Analyzing HADS data for two different participant strata (baseline scores above versus below the cut-off separating normal and pathological values) indicated that significant CBSM training effects were only observable in subjects above the cut-off score (Fig. 3). Effect sizes (d values) for differences between baseline and 12-month follow-up scores indicated a significant benefit for the CBSM group above the respective cut-off score (HADS anxiety, 1.2; HADS depression, 1.5), whereas effect size scores were all d < 0.2 in controls and in the CBSM group below cut-off.
We found no effects of CBSM training on morbidity, viral load and CD4 cell counts, and adherence to cART compared with standard medical care. However, we did observe benefits of CBSM training on quality of life and psychological distress. Notably, significant improvements in distress were only observable in individuals with high distress at baseline.
A strength of this trial was the inclusion of a group of HIV-infected persons from a routine practice clinical setting who were taking stable antiretroviral therapy and had restored cellular immunity. Further strengths include the longitudinal assessment of the clinically relevant markers of HIV infection, the use of an intervention according to a manual, and the recruitment at multiple study centers. Limitations are that the mode of group training might have affected the acceptability of the intervention, which would explain the fact that only a small proportion (6.1%) of eligible individuals actually agreed to participate. Other routes of administration with known efficacy, such as individual psychotherapy, might prove to be more accessible to HIV-infected persons who are unwilling to participate in group therapy sessions [31,32].
Our findings endorse previous reports on the efficacy of CBSM training in reducing psychological distress and enhancing quality of life in HIV-infected individuals [19,23], extending these findings to persons receiving cART. However, we were unable to find evidence for beneficial short- or long-term CBSM training effects on surrogate markers of HIV infection as previously reported by others [16,33,34]. These discrepancies between earlier studies and our controlled trial are unlikely to result from differences in the efficacy of the employed CBSM training, since effect sizes in the psychosocial outcome parameters were comparable. Although not directly comparable to our viral load effect size estimate, Antoni et al.  reported a 0.56 log10 copies/ml decrease in HIV viral load over 15 months in a CBSM training group after controlling for HIV medication adherence. However, these results were obtained in persons with substantial morbidity, including 54% with previous AIDS and 77.6% with detectable plasma HIV levels at baseline, who were on heterogeneous and nonsuppressive antiretroviral regimens.
The absence of an effect of CBSM on clinical markers may be explained by the relatively small contribution of psychosocial factors to HIV progression among persons on cART with complete viral suppression and restored immune function. Since a negative impact of psychological distress on HIV disease progression has been demonstrated in prospective studies with a follow-up of up to 9 years [1,2], effects of CBSM training on the clinical status might be observed in the long-term observation of HIV-infected individuals with high levels of psychological distress.
Our results indicate that CBSM group training is an efficacious and effective intervention for enhancing quality of life and psychological well-being in HIV-infected persons taking stable antiretroviral therapy with restored immunity and little somatic morbidity. Its beneficial effects are particularly observed among persons who present with depression and anxiety scores at baseline, which indicate high psychological distress. Therefore, screening for psychological distress  and referral to individually acceptable psychotherapeutic interventions should be integral to HIV management, if not all somatic diseases .
We are indebted to the participants and to the study nurses (Christina Grube, Anna Christen, Miriam Unger, Nicca Dunja, Susanne Stoelzl, and Andreas Egger) and the physicians of the participating HIV outpatient clinic at the University Hospital Zurich, the University Hospital Basel, University Hospital Bern, and the Cantonal Hospital St. Gallen, Switzerland, for patient care and data collection.
Members of the Swiss HIV Cohort Study group: M. Battegay, E. Bernasconi, H. Bucher, Ph. Bürgisser, M. Egger, P. Erb, W. Fierz, M. Fischer, M. Flepp (Chairman of the Clinical and Laboratory Committee), P. Francioli (President of the SHCS), H.J. Furrer, M. Gorgievski, H. Günthard, P. Grob, B. Hirschel, L. Kaiser, C. Kind, Th. Klimkait, B. Ledergerber, U. Lauper, M. Opravil, F. Paccaud, G. Pantaleo, L. Perrin, J.-C. Piffaretti, M. Rickenbach (Head of Data Centre), C. Rudin (Chairman of the Mother & Child Substudy), J. Schupbach, R. Speck, A. Telenti, A. Trkola, P. Vernazza (Chairman of the Scientific Board), Th. Wagels, R. Weber, and S. Yerly.
