Adherence to ARV and its association with immune status among HIV infected children aged 2-14 years in Dar es salaam

Abstract

Background Adherence is particularly critical with antiretroviral drugs in treatment of paediatric HIV infection where adherence of more than 95% is necessary to maximize the benefit of antiretroviral drugs. Studies on adherence in developed world have demonstrated that higher level of drugs adherence is associated with improved virological, immunological and clinical outcome. Despite the benefit of antiretroviral drugs in paediatric HIV infection, there are consequences to non adherence including disease progression, failure of viral suppression, decrease in CD4 cell count, drug resistance, risk of transmission of resistant virus and limited treatment options. It is therefore important to identify children with non adherence in order to intervene before developing drug resistance and treatment failure. Objective The aim of this study was to determine proportion of good adherence to ARV measured by caretaker report, medication return, plasma nevirapine concentration and its association with immune status among HIV-infected children in Dar es Salaam. Methodology A cross-sectional study was conducted between May and October 2011 in three Municipal hospitals (Mwananyamala, Temeke and Amana) in Dar es Salaam region. A total of 300 children aged 2-14 years on nevirapine based ARV regimen for at least six month were enrolled consecutively as they attend CTC. The study involved assessment of nutritional status and adherence to ARV. A single blood sample for CD4 count/percent and nevirapine plasma concentration was taken on the day of assessment. CD4 count was determined using flow cytometry and nevirapine plasma concentration was determined using reversed phase High Performance Liquid Chromatography (HPLC/UV). Proportions were used to summarise categorical variables and Chi square test as well as Fisher’s exact test were used to test for statistical difference between thesevariables. Mean and standard deviation was used to summarise continuous variables. A logistic regression model was used to assess the independent predictors of the outcome. Results A total of 300 children met inclusion criteria, the mean age (SD) of these children was 8(3) years and 50.7% were female. Caretaker report and medication return showed good adherence (98% and 97%) respectively. However adherence assessed by nevirapine plasma concentration was 85%significantly lower than that of caretaker report and medication return (p<0.001). Furthermore, the agreement between nevirapine plasma concentration and medication return and between nevirapine plasma concentration and self report were weak (k=0.131) (k=0.09) respectively. This means that care taker report and medication return reflected good adherence to ARV’s which was contrary to what was found when using nevirapine plasma concentrations. Nevirapine plasma concentration below 3μg/ml was associated with immunosuppression (p=0.021) while medication return >5% of prescribed dose and caretaker reported missed dose were not associated with immunosuppression (p=0.474), (p=0.569) respectively. Therefore, nevirapine plasma concentration could be a predictor of adherence and correlate with immunosuppression when compared to medication return and caretaker report. Other independent factors associated with immune status were infections (OR=2.02, CI=1.01- 3.41), Age of the child (OR=6.00, CI=2.96-12.17) and duration of ARV use (OR=6.79, CI=2.69-17.2). Conclusions. Nevirapine plasma concentration is a good predictor of adherence and correlate well with immunosuppression. Caretaker report and medication return were poor predictors of adherence. Non adherence by nevirapine plasma concentration was high (15%) suggesting that in every 10 children on ARV 2 did not adhere to medication. This is alarming considering the management of HIV and AIDS in paediatric patients.