Influence of CYP2B6 and ABCB1 SNPs on nevirapine plasma concentrations in Burundese HIV-positive patients using dried sample spot devices

AIMS The pharmacokinetics (PK) and pharmacogenetics (PG) of nevirapine have been studied in rich and limited-resource countries. CYP2B6 single nucleotide polymorphisms (SNPs) have been associated with decreased drug clearance. We evaluated the PG determinants of nevirapine trough concentrations in a rural cohort in Burundi using easy to store and transport dried sample spot devices. METHODS A cross-sectional analysis in HIV-positive nevirapine-treated patients in Kiremba, north of Burundi, was performed in 2009. After blood withdrawal whole blood was stored on dried blood spots and plasma (after centrifugation) was placed on dried plasma spot devices and stored at room temperature. Nevirapine plasma and dried sample spot concentrations were compared to test the clinical usefulness of this method. SNPs in CYP2B6 and ABCB1 (using a real time PCR technique) were analyzed and associated with nevirapine plasma trough concentrations. RESULTS Nevirapine concentrations measured on dried plasma spot devices were highly related to plasma concentrations in 60 patients, although a negative bias was observed (-18%). Nevirapine trough concentrations were above the target concentration (3000 ng ml-1) in 84% of patients and they were associated with CYP2B6 SNPs (both at position 516 and 983). No effect of ABCB1 SNPs was noted. CONCLUSIONS Dried plasma spot devices are accurate tools for measuring nevirapine concentrations in rural settings where refrigeration is not available, despite a moderate underestimation bias. They allowed the evaluation of nevirapine concentrations in a cohort of HIV-infected people in rural Burundi, confirming very good exposure and correlation with PG polymorphisms in the CYP2B6 encoding gene.