Before AIDS was named, in 1982, East Africans knew the devastating syndrome as Slim Disease because of how victims wasted away. The appellation proved prescient. As researchers uncovered a link between Africans' weakened immune systems and malnutrition, they wondered: Might multivitamins delay progression of the AIDS virus, HIV?
The answer is yes. According to a study released last year by researchers in Tanzania and the Harvard School of Public Health (HSPH), a daily dose of vitamins C, E, and B- complex can slow the advance of HIV infection--and postpone the need for antiretroviral therapy (ART).
Multivitamins aren't meant to replace ART, the researchers stress. "ART is the gold standard for treating HIV/AIDS," explains Wafaie Fawzi, an associate professor of nutrition and epidemiology at HSPH and lead author of the New England Journal of Medicine (NEJM) study. "But at relatively low cost, multivitamins can prolong the time people can live and work before they require drugs--which for millions are not yet affordable, or even accessible."
Within eight months, funding was secured from the U.S. National Institute of Child Health and Human Development for an investigation in Tanzania into vitamins and health. A core team gathered that included Fawzi, Hunter, HSPH statistician Donna Spiegelman, and researchers Gernard Msamanga and Ernest Urassa of Muhimbili University in Tanzania, with Kapiga and others collaborating.
The idea of using vitamins to forestall AIDS isn't new. In the early 1990s, the U.S.-based Multi- center AIDS Cohort Study (MACS) found an association between an elevated intake of B vitamins, especially niacin, and a slowing of HIV disease progression in gay and bisexual American men. MACS investigators included Walter Willett, now chair of the Department of Nutrition at HSPH.
"No one knew whether these results would also hold true for developing countries, particularly in Africa, where the profile of the HIV/AIDS epidemic is very different from that in the United States," Willett says. That's because one HIV subtype predominates in the U.S., whereas numerous strains pervade Africa, he explains. Findings in gay and bisexual U.S. men could not be readily extrapolated to African populations. Moreover, it wasn't clear whether useful comparisons could be drawn between HIV's progression in relatively undernourished Africans and generally well-fed Americans.
After MACS came more vitamin studies led by researchers elsewhere. A 1999 observational study suggested that vitamin-B-complex supplements improved the health of black, HIV-infected South Africans. In 2003, researchers reported that multivitamins were associated with decreased mortality among HIV-infected Thai patients.
Yet no controlled trial of vitamin supplementation has involved as many HIV-infected people, or run for as long, as that launched in 1995 by Fawzi and colleagues. Spanning eight years, their trial enrolled nearly 1,100 HIV-infected pregnant women in Tanzania.
in a bottle
The researchers followed trial participants for nearly six years on average. Participants--who received standard care, including preventive interventions and treatment for opportunistic infections--were randomly assigned to one of four daily regimens:
The results were clear: Women who took vitamins C, E, and B-complex were 29 percent less likely to die during the study, or to progress to AIDS, than those on placebo. They were also less likely to suffer from mouth ulcers, diarrhea, fatigue, respiratory infections, and other symptoms. And they had higher numbers of key immune cells in their bloodstreams. The results built on another extraordinary benefit the researchers published in the Lancet in 1998: pregnant women who received vitamin C, E, and B-complex supplementation reduced the risks of fetal death, low birth weight, and severe prematurity by about 40 percent.
The Data Safety and Monitoring Board, an independent group of scientists who review trial results periodically, recommended a halt to the use of vitamin A in 2000 after Fawzi and colleagues linked it to a heightened risk of HIV transmission from mother to child, a surprising result given that research had shown vitamin A to decrease mortality rates among HIV-infected Tanzanian children. The finding of increased transmission, confirmed by other studies, highlights the importance of investigating interventions presumed to be beneficial, Fawzi notes. Adding vitamin A to the multivitamin mix also appeared to diminish the regimen's ability to slow HIV disease progression.
No one knows how multivitamins slow HIV's advance. Some studies hint that vitamins enhance immune defenses; they may also strengthen the bonds between cells that line the mouth and the gastrointestinal tract, prime points of entry for opportunistic infections. Multivitamins may also protect cells from oxidative stress, the same chemical process that turns iron to rust.
Andrew Tomkins of the Institute of Child Health in London, who serves with Fawzi on an advisory group that helps WHO set its nutrition and HIV/AIDS agenda, calls the Tanzanian study "extremely promising."
"From a policy perspective, this study suggests that micronutrients could be given in the routine management of people with HIV in developing countries," Tomkins says. "However, the study took place in one city, in one country. The results would need to be replicated for other African countries, as well as for parts of Asia."
ART can cost upwards of $300 to $1,200 per person annually, according to WHO. Programs have stepped up efforts to make ART accessible. WHO's 3 by 5 Initiative aims to get ART to three million people in developing and middle-income countries by the close of 2005 (although the agency announced in June that it may fall short of that goal). HSPH, too, has a role: The School is working with officials to expand access in Tanzania, Botswana, and Nigeria, sites of longstanding collaborations. In 2004, HSPH received funding from the Bush Administration's President's Emergency Plan for AIDS Relief, or PEPFAR. HSPH Professor of Immunogy and Infectious Diseases Phyllis Kanki is the principal investigator on the five-year grant, estimated at $100 million, which aims to make drugs available to 75,000 people and to spearhead new research. As director of PEPFAR's Tanzania component, Fawzi is collaborating with partners at HSPH, Muhimbili University, the Dar es Salaam City Council, and the Ministry of Health to expand ART's availability.
Meanwhile, Fawzi and David Hunter have been quick to stymie attempts to equate multivitamins with ART. In May, the researchers issued a statement condemning advertisements placed in U.S. and South African newspapers by businessman Matthias Rath, whose company sells vitamins. Rath had erroneously pointed to HSPH's study as support for his claim that vitamins are superior to ART for treating HIV/AIDS.
Emphasizes Fawzi: "People advanced enough in their disease to warrant ART should have antiretroviral drugs." But time is running out, he says.
"By the end of 2003, fewer than eight percent of the six million people eligible for ART worldwide were receiving it," Fawzi laments. "We hope multivitamins will help prolong and improve the quality of many lives until ART is recommended--and made available."
Christina Roache edits Harvard Public Health NOW, the School's biweekly newsletter, available at www.hsph.harvard.edu/now.
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