title: Effects of postnatal interventions for the reduction of vertical HIV transmission on infant growth and non-HIV infections: a systematic review.
abstract: BACKGROUND
  Guidelines in resource-poor settings have progressively included interventions to reduce postnatal HIV transmission through breast milk. In addition to HIV-free survival, infant growth and non-HIV infections should be considered. Determining the effect of these interventions on infant growth and non-HIV infections will inform healthcare decisions about feeding HIV-exposed infants. We synthesize findings from studies comparing breast to formula feeding, early weaning to standard-duration breastfeeding, breastfeeding with extended antiretroviral (ARV) to short-course ARV prophylaxis, and alternative preparations of infant formula to standard formula in HIV-exposed infants, focusing on infant growth and non-HIV infectious morbidity outcomes. The review objectives were to collate and appraise evidence of interventions to reduce postnatal vertical HIV transmission, and to estimate their effect on growth and non-HIV infections from birth to two years of age among HIV-exposed infants.
  
  
  METHODS
  We searched PubMed, SCOPUS, and Cochrane CENTRAL Controlled Trials Register. We included randomized trials and prospective cohort studies. Two authors independently extracted data and evaluated risk of bias. Rate ratios and mean differences were used as effect measures for dichotomous and continuous outcomes, respectively. Where pooling was possible, we used fixed-effects meta-analysis to pool results across studies. Quality of evidence was assessed using the GRADE approach.
  
  
  CONCLUSIONS
  Prospective cohort studies comparing breast- versus formula-fed HIV-exposed infants found breastfeeding to be protective against diarrhoea in early life [risk ratio (RR)=0.31; 95% confidence interval (CI)=0.13 to 0.74]. The effect of breastfeeding against diarrhoea [hazard ratio (HR)=0.74; 95% CI=0.57 to 0.97] and respiratory infections (HR=0.65; 95% CI=0.41 to 1.00) was significant through two years of age. The only randomized controlled trial (RCT) available showed that breastfeeding tended to be protective against malnutrition (RR=0.63; 95% CI=0.36 to 1.12). We found no statistically significant differences in the rates of non-HIV infections or malnutrition between breast-fed infants in the extended and short-course ARV prophylaxis groups.
  
  
  CONCLUSIONS
  Low to moderate quality evidence suggests breastfeeding may improve growth and non-HIV infection outcomes of HIV-exposed infants. Extended ARV prophylaxis does not appear to increase the risk for HIV-exposed infants for adverse growth or non-HIV infections compared to short-course ARV prophylaxis.
authors.affiliation: Department of Paediatrics and Child Health, Children's Infectious Disease Clinical Research Unit, Stellenbosch University, Tygerberg, South Africa; moleenzunza@ymail.com.
authors.forename: Moleen
authors.initials: M
authors.lastname: Zunza
authors.affiliation: MD/PhD Program, Faculty of Medicine, University of British Columbia, Vancouver, British Columbia, Canada.
authors.forename: Gareth D
authors.initials: GD
authors.lastname: Mercer
authors.affiliation: Department of Clinical Epidemiology and Biostatistics, McMaster University, Hamilton, Ontario, Canada; Biostatistics Unit/FSORC, St Joseph's Healthcare Hamilton, Hamilton, Ontario, Canada.
authors.forename: Lehana
authors.initials: L
authors.lastname: Thabane
authors.affiliation: Department of Pathology, Immunology Unit, NHLS, Stellenbosch University, Tygerberg, South Africa.
authors.forename: Monika
authors.initials: M
authors.lastname: Esser
authors.affiliation: Department of Paediatrics and Child Health, Children's Infectious Disease Clinical Research Unit, Stellenbosch University, Tygerberg, South Africa.
authors.forename: Mark F
authors.initials: MF
authors.lastname: Cotton
mesh_terms: D019380:Anti-HIV Agents / Q000627:therapeutic use; D001942:Breast Feeding; D015331:Cohort Studies; D015658:HIV Infections / Q000517:prevention & control* / Q000635:transmission*; D006801:Humans; D007223:Infant; D041943:Infant Formula; D018445:Infectious Disease Transmission, Vertical / Q000517:prevention & control*; D011181:Postnatal Care / Q000379:methods*; D011446:Prospective Studies; D016032:Randomized Controlled Trials as Topic
chemical_list: D019380:Anti-HIV Agents
keywords: HIV; breast milk; children; growth; non-HIV infections; postnatal interventions