Selenium supplementation has positive effect on HIV viral load, CD4 counts in randomised study

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Daily supplementation with 200μg of selenium daily stabilised viral load and modestly increased CD4 cell counts in both untreated and viremic patients on antiretroviral therapy in a nine-month randomised trial, researchers from the University of Miami report in the January 22ndArchives of Internal Medicine. They say their findings suggest a role for selenium supplementation as a simple, inexpensive and safe adjunct therapy for HIV disease, and that longer-term research into its use should be undertaken.

Selenium is a mineral essential for human health. Deficiencies can lead to immune dysfunction and cardiomyopathy, and are common in resource-limited settings and in countries with low selenium levels in soil.

Selenium deficiency has been noted in HIV disease and predicts an increased risk of death. However, incubation of HIV-infected monocytes in the test tube with selenium results in the suppression of HIV replication.

Glossary

placebo

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

detectable viral load

When viral load is detectable, this indicates that HIV is replicating in the body. If the person is taking HIV treatment but their viral load is detectable, the treatment is not working properly. There may still be a risk of HIV transmission to sexual partners.

replication

The process of viral multiplication or reproduction. Viruses cannot replicate without the machinery and metabolism of cells (human cells, in the case of HIV), which is why viruses infect cells.

intent to treat analysis

All participants in a clinical trial are included in the final analysis, in the groups they were originally assigned to, whether or not they actually completed their course of treatment. This method provides a better estimate of the real-world effect of a treatment than an ‘on treatment’ analysis.

plasma

The fluid portion of the blood.

Researchers from the University of Miami, who have extensive experience of investigating the relationship between HIV disease and micronutrient deficiencies, recruited 262 adult HIV-positive patients between 2001 and 2005, three quarters of whom were receiving antiretroviral therapy on entry into the study.

Participants were randomised to receive 200μg of selenium daily in the form of selenium yeast capsules (Selenomax), or a placebo. Selenomax was chosen because it was considered most likely to provide high levels of bioavailable selenium - not all selenium supplements may be as effective in raising plasma selenium levels.

One hundred and forty-one were randomised to receive selenium and 121 to receive placebo. Adherence was monitored by a computerised chip in the cap of the pill bottle.

Viral load, CD4 cell count, plasma selenium levels and metabolic parameters were monitored at baseline, at nine months and after 18 months.

At baseline there were no significant differences in the characteristics of the two treatment groups. Selenium levels were similar in the two groups.

Selenium group

Placebo group

Mean viral load (copies/ml)

24,558 (+/- 87,051)

10,491 (+/- 20,251)

Median viral load
(copies/ml)

688

209

Median CD4 cell count

417

440

%Antiretroviral therapy

74.6%

71.7%

% undetectable viral load

37.6%

35.5%

Prior AIDS diagnosis

62.7%

60%

Mean selenium level (μg/L)

112

110

After nine months 174 participants remained in the study (91 selenium group, 83 placebo group), with a comparable rate of loss to follow-up or study withdrawal in the two arms.

Mean selenium levels rose by 0.5μg/l in the placebo group and by 323.2 μg/l in the selenium group (p26.1μg/l).

By an intent to treat analysis which controlled for baseline CD4 count and viral load as well as demographic factors including disease stage, prior drug use and antiretroviral regimen, a greater increase in selenium concentration was shown to predict decreased viral load (p

Non-responders in the selenium group had an average viral load increase of +0.29 log10 copies/ml, while selenium responders had no significant change in viral load.

Non-responders in the selenium group had an average CD4 cell decrease of 25 cells/mm3, while responders had an average CD4 cell increase of 27 cells/mm3.

Both viral load and CD4 cell count changes in the selenium non-responders group were of similar magnitude to those seen in the placebo group.

Around half of those receiving antiretroviral therapy in this study had detectable viral load at baseline, and those with detectable viral load in the placebo group experienced a twofold greater increase in viral load than those in the selenium group. This finding led the authors to conclude that the selenium effect on viral load was independent of any effect of antiretroviral therapy.

However the authors say it is not possible to explain why selenium supplementation appears to have a suppressive effect on viral load. Selenium may reduce the oxidative stress that is one stimulant of HIV replication, or it may directly suppress HIV replication, but the authors say that strong evidence for the latter is still lacking.

The authors note that the main limitation of their study is the limited follow-up. They have data on nine months follow-up at present, and have only measured selenium levels, viral load and CD4 cell counts at one time point after starting selenium supplementation. They recommend further research to examine how selenium exerts an effect on viral load, and to determine whether the effect of supplementation on the CD4 cell count is solely a consequence of viral load suppression, or whether selenium also has an additional immunological benefit in HIV disease.

References

Hurwitz BE et al. Suppression of human immunodeficiency virus type 1 viral load with selenium. A randomised controlled trial. Arch Int Med 167: 148-154, 2007.