Abstract
Background:Patients’ clinical outcomes and pharmacogenetic factors are important predictors of nevirapine (NVP) plasma concentration. This study evaluated the association of socio-demographic factors and Cytochrome P450 2B6 (CYP2B6) polymorphisms with NVP plasma concentrations among patients receiving antiretroviral therapy (ART) treatment in western and coastal Kenya.Methods:Blood samples were collected from 377 consenting HIV adult patients receiving an NVP-based first-line ART regimen. A detailed sociodemographic questionnaire was administered. NVP plasma concentration was measured by liquid chromatography - tandem mass spectrometry (LC-MS/MS). CYP2B6 c.516 G>T rs3745274 and c.983T>C genotypes were evaluated using real-time polymerase chain reaction. HIV drug resistance mutations were detected using an in-house genotypic assay.Results:The patients’ mean age was 41.6 (SD ± 11.5) years and the majority (59.2%) were female. The mean duration of ART was 5.1 (SD ± 4.8) years. Overall NVP plasma levels ranged from 4-44207 ng/mL (median 6213 ng/mL, IQR 3097–8606.5 ng/mL). There were 105 (25.5%) participants with NVP levels of <3100 ng/mL, associated with poor viral suppression. Multivariate linear regression analysis showed CYP2B6 516 G>T polymorphism (β 0.71, 95% CI 0.4–0.98; p<0.0001), male gender (β 0.45, 95% CI 0.01–0.9; p=0.047) and presence of HIV drug-resistant virus (β 1.98, 95% CI 1.24–2.72; p<0.001) were the independent factors influencing NVP plasma concentration.Conclusions:The majority of patients receiving an NVP-based ART regimen had plasma concentrations within the therapeutic range. CYP2B6 516 G>T polymorphism, gender and presence of a HIV drug-resistant mutation significantly influences NVP plasma concentration. Routine pharmacogenetic testing and measurement of NVP plasma concentrations, considering gender and presence of HIV drug-resistant mutations are key to ensuring optimal ART treatment outcomes in Kenya.
Highlights
Patients’ clinical outcomes and pharmacogenetic factors are important predictors of nevirapine (NVP) plasma concentration
Kenya is among the countries that have adopted the 2015 World Health Organization (WHO) recommendations, which require immediate initiation of antiretroviral therapy (ART) to people diagnosed with HIV, aimed at increasing ART access further[2]
At the time of the study, the first-line ART guidelines for children, youth and adults in Kenya typically contained a backbone of two nucleoside reverse transcriptase inhibitors (NRTIs; zidovudine [AZT], stavudine [d4T], tenofovir [TDF] or lamivudine [3TC]), plus one non-nucleoside reverse transcriptase inhibitor (NNRTI): either nevirapine (NVP) or efavirenz (EFV)[2]
Summary
Any reports and responses or comments on the article can be found at the end of the article. Keywords Nevirapine plasma concentration, pharmacogenetics and clinical parameters, HIV-1 patients in Kenya
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