We categorized trauma as high when one or more of the five traumatic events were endorsed. The economic hardship variable had two components: food insecurity and SES. Food insecurity was evaluated by endorsement of the statement “I don’t always have enough money to buy the food I need”. SES was assessed by the Hollingshead Index of Social Status , a weighted average of years of education, current or longest held occupation, and total household income of the participant.The stress variable consisted of the Perceived Stress Scale , a widely-used, 10-item, self report instrument that evaluates how stressful the respondent found situations in the past month. We categorized stress as high when PSS-10 scores were in the top tertile , and low when PSS-10 scores were in the bottom two tertiles, similar to previous research in PLWH. Following methods described by Troxel et al., 2003, each of the four indicators was dichotomized into “0” or “1” using the top or bottom 20-40% of the sample distribution. Our TES composite was the sum of the dichotomous values into one score ranging from 0-4 to represent a cumulative index of adverse experiences related to trauma, economic hardship, andstress. In the overall cohort, 32% had a score of 0, 30% had a score of 1, 23% had a score of 2, 11% had a score of 3, and 4% had a score of 4 on the TES composite. Figure 1 shows the distribution of TES by HIV status group.Participants completed a standardized, comprehensive neurocognitive battery including tests of executive function, learning, memory , working memory, verbal fluency,cannabis grow equipment speed of information processing, and complex motor skills. The cognitive battery has been described in full detail previously. Raw scores for each test were converted to T-scores adjusting for demographic characteristics and practice-effects when appropriate. Global and domain-specific continuous T-scores were used in our analyses.
All participants completed a modified version of the Activities of Daily Living Scale , a self-report measure used to assess an individual’s level of independent functioning in a range of daily activities. Participants rate their current and best level of functioning on 16 basic and instrumental everyday activities. For the current study, the summed total of domains on which declines were reported in current versus past functioning over the 16 ADLs was the everyday function outcome of interest.Prior to conducting primary analyses, independent samples t-tests and Chi-square tests were used to compare HIV status groups on demographic, psychiatric, substance use, and clinical variables. Any variables that differed between the HIV+ and HIV groups at p <.1 were added as covariates when analyzing the relationship between TES and cognitive/functional outcomes. Thus, we included gender, ethnicity, years of education, lifetime MDD, lifetime substance use disorder , lifetime alcohol use , and lifetime cannabis use in the models for cognition. We did not include current MDD as a covariate due to its low prevalence. For functional outcomes, we additionally included global neurocognitive impairment as a covariate. For PLWH-only models, any HIV disease characteristics that related to global cognition or ADL declines at p <.1 in univariable analyses were added as covariates. For our models in which a cognitive domain in PLWH wasthe outcome variable, current CD4 count was included as an additional covariate, given that it was associated with global cognition at p <.1 in univariable analyses. For our model in which a functional outcome in PLWH was the outcome variable, estimated duration of HIV infection was included as an additional covariate, given that it was associated with ADL declines at p <.1 in univariable analyses. We used multi-variable linear regression analyses to examine the independent and interactive effects of the TES composite and HIV status on cognitive function and declines in activities of daily living.
Separate univariable models were run for each of the seven cognitive domains and global cognition, and alpha was set at 0.006. We pursued multi-variable analyses only for those cognitive domains that showed a significant relationship with TES in univariable models, and in multi-variable analyses, alpha was set at 0.017 , based on the number cognitive domains tested. Effect sizes for regression analyses are presented as estimated regression coefficients in the results section. Post-hoc analyses examined how the components of our TES composite score correlated with each other in PLWH with Spearman’s rho correlations for continuous variables and Cohen’s d for dichotomous variables. We used Bonferroni corrections for multiple comparisons with alpha set at 0.008 for each comparison of two TES components. We used continuous and not dichotomous versions of our trauma, SES, and stress variables in post-hoc analyses to more precisely examine the contribution of each variable by utilizing the full range of variability in each of the scores. We also examined how the individual components of TES related to the cognitive and functional outcomes in PLWH using Cohen’s d for dichotomous variables , Pearson’s correlations for continuous variables approximating a normal distribution , and Spearman’s rho correlations for non-normally distributed continuous variables. To adjust for multiple comparisons, alpha was set based on the number of outcomes for each TES component: 0.013. In PLWH, elevated composite TES scores related to worse executive function, learning, and working memory performance, as well as worse daily functional abilities. The impact of these common traumatic and stressful experiences in PLWH may help to explain the high rates of mild neurocognitive and functional impairment observed in this population.
