Abstract
BackgroundOptimal adherence to antiretroviral therapy is critical to prevent HIV drug resistance (HIVDR) epidemic. The objective of the study was to investigate the best performing adherence assessment method for predicting virological failure in resource-limited settings (RLS).MethodThis study was a single-centre prospective cohort, enrolling 220 HIV-infected adult patients attending an HIV/AIDS Care and Treatment Centre in Dar es Salaam, Tanzania, in 2010. Pharmacy refill, self-report (via visual analog scale [VAS] and the Swiss HIV Cohort study-adherence questionnaire), pill count, and appointment keeping adherence measurements were taken.Univariate logistic regression (LR) was done to explore a cut-off that gives a better trade-off between sensitivity and specificity, and a higher area under the curve (AUC) based on receiver operating characteristic curve in predicting virological failure. Additionally, the adherence models were evaluated by fitting multivariate LR with stepwise functions, decision trees, and random forests models, assessing 10-fold multiple cross validation (MCV). Patient factors associated with virological failure were determined using LR.ResultsViral load measurements at baseline and one year after recruitment were available for 162 patients, of whom 55 (34%) had detectable viral load and 17 (10.5%) had immunological failure at one year after recruitment. The optimal cut-off points significantly predictive of virological failure were 95%, 80%, 95% and 90% for VAS, appointment keeping, pharmacy refill, and pill count adherence respectively. The AUC for these methods ranged from 0.52 to 0.61, with pharmacy refill giving the best performance at AUC 0.61.Multivariate logistic regression with boost stepwise MCV had higher AUC (0.64) compared to all univariate adherence models, except pharmacy refill adherence univariate model, which was comparable to the multivariate model (AUC = 0.64). Decision trees and random forests models were inferior to boost stepwise model.Pharmacy refill adherence (<95%) emerged as the best method for predicting virological failure. Other significant predictors in multivariate LR were having a baseline CD4 T lymphocytes count < 200 cells/μl, being unable to recall the diagnosis date, and a higher weight.ConclusionPharmacy refill has the potential to predict virological failure and to identify patients to be considered for viral load monitoring and HIVDR testing in RLS.Electronic supplementary materialThe online version of this article (doi:10.1186/1471-2458-14-1035) contains supplementary material, which is available to authorized users.
Highlights
Optimal adherence to antiretroviral therapy is critical to prevent Human immunodeficiency virus (HIV) drug resistance (HIVDR) epidemic
Viral load measurements at baseline and one year after recruitment were available for 162 patients, of whom 55 (34%) had detectable viral load and 17 (10.5%) had immunological failure at one year after recruitment
Multivariate logistic regression with boost stepwise multiple cross validation (MCV) had higher area under the curve (AUC) (0.64) compared to all univariate adherence models, except pharmacy refill adherence univariate model, which was comparable to the multivariate model (AUC = 0.64)
Summary
Optimal adherence to antiretroviral therapy is critical to prevent HIV drug resistance (HIVDR) epidemic. Where resources are available, monitoring response to combination antiretroviral therapy (ART) by virological outcome is recommended because of its strong correlation with therapy success in HIV patients. Therapy changes are guided by genotypic resistance testing. It has been shown that relying on such clinical and immunological criteria to change therapy can cause high levels of HIV drug resistance (HIVDR), compromising the line of therapy [2,3]. It is, important to identify affordable proxy markers for response to therapy in RLS. There is sufficient international evidence to support that adherence to combination ART is a major predictor of viral suppression [4,5], HIVDR [6,7], CD4 T lymphocytes count recovery [8] and survival [5,8,9]
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