title: Prevention of diarrhoea in children with HIV infection or exposure to maternal HIV infection.
abstract: BACKGROUND
  Diarrhoea is a major cause of morbidity and mortality among infants and children worldwide, especially in low- and middle-income countries. Human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS) is a condition that similarly disproportionately affects low- and middle-income countries; of the nearly 2.1 million children under age 15 years living with HIV/AIDS, the large majority reside in sub-Saharan Africa. Infants and children with HIV infection have more frequent and more severe diarrhoea than children without HIV. Interventions including vitamin A, zinc and cotrimoxazole may contribute substantially to preventing diarrhoea in children with HIV infection or exposure to HIV.
  
  
  OBJECTIVE
  We perform a systematic review of randomised controlled trials and nonrandomised studies that examine the effectiveness of vitamin A, zinc and cotrimoxazole on mortality and morbidity from diarrhoea in HIV-infected and -exposed infants and children.
  
  
  METHODS
  Electronic databases including Pubmed, Central and EMBASE were searched without limits to language from 1980 to April 2010. Conference database searches were performed, experts were contacted and bibliographies were handsearched.
  
  
  METHODS
  Randomised controlled trials (RCTs) and nonrandomised studies (NRSs) that examined the effectiveness of the three interventions were included.
  
  
  METHODS
  Two reviewers independently assessed citations for eligibility and double-extracted included studies. Assessment of bias of individual studies was performed independently by both reviewers. Only two summary estimates were performed due to heterogeneity in study design and interventions.
  
  
  RESULTS
  Four RCTs were identified for vitamin A. One RCT was identified for zinc. One RCT and two NRSs were identified for cotrimoxazole. Vitamin A reduced mortality overall in children with HIV infection (four studies). A pooled estimate of three studies for reduction in mortality from vitamin A compared to placebo had a relative risk (DerSimonian and Laird method, random effects) of 0.50 (95% confidence interval (CI): 0.31 to 0.79) in 267 patients. Diarrheoa-specific mortality did not reach statistical significance and diarrhoeal morbidity outcomes were variable in three trials. Zinc supplementation reduced the number of physician visits for watery diarrhoea in one trial. Cotrimoxazole reduced mortality and hospitalisations compared to placebo in one RCT, although diarrhoea-specific morbidities were not significant.
  
  
  CONCLUSIONS
  Vitamin A shows benefits in reduction of mortality in HIV-infected children. The effect of vitamin A on children with HIV exposure is not clear and needs further review. Zinc and combination vitamin A, zinc and micronutrient supplementation did not show an effect compared to vitamin A alone in children with HIV infection. Cotrimoxazole reduced mortality and some morbidity in children with HIV infection. Further research may clarify the effects of these interventions on morbidity from diarrhoea and in the population of children with HIV exposure.
authors.affiliation: Global Health Sciences, University of California, San Francisco, 50 Beale Street, Suite 1200, San Francisco, California, USA, 94105.
authors.forename: Eliza H
authors.initials: EH
authors.lastname: Humphreys
authors.forename: Nathan A
authors.initials: NA
authors.lastname: Smith
authors.forename: Hana
authors.initials: H
authors.lastname: Azman
authors.forename: Deanna
authors.initials: D
authors.lastname: McLeod
authors.forename: George W
authors.initials: GW
authors.lastname: Rutherford
mesh_terms: D000890:Anti-Infective Agents / Q000627:therapeutic use; D001942:Breast Feeding / Q000009:adverse effects; D002648:Child; D003967:Diarrhea / Q000401:mortality / Q000517:prevention & control*; D005260:Female; D015658:HIV Infections / Q000150:complications* / Q000401:mortality / Q000635:transmission; D006801:Humans; D007223:Infant; D018445:Infectious Disease Transmission, Vertical; D018977:Micronutrients / Q000627:therapeutic use; D011247:Pregnancy; D011251:Pregnancy Complications, Infectious; D016032:Randomized Controlled Trials as Topic; D015662:Trimethoprim, Sulfamethoxazole Drug Combination / Q000627:therapeutic use; D014801:Vitamin A / Q000627:therapeutic use; D014815:Vitamins / Q000627:therapeutic use; D015032:Zinc / Q000008:administration & dosage / Q000172:deficiency
chemical_list: D000890:Anti-Infective Agents; D018977:Micronutrients; D014815:Vitamins; D014801:Vitamin A; D015662:Trimethoprim, Sulfamethoxazole Drug Combination; D015032:Zinc