The relationship between zidovudine, lamivudine and nevirapine plasma drug levels and antiretroviral treatment outcomes in Nigeria children living with HIV

Abstract

Plasma concentrations of antiretrovirals are significant and important determinants of treatment failure and toxicity. The relationship between antiretroviral pharmacokinetic exposures and immunovirological outcomes has not been extensively studied in our setting. The aim of this study was to investigate the relationship between antiretroviral plasma concentrations and virological and immunological treatment outcomes in children living with human immunodeficiency virus (HIV) A retrospective collection of demographic, clinical , laboratory data and a prospective determination of plasma drug concentrations in 120 children aged 2-14 years after two years of receiving fixed dose zidovudine, lamivudine and nevirapine tablets using a simple, rapid, sensitive and validated method of high performance liquid chromatography with UV detection for simultaneous quantification of zidovudine, lamivudine and nevirapine in human plasma. All analyses were performed using graph pad prism version 5.0. A perfect agreement (p<.001) was found between nevirapine drug levels and prescriptionrefill visit adherence records (Kappa 0.093). Plasma zidovudine, lamivudine and nevirapine concentrations were not statistically associated with virological success (Viral load <400copies/μl ) and immunological success (CD4 cells >100 cells/mm3). At 2 years zidovudine, lamivudine and nevirapine therapeutic levels, zidovudine supra therapeutic levels ,and nevirapine subtherapeutic levels were respectively significantly associated with immunologic success (CD4%>15 %). Low nevirapine levels can be used to identify those that require adherence counseling. Despite good virological and immunological outcomes, plasma concentrations of zidovudine, lamivudine and nevirapine were not significantly associated with virological and immunological outcomes (Absolute CD4 counts) but was significantly associated with immunological outcomes (CD4%). Plasma drug levels may be good surrogates of adherence but not of treatment outcomes. Monitoring CD4% remains important to optimize paediatric HIV treatment.

Keywords: Antiretroviral treatment, children, therapeutic drug monitoring, treatment outcomes, immune-virological outcomes, plasma concentrations, zidovudine, lamivudine and nevirapine