A Randomized Trial of Multivitamin Supplements and HIV Disease Progression and Mortality

Fawzi, Wafaie W.
Msamanga, Gernard I.
Spiegelman, Donna
Wei, Ruilan
Kapiga, Saidi
Villamor, Eduardo
Mwakagile, Davis
Mugusi, Ferdinand
Hertzmark, Ellen
Essex, Max
Hunter, David J.

From the Departments of Nutrition (W.W.F., R.W., E.V., D.J.H.), Epidemiology (W.W.F., D.S., E.H., D.J.H.), Biostatistics (D.S.), Population and International Health (S.K.), and Immunology and Infectious Diseases (M.E.), Harvard School of Public Health, Boston; and the Departments of Community Health (G.I.M.), Microbiology and Immunology (D.M.), and Internal Medicine (F.M.), Muhimbili University College of Health Sciences, Dar es Salaam, Tanzania. Address reprint requests to Dr. Fawzi at the Department of Nutrition, Harvard School of Public Health, 665 Huntington Ave., Boston, MA 02115, or at [email protected].

New England Journal of Medicine 351(1):p 23-32, July 1, 2004. | DOI: 10.1056/NEJMoa040541

Background

Results from observational studies suggest that micronutrient status is a determinant of the progression of human immunodeficiency virus (HIV) disease.

Methods

We enrolled 1078 pregnant women infected with HIV in a double-blind, placebo-controlled trial in Dar es Salaam, Tanzania, to examine the effects of daily supplements of vitamin A (preformed vitamin A and beta carotene), multivitamins (vitamins B, C, and E), or both on progression of HIV disease, using survival models. The median follow-up with respect to survival was 71 months (interquartile range, 46 to 80).

Results

Of 271 women who received multivitamins, 67 had progression to World Health Organization (WHO) stage 4 disease or died - the primary outcome - as compared with 83 of 267 women who received placebo (24.7 percent vs. 31.1 percent; relative risk, 0.71; 95 percent confidence interval, 0.51 to 0.98; P=0.04). This regimen was also associated with reductions in the relative risk of death related to the acquired immunodeficiency syndrome (0.73; 95 percent confidence interval, 0.51 to 1.04; P=0.09), progression to WHO stage 4 (0.50; 95 percent confidence interval, 0.28 to 0.90; P=0.02), or progression to stage 3 or higher (0.72; 95 percent confidence interval, 0.58 to 0.90; P=0.003). Multivitamins also resulted in significantly higher CD4+ and CD8+ cell counts and significantly lower viral loads. The effects of receiving vitamin A alone were smaller and for the most part not significantly different from those produced by placebo. Adding vitamin A to the multivitamin regimen reduced the benefit with regard to some of the end points examined.

Conclusions

Multivitamin supplements delay the progression of HIV disease and provide an effective, low-cost means of delaying the initiation of antiretroviral therapy in HIV-infected women.

N Engl J Med 2004;351

23-32.