Journal Article

Plasma Concentrations of Efavirenz and Nevirapine among HIV-Infected Patients with Immunological Failure Attending a Tertiary Hospital in North-Western Tanzania

Mshana, Stephen E., Kidola, Jeremiah, Klinker, Hartwig, Gunda, Daniel W., Kidenya, Benson R., Kasang, Christa, Kalluvya, Samuel E., Kongola, Gilbert W., Kabangila, Rodrick

2013

Overview

Sub-therapeutic and supra-therapeutic plasma concentrations of antriretrovirals are the significant causes of treatment failure and toxicity respectively among HIV-infected patients. We conducted this study to determine the pattern of efavirenz and nevirapine plasma drug concentrations among adult HIV-infected patients with immunological failure attending at a tertiary hospital in North-western Tanzania. A cross-sectional study was conducted among adult HIV-infected patients with immunological failure who have been on either efavirenz or nevirapine based antiretroviral regimen for more than 6 months. Patients were serially enrolled through routine Care and Treatment Clinic (CTC) activities. Plasma drug concentrations for efavirenz and nevirapine were determined by high performance liquid chromatography (HPLC) and Gas Chromatography (GC) respectively. Demographic, clinical and laboratory data such as viral load and CD4 counts were collected. Data analysis was done using STATA 12. Of the 152 patients with immunological failure enrolled, the sub-therapeutic, therapeutic and supra-therapeutic plasma antiretroviral drug concentrations were found in 43/152 (28.3%), 76/152 (50.0%) and 33/152 (21.7%) respectively. Half of the patients were outside therapeutic window with either sub-therapeutic or supra-therapeutic plasma ARV drug concentrations. There was a significant difference in distribution of ARV adherence (p-value<0.001), NRTI backbone (p-value = 0.039), HIV stage (p-value = 0.026) and viral load (p-value = 0.007) within sub-therapeutic, therapeutic and supra-therapeutic ARV plasma drug concentrations. There is a wide inter-individual variability of plasma ARV concentrations among HIV patients with immunological failure, with a large proportion of patients being outside therapeutic window. This variability is significant based on ARV adherence, NRTI backbone, viral load and HIV stage. Routine therapeutic drug monitoring (TDM) could assist identifying these patients early and making timely correction to avoid virological failure, poor immunological outcome and prevent associated drug toxicities. Nonetheless, ARV adherence should be strictly emphasized on HIV patients with immunological failure.

• Publisher: Public Library of Science,Public Library of Science (PLoS)
• Subject: Acquired immune deficiency syndrome / Adhesion / Adult / AIDS / Analysis / Antiretroviral agents / Antiretroviral drugs / Backbone / Benzoxazines - administration & dosage / Benzoxazines - pharmacokinetics / Care and treatment / CD4 antigen / Data analysis / Data processing / Demographics / Drug dosages / Drug Monitoring / Drug resistance / Drug therapy / Efavirenz / Failure / Female / Gas chromatography / Health aspects / High performance liquid chromatography / Highly active antiretroviral therapy / HIV / HIV infections / HIV Infections - blood / HIV Infections - drug therapy / HIV Infections - epidemiology / HIV patients / HIV-1 / Hospitals / Human immunodeficiency virus / Humans / Immunology / Infections / Information management / Internal medicine / Liquid chromatography / Male / Medical research / Medicine / Middle Aged / Nevirapine / Nevirapine - administration & dosage / Nevirapine - pharmacokinetics / Patients / Pharmacy / Reverse Transcriptase Inhibitors - administration & dosage / Reverse Transcriptase Inhibitors - pharmacokinetics / Tanzania - epidemiology / Therapeutic drug monitoring / Toxicity / Variability / Viral Load - drug effects