These results provide evidence that even in the era of powerful HAART medications, psychosocial variables still account for significant variation in CD4 cell number and do so for VL as well. The results provide valuable confirmation of earlier studies (6
) that established these relationships for depression, negative life events, and coping before the availability of HAART. In addition to depression, our results establish that hopelessness and denial/avoidant coping have significant relationships with both CD4 and VL changes over time and extend findings to both men and women with access to HAART throughout the entire period of the study. This is the first study of which we are aware that establishes a prospective relationship between hopelessness, denial/avoidant coping, life event stress, and accelerated rate of increase in VL. (A prospective relationship between depression and VL has previously been noted for women (8
).) In fact, plasma VLs may be more sensitive to psychological influences than CD4, as indicated by higher increase and decline ratios.
Although many studies have found that depression and other psychological variables predict disease progression in HIV, none, to our knowledge, have controlled for adherence. This has become particularly important in the era of HAART as it has been estimated that adherence rates of up to 95% are required for achieving and maintaining viral suppression (26
). It is interesting to note that in our study, medication adherence was significantly related to VL change, but not to CD4 change. Although the reason for this is not known, it raises the possibility that VL may be more immediately responsive to antiretroviral medications than CD4 cell reconstitution, which may require a longer period of time.
Our results provide information on the predictive relationships from both baseline and repeated measures of stress, distress, and coping. The presence of a significant relationship between cumulative avoidant coping with rate of CD4 change over time compared with the absence of a significant relationship with baseline supports the use of repeated assessments over time. The superior predictive power of repeated measures over baseline measures has been noted by others (5
) and may help to explain some of the contrary findings relating depression to disease progression when depression was only measured at baseline (47
Surprisingly, not only did no significant results emerge between social support and disease progression but a nonsignificant trend was observed whereby higher levels of baseline social support predicted more rapid CD4 decline. This puzzling result has some support in the existent literature (20
) but is not consistent with results of several other studies which identified beneficial relationships (4
). Subsequent analyses of our data revealed that higher levels of social support were associated with being sexually active (r
= 0.27, p
< .001) (assessed through interview) but were not associated with unsafe sex practices (r
= 0.00, not significant). Notable aspects of this study that may be related to the absence of social support findings include the restriction of study participants to those in the midrange of disease, the exclusion of IV and dependent drug users, and the use of a measure that has items but not subscales for emotional, instrumental, and informational support.
Education was the only sociodemographic covariate significantly related both to rate of CD4 and VL change. The SES-health gradient is well established in the general literature (48
), but this study is the first of which we are aware to predict changes in both biological markers of disease progression in HIV.
There are a number of plausible behavioral and biological mechanisms that have been suggested in explaining the link between depression/stress and disease progression (5
). In this sample, adherence to medication does not explain the effect. Alterations in the hypothalamic-pituitary-adrenocortical system, including cortisol, have been demonstrated both in stress and depression, have been predictive of faster disease progression in HIV (4
), and may stimulate HIV replication (50
). Similarly, products of the sympathetic nervous system (norepinephrine) become elevated during stress and have been shown to enhance HIV viral replication in vitro (51
). Important immune variables, including cytotoxic T lymphocytes and natural killer cells, undergo change during depression in HIV patients and have been related to symptom onset and disease progression in HIV (53
Although psychosocial variables were related to important markers of disease progression (i.e., CD4, HIV VL) that are known to predict clinical outcomes (21
), the relatively short follow-up time of this study precluded predicting to clinical symptoms or death. The longitudinal design allows for the statement of predictive but not necessarily causal relationships between our baseline psychosocial variables and disease progression markers. Another limitation of the study was that the psychosocial (e.g., negative life events) and control (e.g., medication adherence) measures are based on self-reports and are vulnerable to the biases of that methodology. For example, it has been reported that life events stress measured by interview predicts CD4 change (3
), whereas the present study using self-report assessment did not (although it did predict to VL). Finally, although changes in depression were carefully measured across assessments, the treatment of depression was not tracked and was not part of these analyses.
Conclusions and Future Directions
In summary, the present study demonstrated that several psychosocial factors contribute to the variance in HIV disease progression even in the present era of HAART medication. In particular, feelings of hopelessness, depressed mood, and avoidant coping predict an accelerated decline in CD4 cells and an increase in HIV VL. Pharmacologic (55
) and behavioral treatments (57
) have been shown to decrease depression in HIV patients. To the extent that these treatments may also attenuate both depressed affect and disease progression, large scale clinical intervention trials are needed to determine whether reducing distress and hopelessness, and improving adaptive coping skills in HIV infected individuals can decrease disease progression. Recent findings from a study of stress management in gay men with HIV (59
) suggests that this may be the case, at least for VL.
Thanks to Kelly Detz for data management and to Annie George for conducting many of the interviews.