HIV-Associated Neurocognitive Dysfunction: Relationships with Coping, Psychological Distress, and Mortality

Neurocognitive dysfunction is a prevalent and disabling consequence of living with Human Immunodeficiency Virus (HIV) infection. To date, there is a dearth of conceptual models depicting interrelationships among HIV-associated neurocognitive dysfunction, coping strategies, and psychological distress. Additionally, it remains unclear whether HIV-associated neurocognitive impairment (NCI) is a predictive marker of early mortality during the era of antiretroviral (ARV) medication availability, especially among individuals who are in the mid-range of their illness, prior to advanced disease progression. The present thesis is comprised of two studies intended to address these gaps in the literature. Study 1 and Study 2 both utilized an ethnically diverse sample of 209 HIV-positive men and women (Mage=37.69; 72% male; 67% attending some college or more) predominantly in the mid-range of their illness (MCD4=323.02 cells/mm3, range: 150-700 cells/mm3; no previous AIDS-defining symptoms). Study 1 sought to examine whether poorer global cognitive status and poorer executive control were each related to elevated psychological distress through greater use of avoidant coping strategies and diminished use of cognitively-oriented coping strategies, using structural regression methodology. Global cognitive status was measured using the HIV-dementia scale (HDS), and executive control was measured with the Trail Making Test B-A completion time; avoidant coping (i.e., denial and behavioral disengagement) and cognitive coping (acceptance and cognitive reappraisal) were measured using subscales of the brief-COPE; a composite measure of psychological stress was indicated by measures of depressive symptoms (BDI), anxiety symptoms (STAI-S), and HIV-related distressing thoughts (IES). Study 2 aimed to determine whether global NCI (HDS total score \u3c 10) and poorer executive control were each independently related to greater mortality risk over a follow-up duration of up-to 13 years. In both studies, demographic (i.e., age, gender, African American race/ethnicity, education) and disease-related (i.e., CD4 lymphocyte count, viral load, ARV medication regimen status) covariates were included. Results of Study 1 showed that the hypothesized model fit the data (χ2=21.83, CFI=.99, RMSEA=.03, SRMR=.03) and indicated that lower HDS score was significantly related to greater avoidant coping (β=-.22, pp=.048). In turn, greater avoidant coping (β=.30, ppp=.01). Poorer executive control was indirectly associated with greater psychological distress through avoidant coping. Study 2 revealed that 31 (15%) subjects scored in the NCI range at baseline, and 58 subjects (28%) died during the study. Participants with NCI at baseline were significantly more likely to die during the follow-up period (median=11 years) compared with their cognitively within normal limits (WNL) counterparts (HR: 2.10; 95% confidence interval, 1.10, 4.00), controlling for covariates. Executive control was not related to mortality. The findings of Study 1 indicate that poorer HIV-associated neurocognitive functioning is linked to maladaptive coping behaviors, which are in turn related to greater psychological distress. These novel findings suggest that HIV-associated neurocognitive changes might influence coping behavior, and highlight the utility of assessing cognitive functioning (especially using the HDS) as an important correlate of emotional well-being in HIV-positive patients. Therefore, patients with HIV-associated neurocognitive dysfunction may benefit from aggressive intervention efforts targeting coping skills, especially those which are avoidant in nature. Study 2 demonstrated that subjects scoring in the NCI range on the HDS were twice as likely to die during the (up to) 13-year study period than subjects scoring in the WNL range, independent of demographics and key illness variables previously associated with mortality. This study confirms previous reports that HIV-associated NCI is an independent marker of morality risk, and extends this finding to a diverse sample of patients predominantly in the mid-range of illness, without AIDS-defining symptoms. This finding suggest that the HDS can be utilized as brief screening measure that offers potential prognostic utility for assessing mortality risk in HIV. Moreover, it extends previous literature by identifying NCI as an independent marker of mortality risk among HIV-positive adults without advanced immunological compromise, during the era of highly active ARV availability