title: Predictors of Treatment Failure in HIV-Positive Children Receiving Combination Antiretroviral Therapy: Cohort Data From Mozambique and Uganda.
abstract: BACKGROUND
  Delays detecting treatment failure and switching to second-line combination antiretroviral therapy (cART) are often observed in human immunodeficiency virus (HIV)-infected children of low-middle-income countries (LMIC).
  
  
  METHODS
  An observational study included HIV-infected children attending the Beira Central Hospital (Mozambique) and the Nsambya Hospital, Home Care Department (Uganda) evaluated clinical and immunological failure according to World Health Organization (WHO) 2006 guidelines. Baseline predictors for cART failure and for drug substitution were explored in unadjusted and adjusted Cox proportional hazard models.
  
  
  RESULTS
  Two hundred eighteen of 740 children with at least 24 weeks follow-up experienced treatment failure (29%; 95% confidence interval [CI] 26-33), with crude incidence of 20.0 events per 100 person-years (95% CI 17.5-22.9). Having tuberculosis co-infection or WHO stage 4, or starting a nontriple cART significantly increased risk of failure. Two hundred two of 769 (26.3%) children receiving cART substituted drug(s), with crude incidence of 15.4 events per 100 person-years (95% CI 13.4-17.7). Drug toxicity (18.3%), drug availability (17.3%), and tuberculosis drugs interaction (52, 25.7%) were main reported reasons, while only 9 (4%) patients switched cART for clinical or immunological failure. Children starting lamivudine-zidovudine-nevirapine or lamivudine-stavudine-efavirenz or lamivudine-zidovudine-efavirenz were more likely to have substitute drugs. Increased substitution was found in children with mild immunosuppression and tuberculosis co-infection at cART initiation as well as poor adherence before drug substitution.
  
  
  CONCLUSIONS
  Considerable delay in switching to second-line cART may occur despite an observed high rate of failure. Factors including WHO clinical stage and tuberculosis co-infection should be evaluated before starting cART. Toxicity and drug adherence should be monitored to minimize drug substitution in LMIC.
authors.affiliation: Department of Pediatrics, University of Padova, Italy;
authors.forename: Paola
authors.initials: P
authors.lastname: Costenaro
authors.affiliation: Department of Pediatrics, University of Padova, Italy;
authors.forename: Martina
authors.initials: M
authors.lastname: Penazzato
authors.affiliation: Department of Pediatrics, University of Padova, Italy;
authors.forename: Rebecca
authors.initials: R
authors.lastname: Lundin
authors.affiliation: Department of Pediatrics, University of Padova, Italy;
authors.forename: Giuliana
authors.initials: G
authors.lastname: Rossi
authors.affiliation: Department of Pediatrics, University of Padova, Italy; St. Raphael of St. Francis Nsambya Hospital, Kampala, Uganda;
authors.forename: William
authors.initials: W
authors.lastname: Massavon
authors.affiliation: Department of Pediatrics, University of Padova, Italy;
authors.forename: Deven
authors.initials: D
authors.lastname: Patel
authors.affiliation: St. Raphael of St. Francis Nsambya Hospital, Kampala, Uganda;
authors.forename: Sandra
authors.initials: S
authors.lastname: Nabachwa
authors.affiliation: Department of Pediatrics, University of Padova, Italy;
authors.forename: Genny
authors.initials: G
authors.lastname: Franceschetto
authors.affiliation: Department of Pediatrics, University of Padova, Italy;
authors.forename: Erika
authors.initials: E
authors.lastname: Morelli
authors.affiliation: Department of Pediatrics, University of Padova, Italy;
authors.forename: Davide
authors.initials: D
authors.lastname: Bilardi
authors.affiliation: St. Raphael of St. Francis Nsambya Hospital, Kampala, Uganda;
authors.forename: Maria Musoke
authors.initials: MM
authors.lastname: Nannyonga
authors.affiliation: Doctors With Africa CUAMM, Padova, Italy;
authors.forename: Andrea
authors.initials: A
authors.lastname: Atzori
authors.affiliation: Doctors With Africa CUAMM, Padova, Italy;
authors.forename: Maria L
authors.initials: ML
authors.lastname: Mastrogiacomo
authors.affiliation: Associazione Casa Accoglienza alla Vita Padre Angelo, Trento, Italy.
authors.forename: Antonio
authors.initials: A
authors.lastname: Mazza
authors.affiliation: Doctors With Africa CUAMM, Padova, Italy;
authors.forename: Giovanni
authors.initials: G
authors.lastname: Putoto
authors.affiliation: Department of Pediatrics, University of Padova, Italy;
authors.forename: Carlo
authors.initials: C
authors.lastname: Giaquinto
mesh_terms: D044966:Anti-Retroviral Agents / Q000627:therapeutic use*; D002648:Child; D002675:Child, Preschool; D057915:Drug Substitution; D005260:Female; D005500:Follow-Up Studies; D015658:HIV Infections / Q000150:complications / Q000175:diagnosis / Q000188:drug therapy* / Q000453:epidemiology*; D006801:Humans; D015994:Incidence; D007223:Infant; D008297:Male; D009073:Mozambique / Q000453:epidemiology; D011379:Prognosis; D016016:Proportional Hazards Models; D012189:Retrospective Studies; D017211:Treatment Failure; D014376:Tuberculosis / Q000150:complications / Q000175:diagnosis / Q000188:drug therapy / Q000453:epidemiology; D014454:Uganda / Q000453:epidemiology
chemical_list: D044966:Anti-Retroviral Agents
keywords: HIV; children; drug substitution; treatment failure.