title: Single-dose nevirapine exposure does not affect response to antiretroviral therapy in HIV-infected African children aged below 3 years.
abstract: OBJECTIVE
  To assess the impact of exposure to single-dose nevirapine (sdNVP) on virological response in young Ugandan/Zimbabwean children (<3 years) initiating antiretroviral therapy (ART), and to investigate other predictors of response.
  
  
  METHODS
  Observational analysis within the ARROW randomized trial.
  
  
  METHODS
  sdNVP exposure was ascertained by the caregiver's self-report when the child initiated non-nucleoside reverse transcriptase inhibitor (NNRTI)-based ART. Viral load was assayed retrospectively over a median 4.1 years of follow-up. Multivariable logistic regression models were used to identify independent predictors of viral load below 80 copies/ml, 48 and 144 weeks after ART initiation (backwards elimination, exit P = 0.1).
  
  
  RESULTS
  Median (IQR) age at ART initiation was 17 (10-23) months in 78 sdNVP-exposed children vs. 21 (14-27) months in 289 non-exposed children (36 vs. 20% <12 months). At week 48, 49 of 73 (67%) sdNVP-exposed and 154 of 272 (57%) non-exposed children had viral load below 80 copies/ml [adjusted odds ratio (aOR) 2.34 (1.26-4.34), P = 0.007]; 79 and 77% had viral load below 400 copies/ml. Suppression was significantly lower in males (P = 0.009), those with higher pre-ART viral load (P = 0.001), taking syrups (P = 0.05) and with lower self-reported adherence (P = 0.04). At week 144, 55 of 73 (75%) exposed and 188 of 272 (69%) non-exposed children had less than 80 copies/ml [aOR 1.75 (0.93-3.29), P = 0.08]. There was no difference between children with and without previous sdNVP exposure in intermediate/high-level resistance to NRTIs (P > 0.3) or NNRTIs (P > 0.1) (n = 88) at week 144.
  
  
  CONCLUSIONS
  Given the limited global availability of lopinavir/ritonavir, its significant formulation challenges in young children, and the significant paediatric treatment gap, tablet fixed-dose-combination NVP-based ART remains a good alternative to syrup lopinavir-based ART for children, particularly those over 1 year and even if exposed to sdNVP.
authors.affiliation: Baylor-Uganda, Paediatric Infectious Diseases Clinic, Mulago Hospital, Kampala, Uganda; Makerere University College of Health Sciences, Kampala, Uganda.
authors.forename: Philippa
authors.initials: P
authors.lastname: Musoke
authors.affiliation: MRC Clinical Trials Unit at University College London, London, UK.
authors.forename: Alexander J
authors.initials: AJ
authors.lastname: Szubert
authors.affiliation: Joint Clinical Research Centre, Kampala, Uganda; Makerere University College of Health Sciences, Kampala, Uganda.
authors.forename: Victor
authors.initials: V
authors.lastname: Musiime
authors.affiliation: University of Zimbabwe College of Health Sciences, Harare, Zimbabwe.
authors.forename: Kusum
authors.initials: K
authors.lastname: Nathoo
authors.affiliation: Medical Research Council/Uganda Virus Research Institute Uganda Research Unit on AIDS, Entebbe, Uganda.
authors.forename: Patricia
authors.initials: P
authors.lastname: Nahirya-Ntege
authors.affiliation: Zvitambo Institute for Maternal and Child Health Research, Harare, Zimbabwe.
authors.forename: Kuda
authors.initials: K
authors.lastname: Mutasa
authors.affiliation: Joint Clinical Research Centre, Kampala, Uganda.
authors.forename: David Eram
authors.initials: DE
authors.lastname: Williams
authors.affiliation: Queen Mary University of London, London, UK.
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Prendergast
authors.affiliation: MRC Clinical Trials Unit at University College London, London, UK.
authors.forename: Moira
authors.initials: M
authors.lastname: Spyer
authors.affiliation: MRC Clinical Trials Unit at University College London, London, UK.
authors.forename: A Sarah
authors.initials: AS
authors.lastname: Walker
authors.affiliation: MRC Clinical Trials Unit at University College London, London, UK.
authors.forename: Diana M
authors.initials: DM
authors.lastname: Gibb
mesh_terms: D044966:Anti-Retroviral Agents / Q000008:administration & dosage*; D002675:Child, Preschool; D005260:Female; D015658:HIV Infections / Q000188:drug therapy* / Q000821:virology*; D006801:Humans; D007223:Infant; D008297:Male; D019829:Nevirapine / Q000008:administration & dosage*; D012189:Retrospective Studies; D016896:Treatment Outcome; D014454:Uganda; D019562:Viral Load; D015030:Zimbabwe
chemical_list: D044966:Anti-Retroviral Agents; D019829:Nevirapine