Psychoneuroimmunology and HIV Disease Progression
Psychoneuroimmunology and HIV Disease Progression
Among psychiatrists who treat patients with HIV/AIDS, the question of how psychosocial distress effects the progression of HIV disease is likely to arise. Even for healthy individuals, we are only beginning to clarify the complex pathways by which thoughts and emotions impact immune function. Due to the bidirectionality of the communications of the brain and the immune system, this is a complicated scenario. The fact that HIV alters the function of the immune system during the course of its progression creates greater confounds to the understanding of these systems. We will address the rationale that progression from HIV infection to AIDS may be modulated by psychosocial factors, discuss possible reasons for conflicting findings and posit some clinically relevant recommendations drawn from research findings.
Psychosocial Variables: Modulators of HIV Disease Progression?
The progression of HIV disease is highly variable among individuals. Factors known to play a role in determining the rate of progression include the viral strain, genetic characteristics of the host immune system, co-infections with other pathogenic organisms (Zorilla et al., 1996) and health maintenance habits (e.g., diet, exercise, medical treatment). However, these factors do not fully explain the extreme degree of variability noted in the course of HIV disease (Cole and Kemeny, 1997).
Given that certain immune parameters are modulated by physiologic mediators of the stress response (i.e., catecholamines and glucocorticoid hormones), it would seem logical to investigate the role of stress and other psychosocial factors in the progression of HIV infection. In fact, changes in immune function and disease susceptibility have been well documented in healthy individuals during times of psychic distress (Ader et al., 1995; Miller et al., 1997), and studies over the past 15 years have shown significant correlations between psychosocial variables and HIV progression. However, there have also been a number of studies showing no such correlation.
Stressful Life Experiences. Studies examining stressful life events and HIV have shown interesting but conflicting results. For example, Rabkin et al. (1991) studied 124 HIV-positive men and found no association between clinician-rated anxiety and CD4+ lymphocyte counts at study entry and at six-month follow-up. However, Evans et al. (1995), performing a similar cross-sectional study of HIV-positive men, did show a significant correlation between increased frequency of negative life events over the six months prior to interview and decreased CD8+ cytotoxic T-cells. Evans et al. (1997) continued with a two-year prospective study and found that not only were severe life stressors predictive of greater declines in some lymphocyte populations (natural killer [NK] cells and CD8+ cytotoxic lymphocytes), but also that such stressors increased the rate of HIV progression to AIDS. The researchers emphasized that their results were noted only in those experiencing severe life stress, not stresses associated with everyday living. For every severe life stress reported, they found the risk of HIV disease progression to AIDS doubled. In their most recent work, these investigators followed 82 HIV-positive gay men at six-month intervals for up to 5.5 years. They found that more cumulative life stress and less cumulative social support doubled or tripled the probability of progressing to AIDS (Leserman et al., 1999).
Depression. Studies examining the effect of depression on HIV progression have had variable results. For example, Rabkin et al. (1991) found no correlation in their cross-sectional study between depression and CD4+ lymphocyte count or stage of HIV illness; however, a relationship was found between clinician-rated depression and increased report of HIV-related symptoms. In 1993, Burack et al. reported findings of a five-year prospective cohort study that showed a significant correlation between depressive symptoms and more rapid decline in CD4+ lymphocyte counts, although not with increased HIV/AIDS-related morbidity or mortality. Conversely, in a similar eight-year study of 1,809 HIV-positive gay men, Lyketsos et al. (1993) found no significant relationship between depression and indicators of HIV disease progression or clinical outcome. Likewise, results from a seven-year prospective cohort study of 402 gay men showed that depressed affect was associated with a greater AIDS-related mortality rate, although no correlation was found for measures of CD4+ lymphocytes (Mayne et al., 1996). In a meta-analytic review, Zorilla et al. (1996) concluded that no significant correlations could be made between depressive symptoms and markers of HIV disease progression. There did seem to be a relationship between depression and increased reporting of HIV-related symptoms.
Social Interaction. It is widely accepted that social isolation is a significant risk factor for several disease entities and that significant interruptions in social relationships can have deleterious effects. With regard to HIV/AIDS, this is exemplified among studies examining the death of an intimate partner, an event generally associated with bereavement and social role disruption.
Kemeny et al. (1995) studied 39 HIV-positive gay men who had experienced the death of an intimate partner within the previous 13 months. Looking at various markers of HIV progression pre- and postbereavement, they found significant increases in serum neopterin (a product of activated monocytes and a predictor of HIV disease progression) in the bereaved group. This finding was independent of ratings of depression, suggesting a qualitative difference between bereavement and depressive disorders. Another study unexpectedly found that greater self-reports of loneliness were associated with a slower decline in CD4+ lymphocytes over a three-year period, but not associated with time to AIDS diagnosis or AIDS-related death (Miller et al., 1997).
Similarly, in a study of socially and independently housed rhesus monkeys, Capatinio and Lerche (1998) found that greater social disruption around the time of inoculation with simian immunodeficiency virus correlated with a significantly increased rate of mortality. The rate of mortality also increased after inoculation if the animal was placed in a novel social environment versus individual housing. These findings, although yielding a variability of findings, suggest that social interactions may play an increasingly important role in understanding HIV disease progression.
Coping Responses. There is growing evidence that one's coping style may modulate the progression of HIV infection. For example, in a study by Byrnes et al. (1998), an increased measure of pessimism was related to lower NK-cell cytotoxicity in a group of HIV-seropositive black women at risk for cervical cancer. Furthering this hypothesis, Cole et al. (1996) found in a nine-year study that the degree of "closetedness," or concealment of gay identity, was strongly correlated with more rapid decline of CD4+ lymphocytes, more rapid progression to AIDS diagnosis and more rapid time to AIDS-related mortality. These findings were unrelated to health practices, medical treatment or other demographic differences and suggest a relationship between disease progression, poor coping and the stress of concealing one's sexual orientation.
Examining specific coping styles in a group of 74 gay men diagnosed with AIDS, Reed et al. (1994) showed that higher measures of "realistic acceptance" of their AIDS diagnosis was a significant predictor of decreased survival time. They point out that, in the past, researchers have shown unrealistic optimism to be associated with better psychological adjustment and more active coping styles. Studies of the converse of this idea have found a "fighting spirit" to be associated with reduced progression to AIDS over a 12-month period (Solano et al., 1993). In an examination of the impact of perceived causes of events on HIV progression, Segerstrom et al. (1996) showed that the tendency to attribute negative events to the self was predictive of faster CD4+ lymphocyte decline over the 18-month study period.