Progression to AIDS, a clinical AIDS condition and mortality: psychosocial and physiological predictors

Background. The primary aim of this study is to examine prospectively the association of stressful life events, social support, depressive symptoms, anger, serum cortisol and lymphocyte subsets with changes in multiple measures of human immunodeficiency virus (HIV) disease progression. Methods. Ninety-six HIV-infected gay men without symptoms or anti-retroviral medication use at baseline were studied every 6 months for up to 9 years. Disease progression was defined in three ways using the Centers for Disease Control (CDC) classifications (e.g. AIDS, clinical AIDS condition and mortality). Cox regression models with time-dependent covariates were used, adjusting for control variables (e.g. race, age, baseline, CD4 T cells and viral load, number of anti-retroviral medications). Results. Higher cumulative average stressful life events and lower cumulative average social support predicted faster progression to both the CDC AIDS classification and a clinical AIDS condition. Higher anger scores and CD8 T cells were associated with faster progression to AIDS, and depressive symptoms were associated with faster development of an AIDS clinical condition. Higher levels of serum cortisol predicted all three measures of disease progression. Conclusions. These results suggest that stressful life events, dysphoric mood and limited social support are associated with more rapid clinical progression in HIV infection, with serum cortisol also exerting an independent effect on disease progression.

[1]  M. Schroll,et al.  Hostility, incidence of acute myocardial infarction, and mortality in a sample of older Danish men and women. , 1995, American journal of epidemiology.

[2]  B. Moss,et al.  CD8+ T lymphocytes of patients with AIDS maintain normal broad cytolytic function despite the loss of human immunodeficiency virus-specific cytotoxicity. , 1990, Proceedings of the National Academy of Sciences of the United States of America.

[3]  H. Gu,et al.  Impact of stressful life events, depression, social support, coping, and cortisol on progression to AIDS. , 2000, The American journal of psychiatry.

[4]  W Winkelstein,et al.  Comorbidity and survival in HIV-infected men in the San Francisco Men's Health Survey. , 1996, Annals of epidemiology.

[5]  A. Sapse.  Cortisol, high cortisol diseases and anti-cortisol therapy , 1997, Psychoneuroendocrinology.

[6]  M. van Eck,et al.  The Effects of Perceived Stress, Traits, Mood States, and Stressful Daily Events on Salivary Cortisol , 1996, Psychosomatic medicine.

[7]  C. Hallahan,et al.  Maintenance of Large Numbers of Virus-Specific CD8+ T Cells in HIV-Infected Progressors and Long-Term Nonprogressors , 2000, The Journal of Immunology.

[8]  E. Bosmans,et al.  A further exploration of the relationships between immune parameters and the HPA-axis activity in depressed patients , 1991, Psychological Medicine.

[9]  A. Fauci,et al.  Lack of evidence for the dichotomy of TH1 and TH2 predominance in HIV-infected individuals. , 1994, Science.

[10]  Samuel M. Schulman,et al.  Social Support and the Development of Immune Function in Human Immunodeficiency Virus Infection , 1995, Psychosomatic medicine.

[11]  R. Detels,et al.  CD8+ T-lymphocyte activation in HIV-1 disease reflects an aspect of pathogenesis distinct from viral burden and immunodeficiency. , 1998, Journal of acquired immune deficiency syndromes and human retrovirology : official publication of the International Retrovirology Association.

[12]  Shirley J. Semple,et al.  Relationship of psychosocial factors to HIV disease progression , 1996, Annals of behavioral medicine : a publication of the Society of Behavioral Medicine.

[13]  S. Cohen,et al.  Stress and immunity in humans: a meta‐analytic review. , 1993, Psychosomatic medicine.

[14]  Eric R. Ziegel,et al.  Survival analysis using the SAS system , 1995 .

[15]  W. Paul.  Reexamining AIDS research priorities , 1995, Science.

[16]  Shelley E. Taylor,et al.  Social relationships and immune processes in HIV seropositive gay and bisexual men , 1997, Annals of behavioral medicine : a publication of the Society of Behavioral Medicine.

[17]  N. Schneiderman,et al.  Distress, denial, and low adherence to behavioral interventions predict faster disease progression in gay men infected with human immunodeficiency virus , 1994, International journal of behavioral medicine.

[18]  R. Gallo,et al.  Hydrocortisone and some other hormones enhance the expression of HTLV‐III , 1986, International journal of cancer.

