A Randomized Trial of Multivitamin Supplements and HIV Disease Progression and Mortality
Wafaie W. Fawzi, M.B., B.S., Dr.P.H., Gernard I. Msamanga, M.D., Sc.D., Donna Spiegelman, Sc.D., Ruilan Wei, Ph.D., Saidi Kapiga, M.D., Sc.D., Eduardo Villamor, M.D., Dr.P.H., Davis Mwakagile, M.D., M.Med., Ferdinand Mugusi, M.D., M.Med., Ellen Hertzmark, M.A., Max Essex, D.V.M., Ph.D., and David J. Hunter, M.B., B.S., Sc.D.
Background Results from observational studies suggest that micronutrientstatus is a determinant of the progression of human immunodeficiencyvirus (HIV) disease.
Methods We enrolled 1078 pregnant women infected with HIV ina double-blind, placebo-controlled trial in Dar es Salaam, Tanzania,to examine the effects of daily supplements of vitamin A (preformedvitamin A and beta carotene), multivitamins (vitamins B, C,and E), or both on progression of HIV disease, using survivalmodels. The median follow-up with respect to survival was 71months (interquartile range, 46 to 80).
Results Of 271 women who received multivitamins, 67 had progressionto World Health Organization (WHO) stage 4 disease or died the primary outcome as compared with 83 of 267 womenwho received placebo (24.7 percent vs. 31.1 percent; relativerisk, 0.71; 95 percent confidence interval, 0.51 to 0.98; P=0.04).This regimen was also associated with reductions in the relativerisk 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). Multivitaminsalso resulted in significantly higher CD4+ and CD8+ cell countsand significantly lower viral loads. The effects of receivingvitamin A alone were smaller and for the most part not significantlydifferent from those produced by placebo. Adding vitamin A tothe multivitamin regimen reduced the benefit with regard tosome of the end points examined.
Conclusions Multivitamin supplements delay the progression ofHIV disease and provide an effective, low-cost means of delayingthe initiation of antiretroviral therapy in HIV-infected women.
Source Information
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 mina{at}hsph.harvard.edu.
Allen, L. H., Peerson, J. M., Olney, D. K.
(2009). Provision of Multiple Rather Than Two or Fewer Micronutrients More Effectively Improves Growth and Other Outcomes in Micronutrient-Deficient Children and Adults. J. Nutr.
139: 1022-1030
[Abstract][Full Text]
Meyer, M. S., Applebaum, K. M., Furniss, C. S., Peters, E. S., Luckett, B. G., Smith, J. F., Bryan, J., McClean, M. D., Marsit, C., Kelsey, K. T.
(2008). Human Papillomavirus-16 Modifies the Association between Fruit Consumption and Head and Neck Squamous Cell Carcinoma. Cancer Epidemiol. Biomarkers Prev.
17: 3419-3426
[Abstract][Full Text]
Hamel, M. J., Greene, C., Chiller, T., Ouma, P., Polyak, C., Otieno, K., Williamson, J., Shi, Y. P., Feikin, D. R., Marston, B., Brooks, J. T., Poe, A., Zhou, Z., Ochieng, B., Mintz, E., Slutsker, L.
(2008). Does Cotrimoxazole Prophylaxis for the Prevention of HIV-Associated Opportunistic Infections Select for Resistant Pathogens in Kenyan Adults?. Am J Trop Med Hyg
79: 320-330
[Abstract][Full Text]
Gan, R., Eintracht, S., Hoffer, L. J.
(2008). Vitamin C Deficiency in a University Teaching Hospital. J. Am. Coll. Nutr.
27: 428-433
[Abstract][Full Text]
Villamor, E., Koulinska, I. N, Furtado, J., Baylin, A., Aboud, S., Manji, K., Campos, H., Fawzi, W. W
(2007). Long-chain n 6 polyunsaturated fatty acids in breast milk decrease the risk of HIV transmission through breastfeeding. Am. J. Clin. Nutr.
86: 682-689
[Abstract][Full Text]
VILLAMOR, E., MSAMANGA, G., SAATHOFF, E., FATAKI, M., MANJI, K., FAWZI, W. W.
