Selenium & HIV Infection

This article first appeared in the
March, 1995 issue of VRP's Nutritional News

A recent study published in the Journal of Medicinal Chemistry has presented provocative evidence that selenium plays a significant role in the life cycle of the Human Immunodeficiency Virus (HIV) and the development of AIDS. In this paper the authors present evidence for the existence of several previously unnoticed genes in HIV-1 that potentially encode for selenoproteins. Some of these genes are highly conserved among different varieties of HIV, as well as other viruses, and may play a pivotal role in the replication of HIV within infected cells. Their investigation provided tentative evidence for the existence of up to four selenoproteins in HIV-1, a remarkable finding in light of the fact that only five selenoproteins have been found in humans.

Based on the finding of genes that encode for selenoproteins, the authors expanded the role for selenium in HIV infection by presenting previously published documentation of a characteristic decline in plasma selenium levels in AIDS and AIDS-related complex (ARC), which has been assumed to be due to malabsorption. In light of their results, the authors suggest that although this decline in selenium status may be entirely due to malabsorption, it is possible that the symptoms of progressive selenium depletion in HIV infection are at least partially due to sequestration of selenium in viral selenoproteins. Regardless of the mechanism, however, it seems clear that selenium status is compromised in HIV-infected patients, and this leads to an impairment of many selenium-dependent enzymes. Among these impairments are a decrease in antioxidant defenses (glutathione peroxidase) and thyroid hormone metabolism (type I 5'-Deiodinase). Indeed, the researchers present documentation of significant decreases in the function of both these selenium-dependent enzyme systems, with red blood cell glutathione peroxidase levels being reduced almost fifty percent and thyroid hormone abnormalities (low T3 levels) being linked to metabolic depression and weight loss in AIDS patients. In two brief clinical trials, selenium supplementation was reported to lead to symptomatic improvements in AIDS patients, and more extensive clinical trials of selenium are currently underway in Germany. This is not surprising, as selenium status is not only compromised in AIDS patients, but the author's evidence suggests that the selenoproteins produced by HIV directly effect viral expression. In the words of the authors, "This suggests the hypothesis that the ultimate depletion of selenium within an infected cell could be a signal for unrestrained expression of viral genes and thus be a trigger for release from latency." Indeed, the authors hypothesize that one of these selenoprotein coding genes may be an activator/repressor protein that could potentially turn off HIV expression. Additionally, the authors found evidence of similar genes in a variety of other viruses, raising the possibility that selenium is involved in the expression and life cycle of other viruses. While this work is preliminary, and the significance of these selenoprotein coding genes have yet to be elucidated, there is little question about the importance of adequate selenium status in HIV infected patients. Evidence is mounting not only that selenium metabolism is altered during HIV infection, but that supplementation may be of benefit in countering this alteration in selenium utilization and the pathologies this causes.

The authors propose that according to the literature, long-term supplementation with 200 micrograms a day of selenium is considered safe, although signs of selenium toxicity begin to appear after prolonged intake of 1000+ micrograms a day. Incidentally, vitamin E has been shown to lower the toxicity and increase the antioxidant effectiveness of selenium, and should preferably be taken on a daily basis with selenium. A reasonable recommendation would be approximately 300-600 i.u. of vitamin E and 200- 300 micrograms of selenium daily. The selenate form of selenium is preferred because of its stability to reduction into low-bioavailability elemental selenium (by reducing agents like vitamin C) and its high biopotency in restoring selenium status. Hopefully, long-term clinical trials of selenium supplements in HIV patients will help to determine the optimal dosage of selenium for the maintenance of adequate selenium status in HIV-infected persons, as well as the impact this has on the progression of the disease.

Reference:
E.W. Taylor, C.S. Ramanathan, R.K. Jalluri, et al, J Med Chem 1994; 37: 2637-2654.