[19]  B. Swanson,et al.  Cortisol upregulates HIV p24 antigen production in cultured human monocyte-derived macrophages. , 1998, The Journal of the Association of Nurses in AIDS Care : JANAC.

[20]  M. Clerici,et al.  A possible role for the cortisol/anticortisols imbalance in the progression of human immunodeficiency virus , 1997, Psychoneuroendocrinology.

[21]  M. de Carli,et al.  Ability of HIV to promote a TH1 to TH0 shift and to replicate preferentially in TH2 and TH0 cells. , 1994, Science.

[22]  Irwin G. Sarason,et al.  A Brief Measure of Social Support: Practical and Theoretical Implications , 1987 .

[23]  P. Corley.  Acquired immune deficiency syndrome: the glucocorticoid solution. , 1996, Medical hypotheses.

[24]  R. Williams,et al.  Hostility, CHD incidence, and total mortality: a 25-year follow-up study of 255 physicians. , 1983, Psychosomatic medicine.

[25]  Andrew H. Miller,et al.  Depression, natural killer cell activity, and cortisol secretion , 1991, Biological Psychiatry.

[26]  N. Schneiderman,et al.  Disparities in psychological, neuroendocrine, and immunologic patterns in asymptomatic HIV-1 seropositive and seronegative gay men , 1991, Biological Psychiatry.

[27]  P. Costa,et al.  Components of hostility as predictors of sudden death and myocardial infarction in the Multiple Risk Factor Intervention Trial. , 1989, Psychosomatic medicine.

[28]  E. McDaniel.  Social Origins of Depression: A Study of Psychiatric Disorder in Women , 1980 .

[29]  B. H. Fox,et al.  The role of psychological factors in cancer incidence and prognosis. , 1995, Oncology.

[30]  John W. Ward,et al.  1993 revised classification system for HIV infection and expanded surveillance case definition for AIDS among adolescents and adults. , 1993, MMWR. Recommendations and reports : Morbidity and mortality weekly report. Recommendations and reports.

[31]  D. Perkins,et al.  Severe stress, depressive symptoms, and changes in lymphocyte subsets in human immunodeficiency virus-infected men. A 2-year follow-up study. , 1997, Archives of general psychiatry.

[32]  J. Gorman,et al.  Glucocorticoid level and neuropsychiatric symptoms in homosexual men with HIV infection. , 1991, The American journal of psychiatry.

[33]  M. Opravil,et al.  Are immunological markers, social and personal resources, or a complaint‐free state predictors of progression among HIV‐infected patients? , 1997, Acta psychiatrica Scandinavica.

[34]  S. Perry,et al.  Relationships over 1 year between lymphocyte subsets and psychosocial variables among adults with infection by human immunodeficiency virus. , 1992, Archives of general psychiatry.

[35]  D. Feaster,et al.  Bereavement is associated with time-dependent decrements in cellular immune function in asymptomatic human immunodeficiency virus type 1-seropositive homosexual men , 1996, Clinical and diagnostic laboratory immunology.

[36]  J. Leserman.  The effects of depression, stressful life events, social support, and coping on the progression of HIV infection , 2000, Current psychiatry reports.

[37]  P. Butow,et al.  Psychosocial predictors of survival in metastatic melanoma. , 1999, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[38]  A. Fauci,et al.  Natural killer cells from human immunodeficiency virus (HIV)-infected individuals are an important source of CC-chemokines and suppress HIV-1 entry and replication in vitro. , 1998, The Journal of clinical investigation.

[39]  H. Morgenstern,et al.  Depressive Symptoms as Predictors of Medical Outcomes in HIV Infection , 1993 .

[40]  R. Kimerling,et al.  Traumatic stress in HIV-infected women. , 1999, AIDS education and prevention : official publication of the International Society for AIDS Education.

[41]  E. Bosmans,et al.  Increased serum soluble CD8 or suppressor/cytotoxic antigen concentrations in depression: Suppressive effects of glucocorticoids , 1996, Biological Psychiatry.

[42]  R. Daynes,et al.  Locally active steroid hormones may facilitate compartmentalization of immunity by regulating the types of lymphokines produced by helper T cells. , 1991, Research in immunology.

[43]  Michael W. Bridges,et al.  Person variables and health: personality predispositions and acute psychological states as shared determinants for disease. , 1995, Psychosomatic medicine.

[44]  B. Dohrenwend,et al.  Exemplification of a method for scaling life events: the Peri Life Events Scale. , 1978, Journal of health and social behavior.

