The variations in plasma efavirenz pharmacokinetics have been associated with clinical outcomes. Minimum plasma concentrations define therapeutic success, while maximum concentrations define the threshold for adverse drug reactions [17,18]. High intrapatient CP 673451 variability in efavirenz plasma trough concentration, as measured using the integrated pharmacokinetic

adherence measure (IPAM) score, was associated with higher risk of viral rebound [2], while Pfister et al. demonstrated that a 100% increase in clearance above the population mean was associated with clinical failure among highly active antiretroviral therapy (HAART)-naïve patients [10]. In the light of reports that efavirenz-based regimens are superior to other regimens in terms of efficacy, cost-effectiveness and dosing convenience [19], efavirenz is currently used in first-line regimens in most resource-limited settings, and so a better understanding of the pharmacokinetics of efavirenz and the clinical outcomes of efavirenz treatment in African populations is needed. The aim of this study was to obtain a detailed understanding of the pharmacokinetics of the nonnucleoside reverse transcriptase inhibitor efavirenz in HIV-infected, antiretroviral therapy (ART)-naïve Ugandans during the initial treatment period. Consenting HIV-seropositive Ugandan patients initiating

efavirenz-based HAART regimens at Bwera Hospital in south-western Galunisertib manufacturer Uganda between September 2007 and March 2009 were screened for participation in the study. All participants were screened for tuberculosis, alcoholism, pregnancy, psychiatric illnesses, previous antiretroviral experience and risk of nonadherence to therapy and schedule. At the time, the centre used the Centers for Disease Control and Prevention (CDC)/World Health Organization (WHO) classification to decide whether or not

to initiate patients on ART. CD4 testing was therefore Thiamine-diphosphate kinase offered to all patients selected to start ART, and this was also considered a screening procedure, as patients whose CD4 cell counts were found to be above the national cut-off were not started on treatment. All patients reported that they took 960 mg of cotrimoxazole daily for Pneumocystis carinii pneumonia (PCP) chemoprophylaxis prior to and during the study period. All enrolled participants were administered a standardized diet with a limited fat content, and were admitted overnight on the 1st and 14th days of treatment for clinical evaluation, observed dosing and blood collection. They were all initiated on a first-line regimen according to the national policy; this regimen consisted of 150 mg lamivudine/300 mg zidovudine (Combivir®; Hetero House, Hyderabad, Andhra Pradesh, India) taken twice a day, and 600 mg efavirenz (Stocrin®; Merck, Sharpe & Dohme, Whitehouse Station, NJ, USA) taken once every evening (17:00–20:00 h).