Cheap multivitamin pill increases survival in those with low CD4 counts

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A multivitamin and mineral supplement with a local cost of about 60p a month has been found to enhance survival of HIV-positive people with less than 200 CD4 cells unable to access HAART, according to a Thai study published in the latest issue of the journal, AIDS.

The Thai study is the first ever double-blind placebo-controlled randomised trial to assess the clinical significance of vitamins and minerals in people with HIV, and offers some small comfort to those people living in countries where access to HAART is limited or non-existent.

The study was undertaken by a multinational team spearheaded by the Department of Infectious and Tropical Diseases at the London School of Hygiene and Tropical Medicine in co-operation with the Thai Ministry of Public Health.

Glossary

placebo

A pill or liquid which looks and tastes exactly like a real drug, but contains no active substance.

p-value

The result of a statistical test which tells us whether the results of a study are likely to be due to chance and would not be confirmed if the study was repeated. All p-values are between 0 and 1; the most reliable studies have p-values very close to 0. A p-value of 0.001 means that there is a 1 in 1000 probability that the results are due to chance and do not reflect a real difference. A p-value of 0.05 means there is a 1 in 20 probability that the results are due to chance. When a p-value is 0.05 or below, the result is considered to be ‘statistically significant’. Confidence intervals give similar information to p-values but are easier to interpret. 

plasma

The fluid portion of the blood.

surrogate marker

An indirect indicator of something, such as measuring viral load to assess the treatment effect of a drug.

 

hazard ratio

Comparing one group with another, expresses differences in the risk of something happening. A hazard ratio above 1 means the risk is higher in the group of interest; a hazard ratio below 1 means the risk is lower. Similar to ‘relative risk’.

Just under 500 people with CD4 counts between 50 and 550 cells/mm3 were enrolled in the trial at Siriraj Hospital, Bangkok between March 2000 and January 2001. 242 were randomly assigned to the supplement arm and 239 to the placebo arm. Neither doctor nor patient knew which pills they were receiving, since both supplements and placebo were prepared to look exactly the same. The pills were taken twice a day after food.

The total daily vitamin/mineral doses contained within the pills were:

  • Vitamin A 3000 µg
  • Beta-carotene 6 mg
  • Vitamin D3 20 µg
  • Vitamin E 80 mg
  • Vitamin K 180 µg
  • Vitamin C 400 mg
  • Vitamin B1 24 mg
  • Vitamin B2 15 mg
  • Vitamin B6 40 mg
  • Vitamin B12 30 µg
  • Folacin 100 µg
  • Pantothenic acid 40 mg
  • Iron 10 mg
  • Magnesium 200 mg
  • Manganese 8 mg
  • Zinc 30 mg
  • Iodine 300 µg
  • Copper 3 mg
  • Selenium 400 µg
  • Chromium 150 µg
  • Cystine 66 mg

 

CD4 counts were taken at baseline from all participants, and the first consecutive 140 (71 in active and 69 in placebo arm) participants also had measurements of plasma viral load and vitamin E and selenium levels.

At the end of 48 weeks, 23 (5%) had died and 379 (79%) were known to have survived. The rest were lost to follow-up. Eight deaths occurred in the supplement and 15 in the placebo arm. The mortality rate was significantly lower in the supplement arm in those who began the study with CD4 counts below 200 cells/mm3. For those with CD4 counts between 101-200 cells/mm3 the mortality hazard ratio was 0.37; 95% CI 0.13-1.06; p=0.052, and for those with CD4 counts below 100 cells/mm3 the mortality hazard ratio was 0.26; 95% CI 0.07-0.97; p=0.03.

No impact was seen, however, on hospital admissions, CD4 cell count or plasma viral load, which, say the study’s authors “highlights the need to measure impact against clinical endpoints rather than on surrogate markers, as the beneficial effects would have been missed if only surrogate markers had been measured.”

Whether the same supplements would make a difference to survival in countries where macronutrient malnutrition is endemic - in particular, sub-Saharan Africa - is difficult to ascertain given that all previous studies on micronutrient supplementation have taken place in well-fed populations.

This week an editorial by Professor JP van Niekerk in the South African Medical Journal criticises a diet rich in many of the micronutrients studied in Thailand that is being touted by South Africa’s Health Minister, Manto Tshabalala-Msimang Manto, as a way to improve HIV survival. "We should eat garlic because of its antibacterial and anti-fungal properties, lemon because of Vitamin C and olive oil as a source of Vitamin A and E," she told an audience in Gauteng in August this year. "All these vitamins are good antioxidants and they are good for everybody."

But Tshabalala-Msimang's is being criticised less for her lemon, garlic and olive oil diet - although these ingredients have not been proven to impact HIV disease progression - more because they were suggested as an alternative to the S.A. government providing antiretrovirals to their people many of whom cannot always afford basics like bread and clean water. "When the poor purchase the product, its price limits the purchase of other wholesome foods, which in turn is likely to adversely affect (the poor's) nutritional status," writes Professor van Niekerk.

Nevertheless the authors of the Thai study strongly suggest that a trial of multivitamin-mineral supplements begin urgently in Africa “because if micronutrient supplementation can provide a small amount of benefit and defer the initiation of highly active antiretroviral therapy, this could have high public health importance in Africa.”

Further information on this website

Nutrition - booklet in the award winning information for HIV-positive people series (pdf)

Vitamins and minerals - overview

High doses of vitamin C lower indinavir levels - news story

References

Jiamton et al. A randomized trial of the impact of multiple micronutrient supplementation on mortality among HIV-infected individuals living in Bangkok AIDS 17:2461-2469, 2003.