Misclassification of First-Line Antiretroviral TreatmentFailure Based on Immunological Monitoring of HIVInfection in Resource-Limited Settings

Abstract

he monitoring of patients with human immunodeficiency virus (HIV) infection who are treatedwith antiretroviral medications in resource-limited settings is typically performed by use of clinical and immu-nological criteria. The early identification of first-line antiretroviral treatment failure is critical to prevent morbidity,mortality, and drug resistance. Misclassification of failure may result in premature switching to second-line therapy.Methods.Adult patients in western Kenya had their viral loads (VLs) determined if they had adhered to first-line therapy for16 months and were suspected of experiencing immunological failure (ie, their CD4 cell countdecreased by 25% in 6 months). Misclassification of treatment failure was defined as a 25% decrease in CD4cell count with a VL of!400 copies/mL. Logistic and tree regressions examined relationships between VL and 4variables: CD4 T cell count (hereafter CD4 cell count), percentage of T cells expressing CD4 (hereafter CD4 cellpercentage), percentage decrease in the CD4 T cell count (hereafter CD4 cell count percent decrease), and percentagedecrease in the percentage of T cells expressing CD4 (hereafter CD4% percent decrease).Results.There were 149 patients who were treated for 23 months; they were identified as having a 25%decrease in CD4 cell count (from 375 to 216 cells/mL) and a CD4% percent decrease (from 19% to 15%); of these149 patients, 86 (58%) were misclassified as having experienced treatment failure. Of 42 patients who had a 50%decrease in CD4 cell count, 18 (43%) were misclassified. In multivariate logistic regression, misclassification oddswere associated with a higher CD4 cell count, a shorter duration of therapy, and a smaller CD4% percent decrease.By combining these variables, we may be able to improve our ability to predict treatment failure.Conclusions.Immunological monitoring as a sole indicator of virological failure would lead to a prematureswitch to valuable second-line regimens for 58% of patients who experience a 25% decrease in CD4 cell countand for 43% patients who experience a 50% decrease in CD4 cell count, and therefore this type of monitoringshould be reevaluated. Selective virological monitoring and the addition of indicators like trends CD4% percentdecrease and duration of therapy may systematically improve the identification of treatment failure. VL testing isnow mandatory for patients suspected of experiencing first-line treatment failure within the Academic ModelProviding Access to Healthcare (AMPATH) in western Kenya, and should be considered in all resource-limitedsettings.In 2006,∼700,000 people worldwide who were infecte