title: 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/microL) 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.
authors: Division of Infectious Diseases, Brown University, Providence, Rhode Island, USA. rkantor@brown.edu
authors: Rami
authors: R
authors: Kantor
authors: Lameck
authors: L
authors: Diero
authors: Allison
authors: A
authors: Delong
authors: Lydia
authors: L
authors: Kamle
authors: Sarah
authors: S
authors: Muyonga
authors: Fidelis
authors: F
authors: Mambo
authors: Eunice
authors: E
authors: Walumbe
authors: Wilfred
authors: W
authors: Emonyi
authors: Philip
authors: P
authors: Chan
authors: E Jane
authors: EJ
authors: Carter
authors: Joseph
authors: J
authors: Hogan
authors: Nathan
authors: N
authors: Buziba
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D019380:Anti-HIV Agents / Q000627:therapeutic use*; D018791:CD4 Lymphocyte Count; D016516:CD4-CD8 Ratio; D003951:Diagnostic Errors; D005260:Female; D006678:HIV / Q000187:drug effects*; D015658:HIV Infections / Q000188:drug therapy* / Q000276:immunology* / Q000821:virology; D006801:Humans; D007630:Kenya; D008297:Male; D008875:Middle Aged; D015166:Monitoring, Immunologic / Q000379:methods*; D017211:Treatment Failure; D019562:Viral Load; D055815:Young Adult
chemical_list: D019380:Anti-HIV Agents