Safety and efficacy of zinc supplementation for children with HIV-1 infection in South Africa: A randomised double-blind placebo-controlled trial

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. Findings: The mean log10 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). Interpretation. 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. Relevance to Practice: 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.