AIDS TREATMENT NEWS #134, September 6, 1991
Denny Smith

The May, 1991 edition of AIDS Targeted Information Newsletter (ATIN) included a good review of such studies, authored by Neil M. H. Graham, M. B. B. S., M. D., M. P. H., of the School of Hygiene and Public Health at The Johns Hopkins University. Dr. Graham raises the possibility of using abnormal fluctuations of micronutrients as markers for charting HIV progression. He also briefly addresses AIDS-associated weight loss or wasting syndrome, which, like the deficiencies mentioned above, may not necessarily be caused by malabsorption or diarrhea, and which may in turn increase susceptibility to new opportunistic infections.

We spoke to Dr. Graham by telephone and asked if he could elaborate on a few points in his review. Some of the studies to which he referred could create some confusion, since their results were often inconclusive or even contradictory.

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DS: If HIV infection is associated with decreased serum [blood] zinc levels, would you describe this as both a symptom and a blood marker?

NG: It is understandable that zinc deficiency could be looked at as a possible cofactor, because there is no doubt that a severe zinc deficiency can adversely affect immune functions. But it is difficult to say whether this is a cause, or an effect, of HIV progression. Inflammatory and neoplastic [cancer] processes are already known to decrease serum zinc, and increase serum copper. When we compared baseline zinc levels in seronegative and seropositive patients, we found that zinc intake had no relationship to disease progression in the seropositives. But levels of zinc in the blood did relate to progression, even after adjusting for CD4 [T-helper cell] count. This would imply that falling zinc levels represent a marker and not a contributor in HIV progression. So loading up with supplemental zinc may not help. In fact, one test-tube study suggested that HIV may actually require zinc in order to replicate.

DS: What would that mean in clinical care -- would giving zinc to patients not be useful, or actually feed HIV?

NG: No one has done clinical trials to compare supplementation with no supplementation, so we can't say for certain one way or the other. In most people with HIV, zinc deficiency is not so serious that it would dramatically impair immune function, and thus warrant therapeutic supplementation. At this point we are simply likening it to a marker, such as neopterin or beta 2 microglobulin.

DS: How much of this is also true for vitamin B12 deficiency?

NG: That situation is a bit less equivocal. There are data showing that B12 injections may benefit some individuals with HIV-related neurological conditions, particularly neuropathies, dementia and demyelinating conditions. But none of the relevant studies have used very big numbers, or controlled trials. I think that trials of B12 supplementation are well worth pursuing.

DS: Several of our readers have told us that their neuropathy was improved by B12 injections. One person said that B6 also had this effect. I was interested in the connection you made in your review between neopterin and the metabolism of B vitamins.

NG: Yes. Two studies reported in The Lancet that folate metabolism seems to be altered by rising neopterin levels, particularly in children with HIV who have developed dementia.

DS: For years we have been hearing about possible connections between HIV progression and increased serum neopterin, but HIV clinicians haven't seemed to put much stock in it. Ostensibly this provides a fresh reason to look into neopterin as a marker or cofactor.

NG: I think that's right. It certainly needs further study. I think both neopterin and beta 2 microglobulin should be considered as potential markers for HIV progression, or for measuring a response to therapy, particularly for neurologists treating HIV.

DS: What would you say is useful for clinicians to look for in terms of nutritional deficiencies in HIV infection?

NG: I think I'd definitely look for B12 and folate. They both tend to drop relatively early on in HIV, they are deficiencies that are known to cause problems, and they are potentially reversible. Zinc could be useful as a marker for progression. Body mass and weight loss should definitely be monitored. From our studies in the Multicenter AIDS Cohort Study we have noted a mild weight loss well before the progression to AIDS, and if you're going to intervene nutritionally, maybe it's worth starting before the appearance of major symptoms.

DS: What are your thoughts on the value of beta carotene in immune function?

NG: Beta carotene and vitamin A are of a lot of interest generally in developing countries, for benefiting eye problems as well as acute respiratory infections and diarrheal infections. They play an important role in immune function, especially in regard to surfaces lined with epithelial cells, which of course include the sites of respiratory and diarrheal infections. Vitamin A pretty clearly reduces morbidity and perhaps even mortality in children who suffer from deficiencies.

DS: Is there a caution against people taking too much vitamin A, especially people who are having drug-induced liver problems, or histories of hepatitis?

NG: Oh yes, that could be very dangerous. Nutrition as a discipline has gotten a bad name, because to some people it means doing what their mother told them to do, or what the local health food store is promoting.

DS: Unfortunately, it's true. At least one vitamin store in San Francisco sells nutritional "consultations," during which some people have been told that they cannot be healthy as long as they take AZT.

NG: That's very dangerous, and it happens a lot, not just to people with HIV, but everyone with chronic diseases -- cancer, asthma, etc. Nutrition is very hard to study scientifically, but we should be doing it. As more and more opportunistic infections come under control, nutritional changes and weight loss will become increasingly apparent, and we'll have to deal with it in a reasonable manner.

DS: The increasing focus on nutrition is exciting, because it implies that people will be around long enough for it to matter.

NG: That's a good point. Slowly but surely we're getting on to the next stage, treating AIDS as a chronic disease.

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