Sep. 11, 2000 CHAPEL HILL -- New research at the University of North Carolina at Chapel Hill shows that men infected with HIV will more rapidly develop AIDS if they use strategies of denial to cope with the disease threat.
The new study also linked higher average blood level of the stress hormone cortisol to speedier progression to AIDS. A report of the study appears in the August 1 issue of the American Journal of Psychiatry.
The 7 1/2 -year follow-up study extended by two years previous Carolina research with the same 82 HIV-infected men. The new study continued to demonstrate that an accumulation of stressful life events such as the death of friends and lack of social support were associated with faster disease progression.
"The results from the 5 1/2-year study were among the first to link stressful life events with progression to AIDS. This time we looked at the effects of coping strategies and the hormone cortisol, something that we had not looked at before," said Jane Leserman, PhD, research associate professor of psychiatry at UNC-CH School of Medicine. "These new findings carry important implications both for understanding the progression of AIDS and possible treatments for HIV."
At 7 1/2 years into the study, 37 percent of the men had developed AIDS -- that is, their CD4 immune "helper" T cell count dropped below 200 or they developed an AIDS clinical condition. Leserman and colleagues found that the men who had more cumulative stressful events, more denial in their coping with the threat of AIDS, less satisfaction with their social support and higher levels of cortisol were the ones who progressed faster to AIDS.
Specifically, the hazard of AIDS was about doubled for each average increase of one severe stress, for each average increase of one point in the denial scale (range 1-4), for each 1.5 point average decrease in the social support scale (range 1-6) and for each microgram per deciliter average increase in serum cortisol.
Leserman, who is part of a team of scientists from North Carolina, Florida and Pennsylvania, pointed out that one problem in doing HIV follow-up research is the difficulty in knowing where people are in the disease course when they enter the study. "When they get tested [for HIV] isn't necessarily near the time they became with the virus, " she notes.
In the earlier study, the researchers attempted to get a better grasp on this uncertainty by controlling for blood levels of CD4 T lymphocytes (a type of immune cell depleted by HIV) when each participant entered the study. For the current follow-up, the researchers were also able to control for viral load, the concentration of HIV in the blood, obtained from blood samples taken when each man first entered the study during 1990-1992. None of the men were on anti-retroviral drugs for HIV at that time.
Study participants were evaluated every six months in the medical school's General Clinical Research Center. Participants were asked to indicate on a 4-point scale how they "generally cope with or handle the threat of getting AIDS." The use of denial was indicated by such statements as, "I pretend that it hasn't really happened."
According to Leserman, the measure of stress is unique, not based on self-reported checklist responses. "We ask subjects to tell us about the circumstances in their life every six months. They indicate people who've died, if they've changed jobs, moved, or any other such stress that might occur to someone. And we interview them in detail about the circumstances - the financial impact, how close they were to the person who died, how long they lived with the partner before they broke up."
The researchers then apply a numerical rating to these circumstances, based on a manual of vignettes and norms. "In this way we know that the stress measure is independent of the subjects' perception and way of coping. It's a more objective measure," Leserman said. She and her colleagues note "this objective stress rating helps reduce the possibility that worsening disease may have led to poorer coping and higher stress scores."
In terms of all psychosocial variables measured, almost half of those who scored above the median in stress, above the median in denial, and below the median in social support progressed faster to AIDS during the 7 1/2 years. In comparison, only about one-quarter of those who were below the medians in stress and denial and above the median in social support progressed to AIDS. As to the possibility that cortisol is a factor in progression to AIDS, scientists currently disagree.
"Cortisol has generally been associated with decrements in immune response and in HIV its role is quite controversial," Leserman says. "Cortisol might trigger destruction of CD4 cells and may bolster HIV replication. But the literature is not consistent on this.
"Our data supports the idea that men who have high levels of cortisol over a long period of time seem to do worse," she adds. "If that's actually the case, we might think about research on treatments that lower cortisol in those with elevated levels."
But in terms of the new study's overall results, the message for Leserman remains clear.
"I think that once again we're finding that what's going on in people's lives -- the everyday stressors, the everyday psychosocial traumas, besides HIV -- can affect the course of illness. And if we can develop treatments to help people deal with stress and cope with stressful life events and HIV, perhaps we might see these as having some efficacy for the course of this disease. Along with considering the biological aspects of HIV, we should not ignore the relevance of psychological factors."
The National Institute of Mental Health, National Institutes of Health, provided financial support from the study. Technical assistance came from the UNC Center for AIDS Research.
(Writer: LESLIE H. LANG, UNC-CH School of Medicine)
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