Multivitamins costing $15 per person per year significantly reduced the risk of HIV disease progression and death in HIV-positive pregnant women in Tanzania, according to a study published in the July 1st edition of the New England Journal of Medicine. The investigators conclude that multivitamins would be a cheap, simple, and effective means of delaying the need for antiretroviral therapy in HIV-positive pregnant women in resource limited settings.
An accompanying editorial praises the rigour of the investigators study, and although it calls for further studies into the benefits of multivitamins involving large populations it says that treatment programmes and doctors would be justified in offering multivitamins.
Although there have been recent efforts to expand access to antiretroviral drugs in resource limited settings, many individuals remain without anti-HIV treatment. Furthermore, the WHO 3 X 5 scheme will only provide anti-HIV therapy to patients with advanced HIV disease. Micronutrients have been proposed as a means of slowing HIV disease progression. Accordingly investigators from the US and Tanzania conducted a randomised placebo controlled trial to evaluate the effect of micronutrients on the risks of HIV disease progression and death.
A total of 1078 HIV-positive pregnant women were recruited in Dar es Salaam in Tanzania between 1995 and 1997. Follow-up was provided until August 2003.
The women were randomised into one of four treatment arms:
- vitamin A supplementation (consisting of 30mg of beta carotene plus 5000 IU of preformed vitamin A)
- multivitamins (including 20mg of vitamin B1 20 mg of vitamin B2, 25mg of vitamin B6, 100 mg of niacin, 50mug of vitamin B12, 500 mg or vitamin C, 30mg of vitamin E, and 0.8mg of folic acid)
- a combination of vitamin A and multivitamins
- a placebo
At monthly clinic visits the women had a physical examination and reported any physical symptoms to a study nurse. The stage of every woman’s HIV disease was assessed at each study visiting using the WHO classification system. At baseline, and then at six monthly intervals, the women had blood samples taken to monitor CD4 and CD8 cell count. A total of 300 women were randomly selected to have six-monthly HIV viral load tests.
Baseline characteristics were comparable across all four arms of the study. A total of 299 women progressed to WHO stage 4 or died of an AIDS-related cause during the course of the study. This included 24.7% of women who received multivitamins, 26.1% of women who received multivitamins plus vitamin A, 29% of women receiving vitamin A alone, and 31.1% of women who were randomised to receive a placebo.
Compared to women in the placebo group, the women randomised to receive multivitamins were significantly less likely to progress to WHO stage 4 HIV disease or die of AIDS related causes (p = 0.04). The benefits of vitamin A supplementation alone were “for the most part not significantly different from those produced by a placebo”, write the investigators.
Multivitamins also had other benefits. Compared to the placebo they reduced the relative risk of progressing to WHO stage 4 (p = 0.02), and the risk of progressing to WHO stage 3 or higher (p = 0.03). Multivitamins had their strongest effect in the first two years of their use, but beneficial effects continued after this.
Multivitamins also reduced symptoms of HIV disease including fatigue, rash, upper respiratory tract infections and oral and gastrointestinal manifestations of HIV. CD4 cell counts were higher by 48 cells/mm3 in women who received multivitamins compared to those receiving the placebo (p = 0.001).
The addition of vitamin A to multivitamins, however, reduced the benefit of multivitamins.
Furthermore no benefit was derived for vitamin A supplementation alone in slowing progression to WHO stage 4 HIV disease, or WHO stage 3 HIV disease or above.
”Multivitamin supplementation with vitamin B complex, vitamin C, and vitamin E significantly delayed the progression of HIV disease amongst HIV-infected women, as reflected by the relative risk of progression to WHO stage 4 or deaths from AIDS, as well as other measures of disease progression”, write the investigators.
The investigators also stress the other benefits of multivitamin supplementation including a reduction in the incidence of symptoms of HIV disease, and better immune function. Reduced viral replication was also observed in women taking multivitamins compared to women randomised to receive the placebo (p = 0.01). The investigators believe that this is because of the antioxidant properties of vitamins C and E.
Although the investigators stress that the benefits of multivitamin supplementation were modest compared to the effects of HAART they estimate that the 0.18 log in HIV viral load seen in the women receiving multivitamins would translate into “an increase in time to progression to AIDS or death of approximately 30%.”
”Our data suggest that multivitamins delay onset of disease progression and thus the time to the initiation of antiretroviral therapy”, conclude the investigators, who add, “introducing these supplements would preserve antiretroviral drugs for later stages of the disease, avert adverse events…and significantly reduce treatment related costs.” An annual supply of multivitamins used in this trial is $15 per person per year.
High rates of adherence, approximately 80% in each treatment arm, were recorded over 71 months of follow-up, suggesting that fears about poor adherence to antiretrovirals are likely to prove unfounded.
An accompanying editorial praises the credibility of the investigators’ data praising the “sound study design and methods, appropriate analyses, and compatibility with limited existing data.” Although the editorial’s authors call for a large trial to assess the benefits of multivitamins in delaying HIV disease progression before definite recommendations can be made regarding their use, “individual treatment programmes and clinicians would be justified in routinely prescribing nutritional support, since it may provide benefit and does no harm.”
The editorial also notes that multivitamins could be offered through home-based care programmes, which are often the first healthcare service to be alerted to signs of HIV infection. The authors of the editorial also highlight the importance of providing food as part of antiretroviral treatment programmes.
However, the editorial concludes that although interventions like vitamin supplementation may provide simple and important interventions, “the need for antiretroviral therapy in Africa is real and compelling. The international community must continue to expand its efforts to meet this need.”
Further information on this website
Vitamins and minerals - overview
Fawzi WW et al. A randomized trial of multivitamin supplements and HIV disease progression and mortality. New England Journal of Medicine, 351: 23-32, 2004.
Marston B et al. Multivitamins, nutrition, and antiretroviral therapy for HIV disease in Africa. New England Journal of Medicine, 351, 78-80, 2004.