title: Clinical, Virologic, Immunologic Outcomes and Emerging HIV Drug Resistance Patterns in Children and Adolescents in Public ART Care in Zimbabwe.
abstract: OBJECTIVE
  To determine immunologic, virologic outcomes and drug resistance among children and adolescents receiving care during routine programmatic implementation in a low-income country.
  
  
  METHODS
  A cross-sectional evaluation with collection of clinical and laboratory data for children (0-<10 years) and adolescents (10-19 years) attending a public ART program in Harare providing care for pediatric patients since 2004, was conducted. Longitudinal data for each participant was obtained from the clinic based medical record.
  
  
  RESULTS
  Data from 599 children and adolescents was evaluated. The participants presented to care with low CD4 cell count and CD4%, median baseline CD4% was lower in adolescents compared with children (11.0% vs. 15.0%, p<0.0001). The median age at ART initiation was 8.0 years (IQR 3.0, 12.0); median time on ART was 2.9 years (IQR 1.7, 4.5). On ART, median CD4% improved for all age groups but remained below 25%. Older age (≥ 5 years) at ART initiation was associated with severe stunting (HAZ <-2: 53.3% vs. 28.4%, p<0.0001). Virologic failure rate was 30.6% and associated with age at ART initiation. In children, nevirapine based ART regimen was associated with a 3-fold increased risk of failure (AOR: 3.5; 95% CI: 1.3, 9.1, p = 0.0180). Children (<10 y) on ART for ≥4 years had higher failure rates than those on ART for <4 years (39.6% vs. 23.9%, p = 0.0239). In those initiating ART as adolescents, each additional year in age above 10 years at the time of ART initiation (AOR 0.4 95%CI: 0.1, 0.9, p = 0.0324), and each additional year on ART (AOR 0.4, 95%CI 0.2, 0.9, p = 0.0379) were associated with decreased risk of virologic failure. Drug resistance was evident in 67.6% of sequenced virus isolates.
  
  
  CONCLUSIONS
  During routine programmatic implementation of HIV care for children and adolescents, delayed age at ART initiation has long-term implications on immunologic recovery, growth and virologic outcomes.
authors.affiliation: Ragon Institute of MGH, MIT and Harvard, Cambridge, Massachusetts, United States of America.|Department of Medicine, University of Zimbabwe College of Health Sciences, Harare, Zimbabwe.
authors.forename: A T
authors.initials: AT
authors.lastname: Makadzange
authors.affiliation: John Snow Inc, Boston, Massachusetts, United States of America.
authors.forename: M
authors.initials: M
authors.lastname: Higgins-Biddle
authors.affiliation: Department of Medicine, University of Zimbabwe College of Health Sciences, Harare, Zimbabwe.|African Institute of Biomedical Sciences, Harare, Zimbabwe.
authors.forename: B
authors.initials: B
authors.lastname: Chimukangara
authors.affiliation: Department of Medicine, University of Zimbabwe College of Health Sciences, Harare, Zimbabwe.
authors.forename: R
authors.initials: R
authors.lastname: Birri
authors.affiliation: HIV Pathogenesis Program, University of Kwa-Zulu Natal, Durban, South Africa.
authors.forename: M
authors.initials: M
authors.lastname: Gordon
authors.affiliation: Department of Medicine, University of Zimbabwe College of Health Sciences, Harare, Zimbabwe.
authors.forename: T
authors.initials: T
authors.lastname: Mahlanza
authors.affiliation: Department of Medicine, University of Zimbabwe College of Health Sciences, Harare, Zimbabwe.
authors.forename: G
authors.initials: G
authors.lastname: McHugh
authors.affiliation: Department of Medicine, University of Zimbabwe College of Health Sciences, Harare, Zimbabwe.
authors.forename: J H
authors.initials: JH
authors.lastname: van Dijk
authors.affiliation: Department of Pediatrics, University of Zimbabwe College of Health Sciences, Harare, Zimbabwe.
authors.forename: M
authors.initials: M
authors.lastname: Bwakura-Dangarembizi
authors.affiliation: HIV Pathogenesis Program, University of Kwa-Zulu Natal, Durban, South Africa.
authors.forename: T
authors.initials: T
authors.lastname: Ndung'u
authors.affiliation: African Institute of Biomedical Sciences, Harare, Zimbabwe.
authors.forename: C
authors.initials: C
authors.lastname: Masimirembwa
authors.affiliation: United States Agency for International Development (USAID), Washington, DC, United States of America.
authors.forename: B
authors.initials: B
authors.lastname: Phelps
authors.affiliation: United States Agency for International Development (USAID), Washington, DC, United States of America.
authors.forename: A
authors.initials: A
authors.lastname: Amzel
authors.affiliation: John Snow Inc, Boston, Massachusetts, United States of America.
authors.forename: B O
authors.initials: BO
authors.lastname: Ojikutu
authors.affiliation: Ragon Institute of MGH, MIT and Harvard, Cambridge, Massachusetts, United States of America.
authors.forename: B D
authors.initials: BD
authors.lastname: Walker
authors.affiliation: Department of Medicine, University of Zimbabwe College of Health Sciences, Harare, Zimbabwe.
authors.forename: C E
authors.initials: CE
authors.lastname: Ndhlovu
mesh_terms: D000293:Adolescent; D000367:Age Factors; D019380:Anti-HIV Agents / Q000627:therapeutic use*; D018791:CD4 Lymphocyte Count; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000473:pathology / Q000821:virology*; D002648:Child; D002675:Child, Preschool; D003430:Cross-Sectional Studies; D024882:Drug Resistance, Viral; D005260:Female; D015658:HIV Infections / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology / Q000821:virology; D015497:HIV-1 / Q000187:drug effects / Q000502:physiology; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D019829:Nevirapine / Q000627:therapeutic use*; D013997:Time Factors; D017211:Treatment Failure; D019562:Viral Load / Q000187:drug effects; D055815:Young Adult; D015030:Zimbabwe
chemical_list: D019380:Anti-HIV Agents; D019829:Nevirapine