Drenna Waldrop-Valverde

Neuropsychological deficits in human immunodeficiency virus type 1 clade C-seropositive adults from South India

Most studies of cognitive functioning in human immunodeficiency virus type 1 (HIV-1)-seropositive (HIV-1+) subjects have been done in the United States and Europe, where clade B infections predominate. However, in other parts of the world such as South India, where clade C HIV is most common, the prevalence of HIV-1 is increasing. Standardized neuropsychological tests were used to assess cognitive functioning in a sample of 119 adults infected with clade C HIV-1 who were not on antiretroviral medications. The subjects did not have neurological or psychiatric illness and were functioning adequately. Neuropsychological test performance was compared with gender-, age-, and education-matched normative data derived from a sample of 540 healthy volunteers and a matched cohort of 126 healthy, HIV-1-seronegative individuals. Among the seropositive subjects, 60.5% had mild to moderate cognitive deficits characterized by deficits in the domains of fluency, working memory, and learning and memory. None of the subjects had severe cognitive deficits. The HIV-1+ sample was classified into groups according to the level of immune suppression as defined by CD4 count (<200, 201–499, and >500 cells/mm3) and viral load (<5000, 5001–30,000, 30,001–99,999, 100,000–1,000,000, and >1,000,001 copies). Although the most immunosuppressed group (CD4 count <200 cells/mm3 or viral load >1,000,001 copies) was small, their rate of impairment in visual working memory was greater when compared to groups with better immune functioning. Mild to moderate cognitive deficits can be identified on standardized neuropsychological tests in clade C-infected HIV-1+ adults who do not have any clinically identifiable functional impairment. The prevalence of cognitive deficits is similar to that reported in antiretroviral treatment-naïve individuals infected with clade B virus in the western world.

Human immunodeficiency virus type 1 in the central nervous system leads to decreased dopamine in different regions of postmortem human brains

Human immunodeficiency virus type 1 (HIV-1) invades the central nervous system (CNS) shortly after infection and becomes localized in varying concentrations in different brain regions, the most vulnerable is the basal ganglia (BG). It is hypothesized that HIV-1-mediated neuropathogenesis involves degeneration of dopaminergic neurons in the substantia nigra and the loss of dopaminergic terminals in the BG, leading to deficits in the central dopaminergic activity, resulting in progressive impairment of neurocognitive and motor functions. In the era of highly active antiretroviral therapy (HAART), although the incidence of HIV-associated dementia (HAD) has decreased, the neurocognitive and neuropsychological deficits continue to persist after HAART. In this study, We investigated the impact of HIV-1 on dopaminergic activity with respect to concentrations of dopamine (DA) and homovanillic acid (HVA) in different regions of postmortem human brains of HIV-1negative and HIV-1+ individuals and their relationship to neurocognitive impairment. We found that in HIV-1+ as well as HIV-negative cases, dopamine and HVA concentrationsin ranged widely in different brain regions. In HIV-negative brain regions, the highest concentration of DA was found in putamen, caudate, substantia nigra, and the basal ganglia. In HIV-1+ cases, there was a significant decrease in DA levels in caudate nucleus, putamen, globus pallidus, and substantia nigra compared to that in HIV-negative cases. In HIV-1+ cases, a strong correlation was found between DA levels in substantia nigra and other brain regions. Concentration of HVA in HIV-negative cases was also highest in the regions containing high dopamine levels. However, no significant decrease in regional HVA levels was found in HIV-1+ cases. HIV-1 RNA load (nondetectable [ND] to log10 6.9 copies/g tissue) also ranged widely in the same brain regions of HIV-1+ cases. Interestingly, the brain regions having the highest HIV-1 RNA had the maximum decrease in DA levels. Age, gender, ethnicity, and postmortem interval were not correlated with decrease in DA levels. Profile of DA, HVA, and HIV-1 RNA levels in the brain regions of HIV-1+ individuals treated with HAART was similar to those not treated with HAART. A majority of HIV-1+ individuals had variable degrees of neurocognitive impairments, but no specific relationship was found between the regional DA content and severity of neurocognitive deficits. These findings suggest widespread deficits in dopamine in different brain regions of HIV-1-infected cases, and that these deficits may be the results of HIV-1-induced neurodegeneration in the subcortical regions of human brain.

Human immunodeficiency virus infection in the CNS and decreased dopamine availability: relationship with neuropsychological performance.

