One of the most puzzling riddles for clinicians who treat people with HIV infection to unravel is why individuals vary so much in the rate at which their infection progresses to full-blown AIDS. Results from a seven-year prospective study suggest that a confluence of psychosocial and neuroendocrine factors may play a significant role in hastening the time between acquiring HIV and developing AIDS.

It appears that a combination of stressful life events, a perceived lack of social supports, the use of denial as a coping mechanism, depressive symptoms, and higher cortisol levels accelerate the progression of HIV infection to AIDS.

Data supporting this confluence of factors come from a study by Jane Leserman, Ph.D., of the psychiatry department at the University of North Carolina School of Medicine and colleagues there and at the University of Pennsylvania School of Medicine. Their findings are reported in the August American Journal of Psychiatry.

The researchers studied 82 gay men who were HIV seropositive but clinically asymptomatic. The subjects, were between 18 and 51 years old, with an average age of 30.3 years. They had to have CD4 lymphocyte levels above 200 at the onset of the study and not be taking antiretroviral drugs. (A person with a CD4 level below 200 qualifies for a diagnosis of AIDS.) They also had to be free of "significant" medical disorders, such as heart, lung, or kidney disease, and pre-existing neurological disorders. The subjects were evaluated every six months for 7.5 years.

On the basis of ongoing assessments over the study period and data from other researchers pointing to risks for HIV progression, Leserman said her group hypothesized that "an increased risk of AIDS would be associated with more cumulative average stressful events, coping by means of denial, depressive symptoms, and higher cortisol levels as well as less cumulative average satisfaction with social support."

Leserman’s team decided to study cortisol as a risk factor after they found that at the time the research began, subjects "with high basal cortisol levels had significantly greater stress-associated changes in immune status than subjects with low basal cortisol levels."

The researchers found a particularly strong link between stressful life events that were not directly caused by the progression of their illness—excluded, for example, were a plunge in CD4 count or job retirement due to the HIV-related deterioration—and the risk of progressing to an AIDS diagnosis. Life events that were included, she told Psychiatric News, were such things as "experiencing the death of a close friend or relative, financial difficulties, a close friend’s health worsening, breaking up a romantic relationship, or moving a residence."

"For each 1-point increase in average cumulative average stressful life events, the risk of AIDS increased by 19 percent. For every 4-point increase in cumulative average stressful life events, the equivalent of one severe stressor or two moderate stressors, the risk of AIDS was doubled," Leserman noted.

The researchers rated stressful events on a five-point scale according to "the degree of threat most people would experience given the particular circumstances (e.g., financial impact, life threat, personal involvement)." Each of 111 possible stressors was rated and then "summed at each six-month time period," Leserman explained. "We then looked at the cumulative average before AIDS or at the end of the study."

A similar relationship turned up between how satisfied the HIV-infected subjects were with the social supports they believed they could count on and their risk of progressing from being asymptomatic to developing AIDS. The more satisfied they were with these supports, the less their risk was of developing AIDS-defining symptoms or signs.

Their hypothesis was borne out as well, the researchers point out, for the subjects’ use of denial as a coping mechanism. "For every one-unit increase in cumulative average coping through denial, the risk of AIDS was doubled," they note.

And on the measure of cortisol, the progression from HIV infection to AIDS also was hastened as cortisol levels increased. "Cortisol independently predicted disease progression to AIDS during the 7.5-year period," Leserman said. "For every 5 mg/dL increase in cortisol, the risk of developing AIDS was almost doubled." She hypothesized that "cortisol may directly stimulate HIV-1 viral replication, and it may alter the pattern of cytokines secreted." She observed as well that their findings "are consistent with those in depressed patients showing a negative relationship between cortisol and several measures of cellular immune status."

Now that they and other researchers have taken a giant step toward identifying risk factors for HIV disease progression, Leserman and her team acknowledged that more research is needed to see if medications or less formal types of intervention such as stress management programs can modify stressors to the point where they can alter the disease progression.