Stella E. Panos

Differential predictors of medication adherence in HIV: findings from a sample of African American and Caucasian HIV-positive drug-using adults.

Modest or even occasional nonadherence to combined antiretroviral therapy (cART) can result in adverse clinical outcomes. African Americans demonstrate lower rates of adherence than Caucasians or Latinos. Identifying factors that influence medication adherence among African Americans is a critical step toward reducing HIV/AIDS disease progression and mortality. In a sample of 181 African American (n=144) and Caucasian (n=37) HIV-positive drug-using individuals [age (M=42.31; SD=6.6) education (M=13.41; SD=2.1)], we examined the influence of baseline drug use, literacy, neurocognition, depression, treatment-specific social support, and patient satisfaction with health care provider on medication adherence averaged over the course of 6 months (study dates 2002-2006). Our findings suggest differential baseline predictors of medication adherence for African Americans and Caucasians, such that patient satisfaction with provider was the strongest predictor of follow-up medication adherence for African Americans whereas for Caucasians depressive symptoms and treatment-specific social support were predictive of medication adherence (after controlling for duration of drug use).

The aggregate effects of multiple comorbid risk factors on cognition among HIV-infected individuals.

This study developed and then cross-validated a novel weighting algorithm based on multiple comorbid risk factors (stimulant use, vascular disease, hepatitis C, HIV disease severity, cognitive reserve) to predict cognitive functioning among 366 HIV+ adults. The resultant “risk severity score” was used to differentially weight, as a function of age, the impact and magnitude of multiple risk factors on cognition. Among older adults (≥50 years) the risk severity index was differentially predictive of learning/memory and verbal fluency, whereas among younger adults it was linked to working memory and executive function. Cognitive reserve was found to be the most robust predictor of neurocognition.

The Role of HIV Infection, Cognition, and Depression in Risky Decision-Making

The authors examined the impact of HIV, cognitive dysfunction, and depression on decision-making. HIV+ (N=100) and HIV- (N=26) participants were administered a comprehensive neuropsychological battery, a modified version of the Iowa Gambling Task, and a measure of depressive symptoms. HIV+ participants demonstrated more difficulties in learning the gambling task than did HIV- participants. Executive functioning and depression emerged as strong predictors of gambling task performance. Depression partially mediated the relationship between executive functioning and gambling performance. Our findings suggest that HIV infection, executive dysfunction, and depression place individuals at risk for poor decision-making.

The impact of neurobehavioral features on medication adherence in HIV: Evidence from longitudinal models

Effective antiretroviral therapy has led to substantial improvements in health-related outcomes among individuals with HIV. Despite advances in HIV pharmacotherapy, suboptimal medication adherence remains a significant barrier to successful treatment. Although several factors have been associated with medication adherence in the extant literature, study assessing the effects of some of the neurobehavioral features specific to HIV has been limited. Moreover, although there is a growing body of literature measuring medication adherence in HIV prospectively, few employ advanced statistical methodologies suited to handle advanced models with multiple predictors that would strengthen our understanding of medication adherence trajectories in HIV. This study sought to integrate traditionally assessed predictors of medication adherence with neurobehavioral features of HIV in a longitudinal study of medication adherence to combined antiretroviral therapy (cART). The current study used multilevel modeling to examine a wide arrangement of categories of factors – demographic, medication related, psychosocial, and neurobehavioral – on medication adherence. The sample consisted of 235 HIV+ individuals whose medication adherence was monitored over the course of six months using electronic monitoring devices. After controlling for the effects of demographic, medication, and psychosocial factors, neurobehavioral features added predictive validity to the model. In the final model, simultaneously controlling for the effects of each of the predictors within all the categories, age, self-efficacy, executive functioning, apathy, and frequency of stimulant use emerged as unique individual predictors of average medication adherence across the 6-month study. Self-efficacy and irritability predicted changes in medication adherence over time. Adherence behavior is multidetermined. Adequate assessment of these factors, combined with timely intervention, appears to be warranted in order to boost adherence rates.

Basal ganglia structures differentially contribute to verbal fluency: Evidence from Human Immunodeficiency Virus (HIV)-infected adults

BACKGROUND The basal ganglia (BG) are involved in executive language functions (i.e., verbal fluency) through their connections with cortical structures. The caudate and putamen receive separate inputs from prefrontal and premotor cortices, and may differentially contribute to verbal fluency performance. We examined BG integrity in relation to lexico-semantic verbal fluency performance among older HIV infected adults. METHOD 20 older (50+ years) HIV+ adults underwent MRI and were administered measures of semantic and phonemic fluency. BG (caudate, putamen) regions of interest were extracted. RESULTS Performance on phonemic word generation significantly predicted caudate volume, whereas performance on phonemic switching predicted putamen volume. CONCLUSIONS These findings suggest a double dissociation of BG involvement in verbal fluency tasks with the caudate subserving word generation and the putamen associated with switching. As such, verbal fluency tasks appear to be selective to BG function.

