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

Background: 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. Materials and Methods: 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. Results: 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 supratherapeutic ARV plasma drug concentrations. Conclusion: 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

Modeling solutions to Tanzania's physician workforce challenge

Background: There is a great need for physicians in Tanzania. In 2012, there were approximately 0.31 physicians per 10,000 individuals nationwide, with a lower ratio in the rural areas, where the majority of the population resides. In response, universities across Tanzania have greatly increased the enrollment of medical students. Yet evidence suggests high attrition of medical graduates to other professions and emigration from rural areas where they are most needed. Objective: To estimate the future number of physicians practicing in Tanzania and the potential impact of interventions to improve retention, we built a model that tracks medical students from enrollment through clinical practice, from 1990 to 2025. Design: We designed a Markov process with 92 potential states capturing the movement of 25,000 medical students and physicians from medical training through employment. Work possibilities included clinical practice (divided into rural or urban, public or private), non-clinical work, and emigration. We populated and calibrated the model using a national 2005/2006 physician mapping survey, as well as graduation records, graduate tracking surveys, and other available data. Results: The model projects massive losses to clinical practice between 2016 and 2025, especially in rural areas. Approximately 56% of all medical school students enrolled between 2011 and 2020 will not be practicing medicine in Tanzania in 2025. Even with these losses, the model forecasts an increase in the physician-to-population ratio to 1.4 per 10,000 by 2025. Increasing the absorption of recent graduates into the public sector and/or developing a rural training track would ameliorate physician attrition in the most underserved areas. Conclusions: Tanzania is making significant investments in the training of physicians. Without linking these doctors to employment and ensuring their retention, the majority of this investment in medical education will be jeopardized