When individual components of TES were examined, food insecurity and stress were closely related to ADL declines, while TES components had overall small and non-significant relationships with cognitive domains of executive function, learning,vertical grow system and working memory. While mechanisms underlying the associations among TES and cognitive and everyday functioning are unclear, one possibility for the relation with lower cognitive and everyday functioning among PLWH is the combined effects of multiple adverse experiences and HIV on chronic immune dysregulation and inflammation. Based on our findings, we cannot definitively state that the TES-cognition relationship differs between the HIV+ and HIV- groups because we only observed additive main effects of HIV and TES and not an interaction on global cognition in our whole sample model. However, our HIV-stratified results suggest an interaction given that we saw a significant relationship between TES and domain-specific cognitive performance in the HIV+ group but not in the HIV- group. A larger sample may clarify whether HIV+ and HIV groups differ in the association between TES and cognitive function. Given the lower rates of trauma, food insecurity, stress, and less low SES in the HIV- group, we have a limited ability to assess the relation between these adverse experiences and cognitive and functional outcomes in those without HIV. Our findings suggest that TES is especially deleterious for cognitive and everyday functioning among PLWH given that TES remained a significant predictor even when controlling for demographic, educational, substance use, psychiatric, and HIV disease characteristics. Our post-hoc analyses revealed that, among PLWH, the individual components of our TES composite had small correlations with each other, indicating that trauma, economic hardship, and stress captured distinct but overlapping experiences. Furthermore, our post-hoc analyses showed that the correlations between the individual components of our TES composite and our outcome variables ranged broadly from small to moderate, suggesting that our findings are driven by the combination of these variables acting cumulatively to negatively impact everyday cognition and functional independence. Our results, which found that elevated TES composite scores are related to difficulties in executive functioning, learning, and working memory, are consistent with previous research that identified executive functioning and learning/memory domains as predominant areas of cognitive deficit in HIV. Given these findings, it is possible that trauma, economic hardship, and stress contribute to the worse neurocognitive functioning and the presence of mild neurocognitive impairment in HIV, which is prevalent in about 45% of PLWH.
In addition, our study confirms and extends previous research, which found a relationship between stressful life events and neuropsychological performance in men living with HIV, but not in men without HIV. Not only did we confirm this relationship, but we found that other socio-environmental factors, such as economic hardship, significantly influence this relationship in a sample of men and women living with HIV. These findings have clear clinical utility for PLWH’s overall healthcare. Specifically, these findings point toward screenings for adverse experiences. These screenings may allow for directed, comprehensive, services and resources, provided with cultural humility, that address social and structural factors. Such screenings and services may help to break the cycle of exposure to chronically stressful and traumatic contexts that may play a role in cognitive and functional impairment. Adversity assessments may also help to identify those who require additional screening for HIV-associated cognitive impairment. Our sample of participants without HIV reported a limited amount of trauma, economic hardship, and stress, which contributed to a restricted TES composite range. This restricted range may have contributed to the lack of relationship observed between our predictors and outcomes in this group. Thus, we have limited evidence to claim that trauma, economic hardship, and stress are unrelated to cognition and everyday functioning in individuals without HIV. There were a number of strengths in our study. First, we were able to identify significant effects of trauma, economic hardship, and stress on three cognitive domains and everyday functioning in a medium-sized sample of PLWH and compare these effects to those seen in a HIV- group. Second, our study utilized a comprehensive neuropsychological battery to assess cognitive functioning, which used multiple tests to tap seven domains of cognition. Finally, our study controlled for many more traditional predictors of cognitive and functional outcomes in PLWH than previous studies. Even when controlling for these covariates, results remained significant, demonstrating a unique and important contribution of adversity to these outcomes in PLWH. Our study also had several limitations. By nature, the cross-sectional design precludes detection of casual inference from the observed relationship of trauma, economic hardship, and stress with neurocognitive and everyday functioning in HIV. We also cannot rule out the possibility of causality in the opposite direction, such that worse neurocognitive and everyday function contribute to risk for trauma, economic hardship, and stress. Longitudinal studies, which are planned, are necessary to expand our understanding and explore the direction of effects between these factors. Our measures of trauma, stress, and economic hardship, were temporally limited to assessment of recent traumatic events , recent perceived stress , SES , and food insecurity , and did not capture cumulative stressors over the lifetime. With these time-frame constraints, our study lacked indicators of early life stress such as childhood trauma, which has been shown to have an interactive effect with HIV on neuropsychological functioning and structural morphology of the brain. Our trauma scale consisted of five items from the WHI Life Events Scale and has not been psychometrically validated as a measure of traumatic events. To better capture trauma, the 10-item Brief Trauma Questionnaire , which assesses type and severity of traumatic event and the 20-item PTSD Checklist for DSM-5 , which captures severity of PTSD symptoms, should be employed in future studies. Moreover, our study did not assess experiences of stigma and discrimination, a form of adversity that can act as a psychosocial stressor. Many PLWH experience discrimination due to their HIV or AIDS status, and/or the intersection of other identities such as sexual orientation, race/ethnicity, gender identity, and/or socioeconomic position, and these common experiences relate to worse health outcomes To the best of our knowledge this is the first study to examine the combined relationship of adverse social, structural, and psychological factors such as trauma, economic hardship, and stress concurrently with HIV on neurocognitive and everyday functioning outcomes. Given that there are high rates of sexual and physical abuse, trauma, and poverty among those living with HIV, the impact of these acute and chronic experiences should be a research priority with high clinical relevance, particularly in a population that often experiences compromised neurocognitive and immunological functioning. Clinically, assessing and addressing traumatic, stressful, and other adverse events in holistic and culturally-informed ways should be a part of standard HIV care. Future research should investigate the impact of trauma, economic hardship, and stress on the confluence of inflammation, immune dysregulation, and associated neural alterations in PLWH.