title: Safety and efficacy of zinc supplementation for children with HIV-1 infection in South Africa: a randomised double-blind placebo-controlled trial.
abstract: BACKGROUND
  Zinc deficiency is associated with impaired immune function and an increased risk of infection. Supplementation can decrease the incidence of diarrhoea and pneumonia in children in resource-poor countries. However, in children with HIV-1 infection, the safety of zinc supplementation is uncertain. We aimed to assess the role of zinc in HIV-1 replication before mass zinc supplementation is recommended in regions of high HIV-1 prevalence.
  
  
  METHODS
  We did a randomised double-blind placebo-controlled equivalence trial of zinc supplementation at Grey's Hospital in Pietermaritzburg, South Africa. 96 children with HIV-1 infection were randomly assigned to receive 10 mg of elemental zinc as sulphate or placebo daily for 6 months. Baseline measurements of plasma HIV-1 viral load and the percentage of CD4+ T lymphocytes were established at two study visits before randomisation, and measurements were repeated 3, 6, and 9 months after the start of supplementation. The primary outcome measure was plasma HIV-1 viral load. Analysis was per protocol.
  
  
  RESULTS
  The mean log(10) HIV-1 viral load was 5.4 (SD 0.61) for the placebo group and 5.4 (SD 0.66) for the zinc-supplemented group 6 months after supplementation began (difference 0.0002, 95% CI -0.27 to 0.27). 3 months after supplementation ended, the corresponding values were 5.5 (SD 0.77) and 5.4 (SD 0.61), a difference of 0.05 (-0.24 to 0.35). The mean percentage of CD4+ T lymphocytes and median haemoglobin concentrations were also similar between the two groups after zinc supplementation. Two deaths occurred in the zinc supplementation group and seven in the placebo group (p=0.1). Children given zinc supplementation were less likely to get watery diarrhoea than those given placebo. Watery diarrhoea was diagnosed at 30 (7.4%) of 407 clinic visits in the zinc-supplemented group versus 65 (14.5%) of 447 visits in the placebo group (p=0.001).
  
  
  CONCLUSIONS
  Zinc supplementation of HIV-1-infected children does not result in an increase in plasma HIV-1 viral load and could reduce morbidity caused by diarrhoea.
  
  
  CONCLUSIONS
  Programmes to enhance zinc intake in deficient populations with a high prevalence of HIV-1 infection can be implemented without concern for adverse effects on HIV-1 replication. In view of the reductions in diarrhoea and pneumonia morbidity, zinc supplementation should be used as adjunct therapy for children with HIV-1 infection.
authors.affiliation: Department of Paediatrics and Child Health, Nelson R Mandela School of Medicine, University of KwaZulu-Natal, Durban, South Africa.
authors.forename: Raziya
authors.initials: R
authors.lastname: Bobat
authors.forename: Hoosen
authors.initials: H
authors.lastname: Coovadia
authors.forename: Cindy
authors.initials: C
authors.lastname: Stephen
authors.forename: Kimesh L
authors.initials: KL
authors.lastname: Naidoo
authors.forename: Neil
authors.initials: N
authors.lastname: McKerrow
authors.forename: Robert E
authors.initials: RE
authors.lastname: Black
authors.forename: William J
authors.initials: WJ
authors.lastname: Moss
mesh_terms: D018791:CD4 Lymphocyte Count; D002648:Child; D002675:Child, Preschool; D003967:Diarrhea / Q000209:etiology / Q000517:prevention & control; D004311:Double-Blind Method; D005260:Female; D015658:HIV Infections / Q000150:complications / Q000188:drug therapy* / Q000401:mortality; D015497:HIV-1; D006801:Humans; D007223:Infant; D008297:Male; D013019:South Africa; D019562:Viral Load; D015032:Zinc / Q000172:deficiency / Q000627:therapeutic use*
chemical_list: D015032:Zinc