels and the influence of factors such as genetic polymorphisms, adherence and co-administered antiretroviral drugs in HIV positive patients at the Comprehensive Care Centre (CCC) at Kenyatta National Hospital (KNH). This study also evaluated the influence of nevirapine plasma levels on clinical outcomes such as maximum CD4 cell counts attainable during treatment. Methods A high performance liquid chromatography (HPLC) method utilizing ultraviolet (UV) detection was optimized and validated for determination of nevirapine in plasma. A descriptive one arm cross sectional study was conducted nested in a larger study on 241 HIV patients on nevirapine based antiretroviral therapy (ART) who attended the KNH CCC in 2014. Historical blood samples collected from the patients on ART for at least six months were analyzed using the HPLC-UV method to determine the steady-state nevirapine plasma levels. Previously collected data on baseline sociodemographic characteristics, clinical data for at least six months ART treatment and CYP2B6 genotypes was collated with the nevirapine levels. Descriptive, inferential, and linear regression analysis was performed to determine predictors of nevirapine plasma levels and clinical outcomes. Results The HPLC-UV method was selective and sensitive with a limit of quantification of 0.5 μg/mL. The accuracy of the method was 2.3% with inter- and intra-day precision of 7.2% and 4.7% respectively. The analytical range of the method was wide from 0.5 to 25 μg/mL with a recovery of 91.8%. xvii Steady-state nevirapine plasma levels varied widely ...