Human immunodeficiency virus (HIV-1) infection in the central nervous system (CNS) is associated with a wide range of neurological, cognitive, and behavioral problems. HIV-1 enters the brain soon after the initial infection and is distributed in varying concentrations in different regions with specific affinity to the subcortical regions, particularly the basal ganglia, causing neurodegeneration of dopaminergic regions and resulting in the decreased availability of dopamine (DA) in the CNS. Although there are numerous reports on HIV-1-associated neuropsychological (NP) impairment, there is a paucity of studies showing a direct relationship between the decreased availability of dopamine in different regions of postmortem brains of HIV-1-infected individuals and the level of performance in different NP functions during life. Dopamine is the key neurotransmitter in the brain and plays a regulatory role for motor and limbic functions. The purpose of the present study was to investigate the relationship between the decreased availability of dopamine found in the postmortem brain regions (fronto-cortical regions, basal ganglia, caudate, putamen, globus pallidus, and substantia nigra) of individuals with HIV/AIDS and the antemortem level of performance (assessed as T scores) in different NP functions. The relationship between HIV-1 RNA levels in different brain regions and the level of performance in different NP domains was also investigated. We found that although DA concentrations were 2–53% lower in the brain regions of HIV-1-infected, HAART-treated individuals, compared with HIV-negative controls, a 45% decrease in DA levels in the substantia nigra (SN) of HIV-1-infected individuals was significantly correlated with the low level of performance (T scores) in the speed of information processing, learning, memory, verbal fluency, and average T scores across domains. In case of homovanillic acid (HVA), the variable changes in different regions, including the substantia nigra, basal ganglia, caudate, and putamen (compared to that in the HIV-negative individuals), were significantly correlated with the level of performance (T scores) in motor functions, speed of information processing, and attention/working memory. HIVRNA levels in the frontal cortex, caudate, and GP were significantly inversely correlated with abstract/executive function, motor, learning, verbal fluency, and attention/working memory. No significant correlations were found between HIVRNA in other brain regions and NP performance. These findings suggest that the decreased availability of dopamine in the SN (the main site of DA synthesis in the CNS), and changes in the levels of HVA in different brain regions are, in part, related with the lower level of performance in some of the NP functions in individuals with HIV/AIDS.

Numeracy Skills Explain Racial Differences in HIV Medication Management

Racial disparities in HIV/AIDS are well established and efforts to understand key factors that may explain these differences are needed. Recent evidence suggests that health literacy may contribute to disparities in health behaviors among African American HIV patients. One component of health literacy, numeracy, is emerging as an important skill for successful self management of medications. We therefore tested whether numeracy mediated the effects of race on medication management among HIV seropositive patients. Results showed that poor management of a simulated HIV medication regimen among African Americans and women was mediated by lower numeracy. Poor medication self-management may be a significant root cause for health disparities in African Americans with HIV/AIDS. Whether African American women may be at particular risk requires further study. Interventions to improve HIV medication self-management through addressing numeracy skills may help to narrow the gap in health disparities among African Americans with HIV/AIDS.

Gender differences in medication management capacity in HIV infection: the role of health literacy and numeracy.

Health literacy is emerging as a key element for successful medication management and empirical support for the efficacy of numeracy in the health context is rising as well. Little is known, however, about their unique effects among women and men. Given the importance of accurate medication management for effective treatment of HIV, the relation of these variables to medication management needs to be assessed. We therefore tested the relation of health literacy (reading comprehension) and numeracy to one’s ability to manage a “mock” HIV regimen and whether men and women differed in these abilities. Results showed that women were less able than men to follow medication instructions and answer questions about the mock regimen. Numeracy mediated the relationship between gender and medication management. These findings highlight skills used in managing medication regimens and suggest avenues to target for identification and intervention in medication management among women and men with HIV.

Neurocognitive Aspects of Medication Adherence in HIV-Positive Injecting Drug Users

Cognitive deficits are associated with nonadherence to HIV medications. HIV-positive injecting drug users (IDUs) are at particular risk for nonadherence and cognitive barriers to adherence specific to this population should therefore be identified. The present study assessed the relation of three domains of cognitive functioning, executive functions, memory, and psychomotor speed, to self-reported antiretroviral adherence in a sample of HIV-positive IDUs. Depression, use of alcohol, heroin, cocaine/crack, or marijuana in the last week were also included in the models. Logistic regression analyses showed that only psychomotor slowing was significantly associated with nonadherence. Executive functions, memory, depression, and active alcohol and substance use were unrelated to adherence. No other studies to date have exclusively linked psychomotor slowing to nonadherence in HIV infection. Psychomotor slowing among our study sample was severe and suggests that when evident, such slowing may be a valuable determinant for antiretroviral adherence among IDUs.

