Elsevier

Nutrition

Volume 21, Issue 1, January 2005, Pages 25-31
Nutrition

Applied nutritional investigation
Effect of periodic vitamin A supplementation on mortality and morbidity of human immunodeficiency virus–infected children in Uganda: A controlled clinical trial

https://doi.org/10.1016/j.nut.2004.10.004Get rights and content

Abstract

Objective

We investigated whether vitamin A supplementation would decrease mortality and morbidity rates in children infected with the human immunodeficiency virus (HIV).

Methods

We conducted a randomized, double-blind, placebo-controlled clinical trial at Mulago Hospital, a large hospital that serves the urban and semiurban populations of Kampala, Uganda. One hundred eighty-one HIV-infected children were enrolled at 6 mo and randomized to receive vitamin A supplementation, 60 mg retinol equivalent, or placebo every 3 mo from ages 15 to 36 mo. Morbidity was assessed through a 7-d morbidity history every 3 mo, and vital events were measured. Children received daily trimethoprim-sulfamethoxazole prophylactic therapy.

Results

After age 15 mo, children were followed for a median of 17.8 mo (interquartile range = 11.1 to 21.0 mo). The trial was stopped when there was a new policy to implement a program of mass supplementation of vitamin A in the country. Mortality rates among 87 children in the vitamin A group and 94 children in the control group were 20.6% and 32.9%, respectively, yielding a relative risk of 0.54 (95% confidence interval, 0.30 to 0.98; P = 0.044) after adjusting for baseline weight-for-height Z score. Children who received vitamin A had lower modified point prevalences of persistent cough (odds ratio, 0.47; 95% confidence interval, 0.23 to 0.96; P = 0.038) and chronic diarrhea (odds ratio, 0.48; 95% confidence interval, 0.19 to 1.18; P = 0.11) and a shorter duration of ear discharge (P = 0.03). Vitamin A supplementation had no significant effect on modified point prevalences of fever, ear discharge, bloody stools, or hospitalizations.

Conclusions

Vitamin A supplementation decreases mortality rate in HIV-infected children and should be considered in the care for these children in developing countries.

Introduction

About 700,000 infants are infected with human immunodeficiency virus (HIV) each year through transmission from mother to child, and most of these infants are found in sub-Saharan Africa [1], [2]. Currently it is estimated that there are 2.5 million children living with HIV worldwide [2]. In developing countries, vitamin A deficiency may be common in areas with a high prevalence of HIV infection [3]. Vitamin A is essential for normal immune function [4], and vitamin A deficiency has been associated with increased progression to acquired immunodeficiency syndrome and increased mortality rates in HIV infection [3]. Since the 1920s, vitamin A was known as the “anti-infective” vitamin, and vitamin A supplementation was recognized for its ability to decrease morbidity and mortality rates from some infectious diseases [5]. Recent trials have shown that vitamin A supplementation decreases morbidity and mortality rates from diarrheal disease [6] and decreases morbidity from malaria [7] among preschool children. Vitamin A supplementation has been shown to decrease the mortality rate from acute, complicated measles among infants and young children by about 50% to 75% [6]. Appropriate, low-cost interventions are needed that will improve the health and survival of HIV-infected children in developing countries, and it is unclear whether vitamin A supplementation, an inexpensive therapy, could decrease the mortality rate of HIV-infected children. We hypothesized that large-dose vitamin A supplementation every 3 mo would increase survival rates in HIV-infected children. To address this hypothesis, we conducted a randomized, double-blind, controlled clinical trial in Kampala, Uganda.

Section snippets

Materials and methods

The study population consisted of 181 15-mo-old HIV-infected children seen at Mulago Hospital in Kampala, Uganda. The population served by Mulago Hospital is primarily from the urban and semiurban regions of Kampala (population 1.2 million). Clinical vitamin A deficiency, as manifested by night blindness, Bitot's spots, corneal xerosis, or more severe ocular findings, is relatively uncommon in Kampala. There have been no cases of clinical vitamin A deficiency among infants and children reported

Results

From January 1995 to June 1998, 23,439 pregnant women were screened for HIV-1 antibody at Mulago Hospital, and 3751 (16%) were found to be positive for HIV. At ages 3 to 5 mo, 1677 infants were screened for HIV infection. Three hundred infants considered to be infected with HIV were enrolled at age 6 mo, but 29 infants who were originally diagnosed as having HIV on the basis of the p24 antigen assay were found to be negative by the HIV-1 RNA PCR assay. Thus, 271 HIV-infected infants were

Discussion

In this study, high-dose vitamin A supplementation every 3 mo decreased the mortality rate of HIV-infected children by 46%. Three previous studies have suggested that vitamin A supplementation may have promise for HIV-infected children. In Durban, South Africa, periodic, high-dose vitamin A supplementation appeared to decrease diarrheal morbidity among infants born to HIV-infected mothers, but in a stratified analysis of the 28 HIV-positive infants in the trial, the beneficial effect did not

Acknowledgments

The authors thank Esther Aceng, MD, Israel Kalyesubula, MD, Joseph Sherman, MD, and Maxie Owor, MD, Henry Tumwijukye, administrator, and the physicians, nurses, and staff of the Makerere University–Johns Hopkins Research Collaboration. They thank Anne Willoughby, Robert Nugent, and Kenneth Bridbord at the National Institutes of Health for encouragement and support. They thank these members of the data and safety monitoring committee: Fred Wabwire-Mangen, Institute for Public Health, Makerere

References (25)

  • G.H. Beaton et al.

    Effectiveness of vitamin A supplementation in the control of young child morbidity and mortality in developing countries. ACC/SCN state-of-the-art nutrition policy discussion paper no. 13

    (1993)
  • W.W. Fawzi et al.

    A randomized trial of vitamin A supplements in relation to mortality among human immunodeficiency virus-infected and uninfected children in Tanzania

    Pediatr Infect Dis J

    (1999)
  • Cited by (0)

    This study was supported by the National Institutes of Health (HD30042, HD32247) and the Fogarty International Center.

    View full text