Misclassification of First‐Line Antiretroviral Treatment Failure Based on Immunological Monitoring of HIV Infection in Resource‐Limited Settings

Abstract

Background The monitoring of patients with human immunodeficiency virus (HIV) infection who are treated with antiretroviral medications in resource-limited settings is typically performed by use of clinical and immunological 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 for >6 months and were suspected of experiencing immunological failure (ie, their CD4 cell count decreased by ⩾25% in 6 months). Misclassification of treatment failure was defined as a ⩾25% decrease in CD4 cell count with a VL of <400 copies/mL. Logistic and tree regressions examined relationships between VL and 4 variables: CD4 T cell count (hereafter CD4 cell count), percentage of T cells expressing CD4 (hereafter CD4 cell percentage), percentage decrease in the CD4 T cell count (hereafter CD4 cell count percent decrease), and percentage decrease 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/μL) and a CD4% percent decrease (from 19% to 15%); of these 149 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 odds were 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 premature switch to valuable second-line regimens for 58% of patients who experience a ⩾25% decrease in CD4 cell count and for 43% patients who experience a ⩾50% decrease in CD4 cell count, and therefore this type of monitoring should be reevaluated. Selective virological monitoring and the addition of indicators like trends CD4% percent decrease and duration of therapy may systematically improve the identification of treatment failure. VL testing is now mandatory for patients suspected of experiencing first-line treatment failure within the Academic Model Providing Access to Healthcare (AMPATH) in western Kenya, and should be considered in all resource-limited settings.

Predicting Virological Failure with Immunological Criteria in First Line ART Patients in a Resource Poor Setting

“…If the duration is less than 2 years and CD4 more than 200 cells/ml resulted in poor sensitivity in this study. In western Kenyan study [15] at least 58% of patients were switched to second line without virological failure with fall in CD4 count of 25% in 6 months and CD4% falling from 19% to 25%. The immunological criteria were concluded as less sensitive.…”

Extensive Drug Resistance in HIV-Infected Cambodian Children Who Are Undetected as Failing First-Line Antiretroviral Therapy by WHO 2010 Guidelines

“…Frequent misclassification of virological failure in adult patients has been reported, leading to early ART switch or late failure diagnosis. [3][4][5] In the latter circumstances, by the time treatment failure is recognized, patients may have already accumulated drug resistance mutations and high-level cross-resistance to subsequent antiretroviral regimens. [6][7][8] Minimizing resistance is particularly important in RLS with limited ART options, usually restricted to first-line nonnucleoside reverse transcriptase inhibitor (NNRTI)-based and second-line protease inhibitor (PI)-based regimens.…”

Comparison of the Effectiveness of Low-Dose Indinavir/Ritonavir (IDV/r)- versus Atazanavir/Ritonavir (ATV/r)-Based Generic Antiretroviral Therapy in NNRTI-Experienced HIV-1-Infected Patients in India

“…[22][23][24][25][26] This can lead to either delayed diagnosis of treatment failure or overdiagnosis of treatment failure. 22 In both situations, patient can have either premature change to second-line regimen or due to delayed diagnosis more drug resistance will be accumulated, compromising effectiveness of subsequent treatment. 25 …”