In addition to food, people with HIV may need additional micronutrients. The same cycle of malnutrition and infection (see figure 1) that occurs with macronutrients is seen with micronutrients as well. People with serious infections or diseases, may have altered intake, absorption and metabolism of various micronutrients. These deficiencies in turn can weaken the immune system and increase the risk of infection.
Micronutrient supplementation can improve health — for example, vitamin A supplementation reduces mortality from a variety of causes in children under 5. Moreover, vitamin and minerals can be relatively easy and inexpensive to administer — but they should not be seen as a magic bullet.
In fact, the effects of micronutrient deficiencies and/or supplementation on HIV disease are complex according to Professor Henrik Friis of the Institute of Public Health Science at the University of Copenhagen, Denmark. He told the audience at the WHO meeting of a variety of methodological problems that make designing or deciphering vitamin and mineral studies difficult.
HIV infection increases a person’s requirements for a number of micronutrients, “but,” said Dr. Friis “the magnitude of the effect of HIV on micronutrient status or requirements depends on 1) the micronutrient in question, 2) the stage of HIV infection — it is clear that the effect increases as the patient becomes more symptomatic — and 3) the [patient’s] access to care and treatment of the common opportunistic infections and HIV”.
There is clear evidence that micronutrient status affects both susceptibility to and progression of HIV infection as well as general health, pregnancy outcomes, growth in children, etc. Micronutrients also interact with drug therapy, affecting the bioavailability, effectiveness, and/or safety or medicines.
In severe cases, micronutrient deficiency leads to a complex known as NAIDS or nutritionally acquired immunodeficiency syndrome — which, like AIDS, increases susceptibility to secondary infections. In a person with HIV, NAIDS may contribute to CD4 cell decline and increase the risk of progression to AIDS and death. In addition, poor micronutrient status also leads to oxidative stress, which has been directly shown to increase HIV replication — potentially speeding progression.
Much of the data on micronutrients and HIV and AIDS has been based on observational studies — but their findings are not always reliable. For one thing, it is difficult to assess micronutrient intake in these studies. “People don’t remember what they have been eating and they report it inaccurately,” said Friis. In addition, it is difficult to study just one micronutrient on its own because bioavailability may depend on intake of other nutrients. Also, biomarkers used to measure nutrient status in the blood are not always trustworthy when there is an infection in the patient.
As a result, there’s a potential for “bias and confounding that leads to spurious associations,” said Dr. Friis. As an example, he noted a vitamin study in Malawi a decade ago that caused considerable concern when it suggested that low serum retinal (a biomarker for vitamin A) was association with a higher rate of mother to child transmission (MTCT). This lead to a number of vitamin A supplementation studies that failed to show any positive affect on MTCT see below). Dr. Friis said there were a number of other possible explanations for the Malawi findings.
“We cannot base our recommendations on observational data,” said Dr. Friis. “Recommendations have to be based on randomised controlled trials that show cause and effect.” But there are some limitations even for randomised controlled trials when investigating the role of micronutrients in HIV and AIDS. For example:
The effects of the intervention depends on background intake
- especially likely in those with low intake
The intervention may not be effective at fixing the deficiency
Micronutrient deficiencies co-exist
- the typical cereal-based diet consumed in resource-limited settings is low in several micronutrients
- infections increase requirement of several micronutrients
Micronutrients interact,for example:
- Intake of one reduces absorption of another: zinc-iron
- Intake of one increases excretion of another: zinc-copper
- Deficiency of one impairs metabolism of another:
- Copper deficiency leads to iron deficiency anaemia
- Zinc deficiency leads to vitamin A deficiency
- High intake of one changes requirements of another
- Vitamin C reduces requirements of vitamin E
- Vitamin C increases absorption of iron
- Iron may increase requirement of C, but make it harmful
- Micronutrients interact with other factors
As a result, data from several RCT may be needed before making any recommendations for micronutrient supplementation.
Dr. Friis reviewed what has been published on the interaction between HIV disease and iron, selenium and zinc.
Zinc is essential for growth and synthesis of lean body mass and for a healthy immune system. However, if the given dose of zinc is too high, it can be immunosuppressive.
In children, zinc supplementation of children reduces complications from diarrhoea, pneumonia and malaria. In people with HIV, it should theoretically be beneficial.
Then data from the Multicenter AIDS Cohort Study (MACS) in the US suggested that zinc intake 30% above RDA is associated with a higher rate of HIV progression and death. But levels of zinc in the American diet are very high so the MACS data are not really generalisable to populations with low intake of zinc, such as in Africa.
More research needs to be conducted in settings where there zinc deficiency and HIV prevalence is common to determine the optimum required daily allowance (RDA), and the dose needed to improve HIV and non-HIV outcomes.
There was a small study in Zambia in which 106 HIV+ adults with persistent diarrhoea received 200 mg of zinc and other micronutrients for 2 weeks. It found no effect on morbidity over 12 weeks.
More recently, a few South African studies have reported that zinc supplementation is safe in HIV-infected children and does not increase HIV viral load or reduce CD4 cell count.
In one placebo controlled study at GreysHospital zinc supplementation (zinc sulphate 10 mg /d) significantly reduced frequency of watery diarrhea, and there was a trend toward reduced frequency of pneumonia in children. The most recent RCT found a significant reduction in serious adverse events (hospitalizations) in children receiving zinc (3 mg/kg/day).