Abstract
BackgroundChildren are subject to varying drug pharmacokinetics which influence plasma drug levels, and hence treatment outcomes especially for drugs like efavirenz whose plasma concentrations are directly related to treatment outcomes. This study is aimed at determining plasma efavirenz concentrations among Tanzanian pediatric HIV-1 patients on efavirenz-based combination antiretroviral therapy (cART) and relating it to clinical, immunological and virologic treatment responses.MethodsA cross sectional study involving pediatric HIV patients aged 5–15 years on efavirenz-based cART for ≥ 6 months were recruited in Dar es Salaam. Data on demographics, cART regimens, efavirenz dose and time of the last dose were collected using structured questionnaires and checklists. Venous blood samples were drawn at 10–19 h post-dosing for efavirenz plasma analysis.ResultsA total of 145 children with a mean ± SD age of 10.83 ± 2.75 years, on cART for a mean ± SD of 3.7 ± 2.56 years were recruited. Median [IQR] efavirenz concentration was 2.56 [IQR = 1.5–4.6] μg/mL with wide inter-patient variability (CV 111%). Poor virologic response was observed in 70.8%, 20.8% and 15.9% of patients with efavirenz levels < 1 μg/mL, 1–4 μg/mL and > 4 μg/mL respectively. Patients with efavirenz levels of < 1 μg/mL were 11 times more likely to have detectable viral loads. Immunologically, 31.8% of children who had low levels (< 1 μg/mL) of efavirenz had a CD4 count of < 350 cells/μL.ConclusionWide inter-individual variability in efavirenz plasma concentrations is seen among Tanzanian children in routine clinical practice with many being outside the recommended therapeutic range. Virologic failure is very high in children with sub-therapeutic levels. Concentrations outside the therapeutic window suggest the need for dose adjustment on the basis of therapeutic drug monitoring to optimize treatment.
Highlights
Children are subject to varying drug pharmacokinetics which influence plasma drug levels, and treatment outcomes especially for drugs like efavirenz whose plasma concentrations are directly related to treatment outcomes
Treatment for Human immunodeficiency virus (HIV)-1 infections in Tanzania involves the use of a combination of antiretroviral drugs commonly with two Nucleoside Reverse Transcriptase Inhibitors (NRTI) and one Non-Nucleoside Reverse Transcriptase Inhibitor (NNRTI) [3]
The National Acquired Immunodeficiency Syndrome (AIDS) Control Program (NACP) guidelines currently recommend protease inhibitor (PI)-based regimens for all pediatric HIV patients previously exposed to nevirapine during prevention of mother to child transmission
Summary
Children are subject to varying drug pharmacokinetics which influence plasma drug levels, and treatment outcomes especially for drugs like efavirenz whose plasma concentrations are directly related to treatment outcomes. This study is aimed at determining plasma efavirenz concentrations among Tanzanian pediatric HIV-1 patients on efavirenz-based combination antiretroviral therapy (cART) and relating it to clinical, immunological and virologic treatment responses. Management of pediatric HIV infection using cART has shown substantial clinical benefits and improved quality of life such as improvement in immunologic status, sustained virologic suppression and enhancement of survival. Such favorable responses are similar to those observed in adults, these benefits are observed when optimal plasma drug concentrations of cART drugs are attained and maintained [2]. After reaching three years of age the protease inhibitor is replaced by an NNRTI efavirenz
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