Apolipoprotein-E genotype and human immunodeficiency virus-associated neurocognitive disorder: the modulating effects of older age and disease severity

BACKGROUND The apolipoprotein-E (APOE) ε4 allele is a risk factor for vascular dementia and Alzheimers disease. Recent studies are equivocal with regards to whether or not the ε4 allele confers increased risk for the development of human immunodeficiency virus (HIV)-associated neurocognitive disorder (HAND), but suggest that age and/or disease severity may be modulating factors. The aim of this study was to assess the interactions and contributions of APOE genotype, age, and HIV disease severity as risk factors for HAND in HIV-infected adults. METHODS Participants were 259 HIV-positive individuals who underwent APOE genotyping, a standardized neurological evaluation, a comprehensive neuropsychological evaluation, and laboratory testing. RESULTS Older ε4 carriers showed a higher frequency of HAND compared with age-matched non-ε4 carriers. Analysis by discrete neurocognitive domain revealed that advanced age modulated the effect of the ε4 allele, such that older ε4 allele carriers showed reduced executive functioning and information processing speed. Exploratory analyses assessing the relationship between ε4 and disease severity in the overall sample revealed that disease severity modulated the effect of the ε4 allele on cognition. Lower absolute CD4+ cell count among ε4 allele carriers was associated with poorer working memory ability. CONCLUSION Advancing age and degree of immunosuppression may influence the association between APOE ε4 allele status and HAND. These two factors need to be taken into account in future research.

A deconstruction of gambling task performance among HIV+ individuals: the differential contributions of problem solving and risk taking.

This study sought to deconstruct gambling task (GT) performance among HIV+ individuals (N = 143) and is intended to capture other cognitive features of task performance (i.e., problem solving and strategy preference). Consistent with our hypotheses, cluster analysis identified three GT groups: a safe/advantageous (AS) strategy group, a risky/disadvantageous (RS) strategy group, and a novel third group who failed to develop a strategy (NS). The NS group performed worst on global neuropsychological performance, processing speed, and executive function. Our results support a novel measure of GT task performance and suggest that failure to develop/implement a strategy reflects cognitive dysfunction.

Mild test anxiety influences neurocognitive performance among African Americans and European Americans: identifying interfering and facilitating sources.

The current study examined ethnic/racial differences in test-related anxiety and its relationship to neurocognitive performance in a community sample of African American (n = 40) and European American (n = 36) adults. The authors hypothesized the following: (a) Test-anxiety related to negative performance evaluation would be associated with lower neurocognitive performance, whereas anxiety unrelated to negative evaluation would be associated with higher neurocognitive performance. (b) African American participants would report higher levels of anxiety about negative performance evaluation than European Americans. (c) European Americans would report higher levels of anxiety unrelated to negative performance evaluation. The first two hypotheses were supported: Ethnic/racial differences in test-taking anxiety emerged such that African Americans reported significantly higher levels of negative performance evaluation, which was associated with lower cognitive performance. The third hypothesis was not supported: African Americans and European Americans reported similar levels of test-anxiety unrelated to negative evaluation.

Past Stimulant Abuse is Associated with Reduced Basal Ganglia and Hippocampal Integrity in Older HIV+ Adults: A Diffusion Tensor Imaging Study

Human Immunodeficiency Virus (HIV) and current stimulant abuse have both been shown to damage basal ganglia and hippocampus. While the effects of current stimulant abuse on neurological functioning is well- documented, whether residual damage can be detected in patients with a distant history of past stimulant abuse/ dependence remains to be understood. Given that past stimulant abuse is common among HIV-infected individuals; this is a question of considerable clinical significance. The present study employed Diffusion Tensor Imaging (DTI) and structural MRI to examine brain integrity (as measured by FA and MD) and volume in the basal ganglia (BG) and hippocampus among older HIV-infected adults with histories of stimulant abuse. Lower fractional anisotropy and greater diffusivity (representative of microstructural breakdown) in basal ganglia and hippocampal structures were documented among former stimulant abusers compared to stimulant-naive individuals. Length of abstinence was also associated with BG integrity, such that those with shorter abstinence periods demonstrated greater MD of the BG. Our findings suggest that past stimulant abuse is associated with neurological dysfunction, though this improves with increasing abstinence.

Neurocognition and Medication Adherence in HIV-Infected Adults

Pharmacological advances in the treatment of HIV infection have transformed what was once a terminal illness into a chronic illness. Although an increasing number of patients are being placed on antiretroviral therapy, poor adherence to treatment remains one of the leading causes of treatment failure. As such, research assessing factors that predict medication adherence to antiretroviral therapy is highly important from a public health perspective. This chapter will focus on the relationship between cognition and medication adherence among HIV-infected adults, with special emphasis on older HIV+ adults, one of the fasting growing subgroups in the HIV-infected populace. The chapter is intended to provide a broad overview of neuropsychological factors associated with medication adherence to antiretroviral therapy. We will begin with a brief review of some of the many methodological complexities important to consider in the study of medication adherence and cognition. The balance of the chapter will focus on key neurocognitive, psychiatric (including substance use), and psychosocial factors that are related to medication adherence in the HIV population.