Depression Linked to HIV Progression, Death in Women

HIV-positive women with symptoms of chronic depression are twice as likely to die of AIDS-related complications than HIV-positive women who report limited or no depressive symptoms, according to a study of 765 women published in yesterday's Journal of the American Medical Association. Chronic depression was also associated with a decline in CD4+ cell counts. Researchers led by Dr. Jeannette Ickovics of Yale University used data from the HIV Epidemiologic Research Study (HERS), including information collected from April 1993 through March 2000 from women at four sites: Johns Hopkins School of Hygiene and Public Health in Baltimore, Md., Montefiore Medical Center in Bronx, N.Y., Brown University in Providence, R.I., and Wayne State University School of Medicine in Detroit, Mich. Study participants were between the ages of 19 and 55; 62% were black, 21% were white and 18% were Hispanic or of another race or ethnicity. Forty-five percent of the participants had not completed high school, 84% were unemployed and 74% reported an annual household income equal to or under $12,000. HIV-related mortality was calculated from a review of medical records and confirmed utilizing individual death certificates and the National Death Index. The "primary objective" of the study was to "determine whether depressive symptoms were associated with mortality among women with HIV" and to examine the possible link between depression and a decline in CD4+ cell count.

Determining Severity of Depression
At each clinic visit, participants self-administered the Center for Epidemiologic Studies Depression Scale exam (CES-D), which contains 20 questions about depressive symptoms experienced in the past seven days. The tests were modified to remove questions about somatic complaints, such as poor appetite and lack of energy, that are also symptoms of HIV. Scores greater than 16 are defined as "probable cases of depression," with approximately 20% of the general population falling within this category. Respondents were classified as chronically depressed if they scored a 16 or higher during at least 75% of their study visits. Subjects with scores of 16 or higher 26% to 74% of the time were classified as having "intermittent depressive symptoms." Forty-two percent of respondents were characterized as having symptoms of chronic depression, while an additional 35% showed signs of intermittent depression and 23% had "limited" or no depressive symptoms. Mean CES-D scores remained "relatively stable" for the duration of the study, indicating that depression severity did not increase over time.

Depression as a Predictor of Death
One hundred and six women died of HIV-related causes during the seven-year study. The highest percentage (23%) of women who died were among those with chronic depressive symptoms. Sixteen percent of women with intermittent symptoms died, while 8% of those with limited or no symptoms died. Participants who died typically had lower baseline CD4+ cell counts, higher viral loads, a greater number of HIV-related symptoms and did not receive highly active antiretroviral therapy at baseline. Women who were 35 years old or older and those who were unemployed at the beginning of the study were 1.5 and 2.0 times more likely than younger and employed participants to die. Even after using a Cox proportional hazards model to control for "potential confounding" variables, women who expressed symptoms of chronic depression were still two times more likely to die than women with limited or no symptoms. Fifty-four percent of women with symptoms of chronic depression and an initial CD4+ cell count of lower than 200 died during the study, as did 48% with intermittent symptoms and 21% with limited or no symptoms.

Conclusions
The researchers note that evaluating the cause and effect relationship between depression and HIV progression is "complex" because symptoms for both conditions "overlap" and the symptoms of depression could be attributed to HIV disease progression. But they point out that even those reporting no HIV-related symptoms at the study's baseline and who were chronically depressed were 3.6 times more likely to die than those with no HIV symptoms and limited or no depressive symptoms. The results, "although not conclusive," suggest that depression "contribute[s] uniquely to mortality and [is] not simply an artifact of declining health," the researchers write. Depression may also have an indirect effect on mortality because of its association with "damaging behaviors," such as smoking and alcohol use. The researchers note that the study was limited by the use of the self-reported CES-D screening tests, but point out that the study was large and recruited participants from diverse geographic areas. Health care providers should "recognize the risks of depression for disease progression and mortality among women with HIV," the researchers write. Identifying and targeting these women for monitoring and treatment may be "critical," they continue, as antidepressant drugs have been shown to be effective and "well tolerated" among patients with HIV. Further research into the effects of depression on disease progression is needed not only in the case of HIV, but in other chronic diseases as well, the researchers conclude (Ickovics et al., JAMA, 3/21).