A randomized trial of multivitamin supplements and HIV disease progression and mortality

N Engl J Med. 2004 Jul 1;351(1):23-32. 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.

Publication types

  • Clinical Trial
  • Randomized Controlled Trial
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • AIDS-Related Opportunistic Infections / prevention & control
  • Adult
  • CD4 Lymphocyte Count
  • Dietary Supplements*
  • Disease Progression
  • Female
  • HIV Infections / drug therapy*
  • HIV Infections / immunology
  • HIV Infections / mortality
  • HIV Infections / transmission
  • Humans
  • Infectious Disease Transmission, Vertical
  • Micronutrients / adverse effects
  • Micronutrients / therapeutic use*
  • Pregnancy
  • Pregnancy Complications, Infectious / drug therapy
  • Tanzania / epidemiology
  • Viral Load
  • Vitamin A / adverse effects*
  • Vitamin A / pharmacology
  • Vitamin A / therapeutic use
  • Vitamins / adverse effects
  • Vitamins / pharmacology
  • Vitamins / therapeutic use*


  • Micronutrients
  • Vitamins
  • Vitamin A