Zinc supplementation in children with HIV-1 infection

Abstract

We welcome the publication of Raziya Bobat and colleagues' randomised trial of zinc supplementation in HIV-1-infected South African children (Nov 26, p 1862);1Bobat R Coovadia H Stephen C et al.Safety and efficacy of zinc supplementation for children with HIV-1 infection in South Africa: a randomised double-blind placebo-controlled trial.Lancet. 2005; 366: 1862-1867Summary Full Text Full Text PDF PubMed Scopus (121) Google Scholar it adds much to a neglected area of nutritional research. However, we feel their conclusion that zinc supplementation should be used as an adjunct therapy for children with HIV-1 infection is not entirely justified by the data. The study was principally designed and powered as a safety study, with the aim of excluding an increase in viral load in the zinc group (specified as the primary endpoint). Although efficacy was suggested by a significant reduction in the proportion of clinic visits caused by watery diarrhoea (frequency of new diarrhoea episodes was not reported) and a modest advantage in bodyweight (not sustained) in the zinc supplementation group, these outcomes were apparently not specified a-priori as secondary endpoints and should be interpreted with caution in view of the multiple analyses done. There was no significant reduction in viral load, no increase in percentage CD4 count, no decrease in frequency of opportunistic infections, and no decrease in overall mortality; these are the normal outcome variables by which the efficacy of HIV treatments are judged. Larger clinical-endpoint studies are required to confirm the preliminary efficacy findings of this study. Furthermore, the trial was done in children who were not receiving antiretroviral therapy (ART), although, as Bobat and colleagues point out, 40% would have been eligible for such treatment. ART is known to result in major improvements in morbidity and mortality, and some observational data suggest that it might also reduce zinc deficiency, possibly obviating the need for specific supplementation.2Rousseau M Molines C Moreau J Delmont J Influence of highly active antiretroviral therapy on micronutrient profiles in HIV-infected patients.Ann Nutr Metab. 2000; 44: 212-216Crossref PubMed Scopus (49) Google Scholar Whether zinc supplementation provides any additional benefit over and above that of ART is uncertain. No trial has been done in children, but our randomised controlled trial of zinc supplementation in adults taking ART showed no benefits with respect to immune response to tuberculosis, CD4 counts, and viral load.3Green JA Lewin SR Wightman F Lee M Ravindran S Paton NI A randomised placebo-controlled trial to assess oral zinc supplementation and the immune response to tuberculosis in HIV infected patients.Int J Tuberc Lung Dis. 2005; 9: 1378-1384PubMed Google Scholar Even though malnutrition (in the form of low bodyweight) remains an important prognostic factor in patients starting ART,4Severe P Leger P Charles M et al.Antiretroviral therapy in a thousand patients with AIDS in Haiti.N Engl J Med. 2005; 353: 2325-2334Crossref PubMed Scopus (233) Google Scholar the advantages of specific macronutrient and micronutrient supplementation regimens must be proven in large-scale randomised controlled trials in patients taking ART before they can be recommended as routine adjunctive therapy. Although Bobat and colleagues' study showed that zinc supplementation was safe, the recommendation to use zinc treatment in HIV-1 infected children might not be so innocuous. In many underdeveloped countries where access to ART is not yet widespread, limited financial resources, infrastructure, and trained manpower represent major barriers to scale-up and implementation of ART programmes. Diversion of such resources to deliver interventions for HIV-1-infected children that are unproven and undeniably less effective than ART might prove counter-productive. We declare that we have no conflict of interest. Zinc supplementation in children with HIV-1 infection – Authors' replyOur study was principally designed to assess the safety of zinc supplementation for children with HIV-1 infection, but its effect on morbidity (particularly diarrhoea and respiratory tract infections) and mortality were explicit secondary outcomes. Full-Text PDF