Neurocognition, health-related reading literacy, and numeracy in medication management for HIV infection.

Successful medication management is an essential ingredient for effective treatment for HIV. Risk factors for poor medication adherence, including neurocognitive impairment and low health literacy, are common in HIV patients. To better understand the most salient risks for poor management of HIV medications, we tested the interrelation of neurocognitive functioning, reading literacy for health related information, and numeracy and their effect on self-management of a simulated HIV medication regimen. Cross-sectional data on 191 HIV-positive men and women recruited from HIV outpatient clinics in South Florida were collected. Exploratory factor analysis was conducted with literacy, numeracy, and neurocognitive scores and suggested that four factors were present representing executive skill, verbal memory, planning, and motor speed. Both the literacy and numeracy scores loaded on the executive factor. Adjusted analyses showed that executive and planning skills were significantly related to medication management. Findings suggest that patients must rely on higher order cognitive skills to successfully navigate medication self-management, and that efforts to simplify health information that merely lowers readability are likely to meet with limited success.

Health literacy: impact on the health of HIV-infected individuals.

Health literacy is known to affect vulnerable communities such as persons living with HIV/AIDS. The purpose of this review was to provide a current summary of research on the impact of health literacy on the health of persons living with HIV/AIDS and to address future areas of need. Contemporary studies focused on expanding the reach of health literacy in HIV/AIDS to retention in HIV care, use of technology for assessing and intervening to improve health literacy, and health literacy across the globe, for example. A number of studies did not find health literacy to explain health behaviors whereas other studies supported such a relationship. Future issues relevant to health literacy in HIV/AIDS include the aging of the HIV population and associated comorbidities, studies to understand the role of health literacy in specific populations affected by HIV/AIDS, and the continued need to refine the definition and measurement of health literacy.

Correlates of depression among HIV-positive women and men who inject drugs.

Introduction:Although depression is common among HIV-positive injection drug users (IDUs), little is known about differences between male and female HIV-positive IDUs. Methods:We used baseline data for 1126 HIV-positive IDUs from a behavioral intervention trial from 2001 through 2005 in 4 US cities. Using the Brief Symptom Inventory-18, scores indicating high risk for depression were calculated separately for men and women based on raw scores of 9 for women and 7 for men. We did separate logistic regressions for men and women to evaluate correlates of depression in 4 domains: sociodemographic, psychosocial, substance use, and sexual behaviors/attitudes. Results:Approximately one third of women and men met the criteria for being at high risk of depression. Women reported significantly more depressive symptoms than men. Correlates linked with depression for both genders included perceived functional limitation, greater negative feelings regarding condom use, lower social support, and lower sense of empowerment. Being physically abused as adults and being Hispanic were correlates specific to men. No unique correlate was identified for women. Discussion:Because of the high prevalence of depression among HIV-positive IDUs, caregivers should screen HIV-positive IDUs for depression and consider treatment for depression. Because of the similarities in correlates of depression among men and women, case finding and interventions for depression are likely to be similar for male and female HIV-positive IDUs.

Sexual risk reduction among Zambian couples

Zambia has over 1 million HIV infections nationwide and an urban prevalence rate of 23%. This study compared the impact of male involvement in multiple and single session risk reduction interventions among inconsistent condom users in Zambia and the role of serostatus among HIV-seropositive and serodiscordant couples. Couples (N=392) were randomised into intervention arms. Among inconsistent condom users at baseline (N=83), condom use increased in both conditions and this increase was maintained over a 12-month period. At 12 months, seronegative men in the multiple session condition increased sexual barrier (male and female condoms) use in comparison with those in the single session condition (F=16.13, p=0.001) while seropositive individuals increased sexual barrier use regardless of condition. Results illustrate the importance of both single and multiple session risk reduction counselling among seronegative men in serodiscordant couples in Zambia, and highlight the differing perception of risk between seropositive and serodiscordant persons.