[45]  D. Perkins,et al.  Stress-associated reductions of cytotoxic T lymphocytes and natural killer cells in asymptomatic HIV infection. , 1995, The American journal of psychiatry.

[46]  I. Gust,et al.  Acquired immune deficiency syndrome , 1983, The Medical journal of Australia.

[47]  B. Walker,et al.  Human immunodeficiency virus type 1-specific cytotoxic T lymphocytes release gamma interferon, tumor necrosis factor alpha (TNF-alpha), and TNF-beta when they encounter their target antigens , 1993, Journal of virology.

[48]  J. Gorman,et al.  Cortisol levels, immune status, and mood in homosexual men with and without HIV infection. , 1993, The American journal of psychiatry.

[49]  M. Bertini,et al.  Psychosocial factors and clinical evolution in HIV-1 infection: a longitudinal study. , 1993, Journal of psychosomatic research.

[50]  J. Ceuppens,et al.  Evidence for circulating activated cytotoxic T cells in HIV‐infected subjects before the onset of opportunistic infections , 1990, Clinical and Experimental Immunology.

[51]  J. Hoxie,et al.  Natural killer cell‐mediated lysis of T cell lines chronically infected with HIV‐1 , 1990, Clinical and experimental immunology.

[52]  G. Trinchieri,et al.  C1.7 antigen expression on CD8+ T cells is activation dependent: increased proportion of C1.7+CD8+ T cells in HIV-1-infected patients with progressing disease. , 1999, Journal of immunology.

[53]  D. Perkins,et al.  High Versus Low Basal Cortisol Secretion in Asymptomatic, Medication-free HIV-infected Men: Differential Effects of Severe Life Stress on Parameters of Immune Status , 2000, Behavioral medicine.

[54]  E. Vittinghoff,et al.  Depressive affect and survival among gay and bisexual men infected with HIV. , 1996, Archives of internal medicine.

[55]  S. Cohen,et al.  Depression and immunity: a meta-analytic review. , 1993, Psychological bulletin.

[56]  R. Daynes,et al.  Steroids as regulators of the mammalian immune response. , 1995, The Journal of investigative dermatology.

[57]  W. Mason,et al.  Social stress results in altered glucocorticoid regulation and shorter survival in simian acquired immune deficiency syndrome. , 1998, Proceedings of the National Academy of Sciences of the United States of America.

[58]  J. Giorgi,et al.  Circulating HIV-specific CD8+ cytotoxic T cells express CD38 and HLA-DR antigens. , 1993, Journal of immunology.

[59]  D. Vlahov,et al.  Mortality, CD4 cell count decline, and depressive symptoms among HIV-seropositive women: longitudinal analysis from the HIV Epidemiology Research Study. , 2001, JAMA.

[60]  D. Perkins,et al.  Progression to AIDS: the effects of stress, depressive symptoms, and social support. , 1999, Psychosomatic medicine.

[61]  S. Moretti,et al.  CD8 lymphocytes in HIV infection: helpful and harmful. , 1997, Journal of clinical & laboratory immunology.

[62]  P. Allison.  Survival analysis using the SAS system : a practical guide , 1995 .

[63]  H. Ullum,et al.  Natural immunity and HIV disease progression. , 1999, AIDS.

[64]  Overall and cause-specific mortality in a cohort of homo-/bisexual men, injecting drug users, and female partners of HIV-infected men. Pulmonary Complications of Human Immunodeficiency Virus Infection Study Group. , 1996, AIDS.

[65]  M. Hamilton.  A RATING SCALE FOR DEPRESSION , 1960, Journal of neurology, neurosurgery, and psychiatry.

[66]  A. Fauci,et al.  Multifactorial nature of human immunodeficiency virus disease: implications for therapy. , 1993, Science.

[67]  D. Perkins,et al.  Longitudinal study of social support and social conflict as predictors of depression and dysphoria among HIV‐positive and HTV‐negative gay men , 1994 .

[68]  M. Kemeny,et al.  Effects of AIDS-related bereavement on HIV progression among New York City gay men. , 1995, AIDS education and prevention : official publication of the International Society for AIDS Education.

[69]  D. Perkins,et al.  Severe life stress as a predictor of early disease progression in HIV infection. , 1997, The American journal of psychiatry.

[70]  B. Walker,et al.  Cytotoxic T lymphocytes against HIV. , 1990, AIDS.