Mysterious hormone forecasts AIDS onset.

Abnormally low levels of an obscure adrenal hormone appear to foreshadow a progression from asymptomatic infection to full-blown AIDS, according to an intriguing new study The finding, if confirmed, may offer another means of tracking the deterioration of people infected with HIV, the virus that causes AIDS. In addition, it has ignited hope that the hormone may actually help protect against HIV.

The hormone is dehydroepiandrosterone (DHEA), a steroid manufactured by the adrenal gland. It has no known function in healthy people, yet research suggests it might help protect against heart disease, cancer, viral infections and infirmities related to old age.

"It does everything," says one of DHEA's most enthusiastic proponents, William Regelson of the Medical College of Virginia in Richmond. His mouse studies have suggested that DHEA enhances the body's defense against viral infections. Regelson's work and other research prompted a California team to investigate the steroid's role in AIDS.

The AIDS study, led by Mark A. Jacobson of the University of California, San Francisco, involved HIV-infected men in the San Francisco Men's Health Study whose blood samples were drawn at regular intervals and frozen. Jacobson's team focused on 108 men who still had few or no disease symptoms two years after entering the study He and his colleagues analyzed blood samples taken at the two-year point, looking at DHEA levels and the number of CD4 T-lymphocytes - white blood cells used as a laboratory marker for the severity of infection (SN: 11/4/89, p.298). They also checked to see which of these men developed AIDS over the following three years.

In the November JOURNAL OF INFECTIOUS DISEASES, they report an "impressive" association between low blood levels of DHEA and progression to AIDS among a subset of the HIV-infected men: those with CD4 counts of 200 to 499 per microliter of blood. (Healthy people have a CD4 count of about 1,200; with full-blown AIDS, the count drops below 200.) Even after the researchers took into account other factors known to affect HIV's progress, such as zidovudine treatment, the statistical link between DHEA and disease progression remained significant, they say.

Compared with men in the subset who possessed normal DHEA levels, those with low levels faced double the risk of progressing to AIDS during the next three years, the team found.

The significance of that finding remains unclear, cautions Carl Merril of the National Institute of Mental Health, who in 1989 reported the observation that HIV-infected people had lower-than-normal DHEA levels. DHEA's function - both in sickness and in health - remains enigmatic, he says. Low DHEA could represent just another laboratory marker for worsening disease, an indicator "that things are going dreadfully wrong with the adrenal gland," Merril suggests.

On the other hand, DHEA might play an active role in fighting HIV, Jacobson speculates. He notes that preliminary studies by Michael McGrath of UCSF indicate that DHEA may inhibit HIV replication, at least in the test tube. That finding, along with Regelson's work, suggests that DHEA in abundant levels may help shield against HIV progression, Jacobson says.

To begin testing that theory, his team and Elan Pharmaceuticals have embarked on an early clinical trial involving experimental DHEA treatment of 23 HIV-infected men in San Francisco. The Ireland-based drug firm manufactures a synthetic form of DHEA.

For now, the new report's primary significance may lie in its challenge to AIDS researchers. "This is a lead," Jacobson says. Here's something that seems to influence the progression of HIV."