Neurobehavioral HIV medicine最新文献

Pathologic stress (distress) disturbs immune, cardiovascular, metabolic, and behavioral homeostasis. Individuals living with HIV and those at risk are vulnerable to stress disorders. Corticotropin-releasing hormone (CRH) is critical in neuroendocrine immune regulation. CRH, a neuropeptide, is distributed in the central and peripheral nervous systems and acts principally on CRH receptor type 1 (CRHR1). CRH in the brain modulates neuropsychiatric disorders. CRH and stress modulation of immunity is two-pronged; there is a direct action on hypothalamic-pituitary-adrenal secretion of glucocorticoids and through immune organ sympathetic innervation. CRH is a central and systemic proinflammatory cytokine. Glucocorticoids and their receptors have gene regulatory actions on viral replication and cause central and systemic immune suppression. CRH and stress activation contributes to central nervous system (CNS) viral entry important in HIV-associated neurocognitive disorders and HIV-associated dementia. CNS CRH overproduction short-circuits reward, executive, and emotional control, leading to addiction, cognitive impairment, and psychiatric comorbidity. CRHR1 is an important therapeutic target for medication development. CRHR1 antagonist clinical trials have focused on psychiatric disorders with little attention paid to neuroendocrine immune disorders. Studies of those with HIV and those at risk show that concurrent stress-related disorders contribute to higher morbidity and mortality; stress-related conditions, addiction, immune dysfunction, and comorbid psychiatric illness all increase HIV transmission. Neuropsychiatric disease, chronic inflammation, and substance abuse are endemic, and chronic distress is a pathologic factor. It is being understood that stress and CRH are fundamental to neuroendocrine immunity; therapeutic interventions with existing and novel agents hold promise for restoring homeostasis, reducing morbidity and mortality for those with HIV and possibly reducing future disease transmission.

Medication adherence in persons treated for human immunodeficiency virus (HIV) continues to be an important focus for intervention. While high levels of adherence are required for good clinical outcomes, research shows many patients do not achieve these levels. Despite multiple interventions to improve adherence, most require multiple sessions delivered by trained clinicians. Cost and lack of trained personnel limit the availability of these interventions. Alternatives to clinician-delivered interventions are interventions provided via electronic devices (eg, personal/tablet computers and smartphones). Modern technology allows devices to provide tailoring of content to patient characteristics and learning needs, and to be excellent platforms to deliver multimedia teaching content. The intervention reported drew on research on health literacy in persons with HIV and the relation of health literacy to medication adherence in persons treated for HIV to develop an electronically delivered application. Using the Information-Motivation-Behavioral Skills model as a conceptual framework for understanding patients' information needs, a computer-delivered intervention was developed, its usability and acceptability was assessed, and medication adherence in 118 patients for 1 month before and after they completed the intervention was evaluated. Changes in participant adherence were evaluated in sequential models with progressively lower levels of baseline medication adherence. Results show that although changes in adherence in the entire sample only approached statistical significance, individuals with adherence less than 95% showed significant increases in adherence over time. Participants' self-reported knowledge and behavioral skills increased over the course of the study. Their change in information predicted their post-intervention adherence, suggesting a link between the intervention's effects and outcomes. A computer-delivered intervention targeting HIV-related health literacy may thus be a useful strategy for improving patient adherence.

Although the prevalence of neurocognitive disturbances among individuals with HIV has decreased in recent years, rates of impairment still remain high. This review presents findings from comorbid conditions that may contribute to further neurocognitive impairments in this already vulnerable population. We will focus on three co-factors that have received substantial attention in the neuroAIDS literature: drug use, hepatitis C co-infection (HCV), and aging. All three conditions commonly co-occur with HIV and likely interact with HIV in complex ways. Collectively, the extant literature suggests that drug use, HCV, and aging serve to worsen the neurocognitive profile of HIV through several overlapping mechanisms. A better understanding of how specific comorbidities interact with HIV may reveal specific phenotypes of HIV-associated neurocognitive disorder that may aid in the development of more targeted behavioral and pharmacological treatment efforts.