1. Ickovics J, Hamburger M, Vlahov D, Schoenbaum E, Schuman P, Boland RJ, et al
. Mortality, CD4 cell count decline, and depressive symptoms among HIV-seropositive women: longitudinal analysis from the HIV Epidemiology Research Study. JAMA 2001; 285:1466–1474.
2. Leserman J. HIV disease progression: depression, stress, and possible mechanisms. Biol Psychiatry 2003; 54:295–306.
3. Ickovics J, Milan S, Boland R, Schoenbaum E, Schuman P. Vlahov D. Psychological resources protect health: 5-year survival and immune function among HIV-infected women from four US cities. AIDS 2006; 20:1851–1860.
4. Young J, De Geest S, Spirig R, Flepp M, Rickenbach M, Furrer H, et al
. Stable partnership and progression to AIDS or death in HIV infected patients receiving highly active antiretroviral therapy: Swiss HIV cohort study. BMJ 2004; 328:15.
5. Cole S, Naliboff B, Kemeny ME, Griswold M, Fahey J, Zack J. Impaired response to HAART in HIV-infected individuals with high autonomic nervous system activity. Proc Natl Acad Sci USA 2001; 98:12695–12700.
6. Reynolds N, Testa M, Marc L, Chesney M, Neidig J, Smith S, et al
. Factors influencing medication adherence beliefs and self-efficacy in persons naive to antiretroviral therapy: a multicenter, cross-sectional study. AIDS Behav 2004; 8:141–150.
7. Fairfield K, Libman H, Davis RB, Eisenberg D. Delays in protease inhibitor use in clinical practice. J Gen Intern Med 1999; 14:395–401.
8. Komiti A, Judd F, Grech P, Mijch A, Hoy J, Lloyd JH, et al
. Suicidal behaviour in people with HIV/AIDS: a review. Aust N Z J Psychiatry 2001; 35:747–757.
9. Bing E, Burnam MA, Longshore D, Fleishman J, Sherbourne C, London A, et al
. Psychiatric disorders and drug use among human immunodeficiency virus-infected adults in the United States. Arch Gen Psychiatry 2001; 58:721–728.
10. Orlando M, Burnam MA, Beckman R, Morton S, London A, Bing E, et al
. Re-estimating the prevalence of psychiatric disorders in a nationally representative sample of persons receiving care for HIV: results from the HIV Cost and Services Utilization Study. Int J Meth Psychiatr Res 2002; 11:75–82.
11. Ciesla JA, Roberts J. Meta-analysis of the relationship between HIV infection and risk for depressive disorders. Am J Psychiatry 2001; 158:725–730.
12. Zinkernagel C, Taffe P, Rickenbach M, Amiet R, Ledergerber B, Volkart A, et al
. Importance of mental health assessment in HIV-infected outpatients. J Acquir Immune Defic Syndr 2001; 28:240–249.
13. Antoni M, Baggett L, Ironson G, Laperriere A, August S, Klimas N, et al
. Cognitive–behavioral stress management intervention buffers distress responses and immunologic changes following notification of HIV-1 seropositivity. J Consult Clin Psychol 1991; 59:906–915.
14. Antoni MH, Cruess DG, Cruess S, Lutgendorf S, Kumar M, Ironson G, et al
. Cognitive-behavioral stress management intervention effects on anxiety, 24-hr urinary norepinephrine output, and T-cytotoxic/suppressor cells over time among symptomatic HIV-infected gay men. J Consult Clin Psychol 2000; 68:31–45.
15. Antoni M, Cruess DG, Klimas N, Carrico A, Maher K, Cruess S, et al
. Increases in a marker of immune system reconstitution are predated by decreases in 24-h urinary cortisol output and depressed mood during a 10-week stress management intervention in symptomatic HIV-infected men. J Psychosom Res 2005; 58:3–13.
16. Antoni MH, Cruess D, Klimas N, Maher K, Cruess S, Kumar M, et al
. Stress management and immune system reconstitution in symptomatic HIV-infected gay men over time: effects on transitional naive T cells (CD4(+)CD45RA(+)CD29(+)). Am J Psychiatry 2002; 159:143–145.
17. Antoni MH, Cruess S, Cruess DG, Kumar M, Lutgendorf S, Ironson G, et al
. Cognitive–behavioral stress management reduces distress and 24-h urinary free cortisol output among symptomatic HIV-infected gay men. Ann Behav Med 2000; 22:29–37.
18. Carrico A, Antoni MH, Duran RE, Ironson G, Penedo F, Fletcher M, et al
. Reductions in depressed mood and denial coping during cognitive behavioral stress management with HIV-positive gay men treated with HAART. Ann Behav Med 2006; 31:155–164.