(2007). EFFECTS OF MATERNAL VITAMIN SUPPLEMENTS ON MALARIA IN CHILDREN BORN TO HIV-INFECTED WOMEN. Am J Trop Med Hyg
76: 1066-1071
[Abstract][Full Text]
Tohill, B. C, Heilig, C. M, Klein, R. S, Rompalo, A., Cu-Uvin, S., Piwoz, E. G, Jamieson, D. J, Duerr, A.
(2007). Nutritional biomarkers associated with gynecological conditions among US women with or at risk of HIV infection. Am. J. Clin. Nutr.
85: 1327-1334
[Abstract][Full Text]
Fawzi, W. W, Msamanga, G. I, Kupka, R., Spiegelman, D., Villamor, E., Mugusi, F., Wei, R., Hunter, D.
(2007). Multivitamin supplementation improves hematologic status in HIV-infected women and their children in Tanzania. Am. J. Clin. Nutr.
85: 1335-1343
[Abstract][Full Text]
Drain, P. K, Kupka, R., Mugusi, F., Fawzi, W. W
(2007). Micronutrients in HIV-positive persons receiving highly active antiretroviral therapy. Am. J. Clin. Nutr.
85: 333-345
[Abstract][Full Text]
Hurwitz, B. E., Klaus, J. R., Llabre, M. M., Gonzalez, A., Lawrence, P. J., Maher, K. J., Greeson, J. M., Baum, M. K., Shor-Posner, G., Skyler, J. S., Schneiderman, N.
(2007). Suppression of Human Immunodeficiency Virus Type 1 Viral Load With Selenium Supplementation: A Randomized Controlled Trial. Arch Intern Med
167: 148-154
[Abstract][Full Text]
Kuhn, L., Coutsoudis, A., Trabattoni, D., Archary, D., Rossi, T., Segat, L., Clerici, M., Crovella, S.
(2006). Synergy between mannose-binding lectin gene polymorphisms and supplementation with vitamin A influences susceptibility to HIV infection in infants born to HIV-positive mothers.. Am. J. Clin. Nutr.
84: 610-615
[Abstract][Full Text]
Shenkin, A
(2006). Micronutrients in health and disease.. Postgrad. Med. J.
82: 559-567
[Abstract][Full Text]
Stringer, J. S. A., Zulu, I., Levy, J., Stringer, E. M., Mwango, A., Chi, B. H., Mtonga, V., Reid, S., Cantrell, R. A., Bulterys, M., Saag, M. S., Marlink, R. G., Mwinga, A., Ellerbrock, T. V., Sinkala, M.
(2006). Rapid scale-up of antiretroviral therapy at primary care sites in Zambia: feasibility and early outcomes.. JAMA
296: 782-793
[Abstract][Full Text]
Stephensen, C. B, Marquis, G. S, Jacob, R. A, Kruzich, L. A, Douglas, S. D, Wilson, C. M
(2006). Vitamins C and E in adolescents and young adults with HIV infection.. Am. J. Clin. Nutr.
83: 870-879
[Abstract][Full Text]
Van Rie, A., Madhi, S. A., Heera, J. R., Meddows-Taylor, S., Wendelboe, A. M., Anthony, F., Violari, A., Tiemessen, C. T.
(2006). Gamma Interferon Production in Response to Mycobacterium bovis BCG and Mycobacterium tuberculosis Antigens in Infants Born to Human Immunodeficiency Virus-Infected Mothers. CVI
13: 246-252
[Abstract][Full Text]
McGrath, N., Bellinger, D., Robins, J., Msamanga, G. I., Tronick, E., Fawzi, W. W.
(2006). Effect of Maternal Multivitamin Supplementation on the Mental and Psychomotor Development of Children Who Are Born to HIV-1-Infected Mothers in Tanzania. Pediatrics
117: e216-e225
[Abstract][Full Text]
Severe, P., Leger, P., Charles, M., Noel, F., Bonhomme, G., Bois, G., George, E., Kenel-Pierre, S., Wright, P. F., Gulick, R., Johnson, W. D. Jr., Pape, J. W., Fitzgerald, D. W.
