title: CD4+ gain percentile curves for monitoring response to antiretroviral therapy in HIV-infected adults.
abstract: OBJECTIVE
  We constructed CD4 cell count gain percentile distributions standardized by baseline CD4 cell count and assessed the association between poor CD4 cell count gain and subsequent death and virological failure on antiretroviral therapy (ART).
  
  
  METHODS
  Secondary analysis of 10 years of clinical data from a cohort of adults initiated on ART at the Themba Lethu clinic in Johannesburg, South Africa.
  
  
  METHODS
  The generalized additive model for location, scale and shape was used to construct percentile curves for CD4 cell count gain standardized by baseline CD4 cell count in the first 28 months of ART. Cox proportional models were used to assess the association between lower percentiles (<50th) of CD4 cell count gain, and subsequent death and virological failure.
  
  
  RESULTS
  Among 9640 nonpregnant adults 7406, with available CD4 cell count results for CD4 gain calculation at 4 months of ART, 843 (8.7%) died subsequently and 1101 (11.4%) experienced virologic failure, respectively. For CD4 gains below the third percentile, the adjusted hazard ratios at different time points ranged between 2.72 and 5.73 for death, and between 1.48 and 6.93 for virologic failure. The CD4 percentile curves revealed a gradient of increasing risk of subsequent death and virological failure, with lower CD4 gain percentiles and increasing time on ART, and were more informative than the WHO criteria for immunological failure or current CD4 cell count.
  
  
  CONCLUSIONS
  Percentile curves of CD4 cell count gain provide a simple tool for healthcare workers in low-resource settings to monitor response to ART with improved information regarding risk of death and virological failure compared to current WHO criteria for immunological failure.
authors.affiliation: aThe Ohio State University, College of Public Health, Division of Epidemiology, Columbus, Ohio bThe University of North Carolina at Chapel Hill, Department of Epidemiology, Chapel Hill, North Carolina, USA cDepartment of Medicine, Clinical HIV Research Unit, University of the Witwatersrand, Johannesburg, South Africa.
authors.forename: Marcel
authors.initials: M
authors.lastname: Yotebieng
authors.forename: Mhairi
authors.initials: M
authors.lastname: Maskew
authors.forename: Annelies
authors.initials: A
authors.lastname: Van Rie
mesh_terms: D000293:Adolescent; D000328:Adult; D044966:Anti-Retroviral Agents / Q000627:therapeutic use*; D023241:Antiretroviral Therapy, Highly Active / Q000379:methods*; D018791:CD4 Lymphocyte Count; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D015331:Cohort Studies; D016903:Drug Monitoring; D005260:Female; D015658:HIV Infections / Q000188:drug therapy* / Q000276:immunology; D006801:Humans; D008297:Male; D008875:Middle Aged; D013019:South Africa; D016019:Survival Analysis; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D044966:Anti-Retroviral Agents