19. Carrico A, Antoni M, Pereira DB, Fletcher M, Klimas N, Lechner SC, et al
. Cognitive behavioral stress management effects on mood, social support, and a marker of antiviral immunity are maintained up to 1 year in HIV-infected gay men. Int J Behav Med 2005; 12:218–226.
20. Cruess D, Antoni M, Kumar M, Ironson G, Mccabe P, Fernandez J, et al
. Cognitive–behavioral stress management buffers decreases in dehydroepiandrosterone sulfate (DHEA-S) and increases in the cortisol/DHEA-S ratio and reduces mood disturbance and perceived stress among HIV-seropositive men. Psychoneuroendocrinology 1999; 24:537–549.
21. Cruess DG, Antoni MH, Schneiderman N, Ironson G, Mccabe P, Fernandez J, et al
. Cognitive-behavioral stress management increases free testosterone and decreases psychological distress in HIV-seropositive men. Health Psychol 2000; 19:12–20.
22. Cruess S, Antoni M, Cruess D, Fletcher M, Ironson G, Kumar M, et al
. Reductions in herpes simplex virus type 2 antibody titers after cognitive behavioral stress management and relationships with neuroendocrine function, relaxation skills, and social support in HIV-positive men. Psychosom Med 2000; 62:828–837.
23. Lechner S, Antoni MH, Lydston D, Laperriere A, Ishii M, Devieux J, et al
. Cognitive–behavioral interventions improve quality of life in women with AIDS. J Psychosom Res 2003; 54:253–261.
24. Lutgendorf S, Antoni MH, Ironson G, Klimas N, Kumar M, Starr K, et al
. Cognitive–behavioral stress management decreases dysphoric mood and herpes simplex virus-type 2 antibody titers in symptomatic HIV-seropositive gay men. J Consult Clin Psychol 1997; 65:31–43.
25. Lutgendorf S, Antoni MH, Ironson G, Starr K, Costello N, Zuckerman M, et al
. Changes in cognitive coping skills and social support during cognitive behavioral stress management intervention and distress outcomes in symptomatic human immunodeficiency virus (HIV)-seropositive gay men. Psychosom Med 1998; 60:204–214.
26. Wittchen H, Pfister H. DIA-X Interviews: Manual für Screening-Verfahren und Interview. Frankfurt: Swets & Zeltinger; 1997.
27. Wu A, Hays R, Kelly S, Malitz F, Bozzette S. Applications of the Medical Outcomes Study health-related quality of life measures in HIV/AIDS. Qual Life Res 1997; 6:531–554.
28. Zigmond A, Snaith RP. The hospital anxiety and depression scale. Acta Psychiatr Scand 1983; 67:361–370.
29. Knobel H, Alonso J, Casado JL, Collazos J, Gonzalez J, Ruiz I, et al
. Validation of a simplified medication adherence questionnaire in a large cohort of HIV-infected patients: the GEEMA Study. AIDS 2002; 16:605–613.
30. Cohen J. Statistical power analysis for behavioral sciences. Hillsdale, NJ: Lawrence Erlbaum; 1988.
31. Markowitz J, Kocsis J, Fishman B, Spielman L, Jacobsberg L, Frances AJ, et al
. Treatment of depressive symptoms in human immunodeficiency virus-positive patients. Arch Gen Psychiatry 1998; 55:452–457.
32. Weber R, Christen L, Christen S, Tschopp S, Znoj H, Schneider C, et al
. Effect of individual cognitive behaviour intervention on adherence to antiretroviral therapy: prospective randomized trial. Antivir Ther 2004; 9:85–95.
33. Belanoff J, Sund B, Koopman C, Blasey C, Flamm J, Schatzberg A, et al
. A randomized trial of the efficacy of group therapy in changing viral load and CD4 counts in individuals living with HIV infection. Int J Psychiatry Med 2005; 35:349–362.
34. Antoni MH, Carrico A, Duran RE, Spitzer S, Penedo F, Ironson G, et al
. Randomized clinical trial of cognitive behavioral stress management on human immunodeficiency virus viral load in gay men treated with highly active antiretroviral therapy. Psychosom Med 2006; 68:143–151.
35. Arroll B, Khin N, Kerse N. Screening for depression in primary care with two verbally asked questions: cross sectional study. BMJ 2003; 327:1144–1146.
36. Prince M, Patel V, Saxena S, Maj M, Maselko J, Phillips M, et al
. No health without mental health. Lancet 2007; 370:859–877.