(2005). Antiretroviral therapy in a thousand patients with AIDS in Haiti.. NEJM
353: 2325-2334
[Abstract][Full Text]
Witte, K. K.A., Nikitin, N. P., Parker, A. C., von Haehling, S., Volk, H.-D., Anker, S. D., Clark, A. L., Cleland, J. G.F.
(2005). The effect of micronutrient supplementation on quality-of-life and left ventricular function in elderly patients with chronic heart failure. Eur Heart J
26: 2238-2244
[Abstract][Full Text]
Villamor, E., Saathoff, E., Manji, K., Msamanga, G., Hunter, D. J, Fawzi, W. W
(2005). Vitamin supplements, socioeconomic status, and morbidity events as predictors of wasting in HIV-infected women from Tanzania. Am. J. Clin. Nutr.
82: 857-865
[Abstract][Full Text]
Chisenga, M., Kasonka, L., Makasa, M., Sinkala, M., Chintu, C., Kaseba, C., Kasolo, F., Tomkins, A., Murray, S., Filteau, S.
(2005). Factors Affecting the Duration of Exclusive Breastfeeding Among HIV-Infected and -Uninfected Women in Lusaka, Zambia. J Hum Lact
21: 266-275
[Abstract]
Villamor, E., Fawzi, W. W.
(2005). Effects of Vitamin A Supplementation on Immune Responses and Correlation with Clinical Outcomes. Clin. Microbiol. Rev.
18: 446-464
[Abstract][Full Text]
Merchant, A. T., Msamanga, G., Villamor, E., Saathoff, E., O'Brien, M., Hertzmark, E., Hunter, D. J., Fawzi, W. W.
(2005). Multivitamin Supplementation of HIV-Positive Women during Pregnancy Reduces Hypertension. J. Nutr.
135: 1776-1781
[Abstract][Full Text]
Darnton-Hill, I., Webb, P., Harvey, P. W., Hunt, J. M, Dalmiya, N., Chopra, M., Ball, M. J, Bloem, M. W, de Benoist, B.
(2005). Micronutrient deficiencies and gender: social and economic costs. Am. J. Clin. Nutr.
81: 1198S-1205S
[Abstract][Full Text]
Villamor, E., Saathoff, E., Bosch, R. J, Hertzmark, E., Baylin, A., Manji, K., Msamanga, G., Hunter, D. J, Fawzi, W. W
(2005). Vitamin supplementation of HIV-infected women improves postnatal child growth. Am. J. Clin. Nutr.
81: 880-888
[Abstract][Full Text]
Piwoz, E. G., Bentley, M. E.
(2005). Women's Voices, Women's Choices: The Challenge of Nutrition and HIV/AIDS. J. Nutr.
135: 933-937
[Abstract][Full Text]
Fawzi, W., Msamanga, G., Spiegelman, D., Hunter, D. J.
(2005). Studies of Vitamins and Minerals and HIV Transmission and Disease Progression. J. Nutr.
135: 938-944
[Abstract][Full Text]
Villamor, E., Misegades, L., Fataki, M. R, Mbise, R. L, Fawzi, W. W
(2005). Child mortality in relation to HIV infection, nutritional status, and socio-economic background. Int J Epidemiol
34: 61-68
[Abstract][Full Text]
Ambrus, J. L. Sr., Ambrus, J. L. Jr.
(2004). Nutrition and Acquired Immunodeficiency Syndrome. Exp. Biol. Med.
229: 865-865
[Full Text]
Schroecksnadel, K., Zangerle, R., Fuchs, D., Fawzi, W. W., Msamanga, G. I., Hunter, D. J.
(2004). Multivitamin Supplements and HIV Disease Progression. NEJM
351: 1353-1354
[Full Text]
(2004). A Vitamin a Day to Keep HIV at Bay. JWatch Infect. Diseases
2004: 2-2
[Full Text]
(2004). Vitamins to Treat HIV? Only in Africa, Perhaps. JWatch General
2004: 6-6
[Full Text]
Marston, B., De Cock, K. M.
(2004). Multivitamins, Nutrition, and Antiretroviral Therapy for HIV Disease in Africa. NEJM
351: 78-80
[Full Text]