Mannose binding lectin (MBL) activates complement pathway that leads to pathogen opsonization and phagocytosis. MBL deficiency is linked to HIV transmission and disease progression. We sought to determine the role of MBL in HIV encephalitis (HIVE) by evaluating its presence and distribution in the HIV-1-infected brain and by assessing its association with monocyte chemoattractant protein-1 (MCP-1) expression. This retrospective study utilized archived post-mortem brain tissues obtained from 35 individuals enrolled in a longitudinal study as part of the California NeuroAIDS Tissue Network. MBL, MCP-1 and brain cell markers in post-mortem brain tissues with or without HIVE were evaluated using immunocytochemistry, immunofluorescence, confocal microscopy, and western blots. MBL was expressed in neurons, astrocytes, microglia, and oligodendrocytes of the frontal cortex of the HIV-1-infected brain. Overall, there were 30% to 40% more MBL-positive brain cells in HIVE vs non-HIVE cases (P = 0.01, paired t-test). Specifically, there was an increased MBL expression in the neuronal axons of HIVE cases. Also, western blots showed 3- to 4-fold higher levels of 78 kD MBL trimers in HIVE vs non-HIVE cases. This MBL-HIVE link was further confirmed by MBL associated higher MCP-1 expression in HIVE vs non-HIVE cases. HIV negative healthy individuals and normal or the gp120 transgenic mice did not show any differential MBL expression. Increased MBL expression in the major brain cell types, specifically in the neuronal axons of HIVE brain, and MBL associated higher MCP-1 expression in HIVE suggest that MBL could cause neuroinflammation and neuronal injury through MBL complement activation pathway.

Background: A substantial number of Spanish-speaking individuals from Mexico and Central America are now living in the United States. These individuals are at heightened risk for HIV infection and, due to late diagnosis and limited resources, for HIV-associated neurocognitive disorders (HAND). Early detection is key, yet adequate methods for detecting HAND in Spanish speakers, especially in resource-poor areas, remains problematic. Therefore, it is necessary to identify accurate yet efficient neurocognitive screening tools that are appropriate for use in resource-limited AIDS clinics serving Spanish-speaking patients.

Methods: Twenty-one Spanish-speaking, HIV-positive adults who migrated from Mexico or Central America underwent neuromedical and neurocognitive evaluation in Spanish. The concordance of three neurocognitive screening measures (the HIV Dementia Scale [HDS], the Mini-Mental State Examination [MMSE], and the NEUROPSI) with a comprehensive neuropsychological battery was examined. In addition, accuracy in detecting neurocognitive impairment using standard and alternative cutoff scores was examined.

Results: The HDS and the NEUROPSI showed high correlation with the comprehensive neuropsychological battery. The HDS and the NEUROPSI also had the highest sensitivity (67% and 75%, respectively) and specificity (50% and 38%, respectively). Both measures also showed greater sensitivity than the MMSE to very mild forms of HAND.

Conclusion: In this small sample of HIV-positive Spanish speakers from Mexico and Central America living in the United States, the HDS and the NEUROPSI demonstrated reasonable accuracy in detecting neurocognitive impairment, while the MMSE demonstrated very poor accuracy. The HDS and the NEUROPSI were equally sensitive in detecting mild HAND. Continued test development is required to capture this disorder, especially in resource-limited settings.

The frequency of mood and anxiety disorders is elevated among individuals with a history of intravenous drug abuse and among those with human immunodeficiency virus (HIV), and these disorders are associated with continued substance use despite treatment. The present study examined rates of mood and anxiety disorders, and recent heroin use, among HIV-infected and HIV-noninfected patients receiving methadone maintenance therapy. Participants were 160 (80 HIV-infected, 80 HIV-noninfected) methadone patients. Clinician-administered, semistructured interviews were used to identify unipolar and bipolar depression, and four major anxiety disorders (panic disorder with agoraphobia [PDA], generalized anxiety disorder [GAD], post-traumatic stress disorder [PTSD], and social anxiety disorder [SAD]). Toxicology screens and self-reporting were used to assess heroin, cocaine, marijuana, and alcohol use over the past month. The entire sample met criteria for at least one psychiatric disorder other than substance dependence. Substantial proportions of participants met criteria for major depressive disorder (55.6%), bipolar I, bipolar II, or cyclothymia (6.4%), PDA (34.4%), GAD (22.5%), SAD (16.9%), and PTSD (34.4%). A greater proportion of HIV-infected participants met criteria for SAD (χ² = 5.03), and a greater proportion of HIV-noninfected participants met criteria for GAD (χ² = 5.39, P < 0.01). About 14% of participants continued to use heroin over the past month, a significantly greater proportion of whom were HIV-infected. In adjusted analyses, none of the mood or anxiety disorders emerged as significant predictors of recent heroin use, but being HIV-infected did. This study highlights the high rate of psychopathology and continued heroin use despite substance abuse treatment, and underscores the need for interventions that help mitigate these problems among methadone patients.

PURPOSE: Perinatally HIV-infected children, who are increasingly aging into adolescence and early adulthood, have significant rates of psychiatric co-morbidities, some of which are treated with second-generation antipsychotics (SGAs). SGAs have been associated with elevated total cholesterol (TC) in youth, but no studies have examined this association in perinatally HIV-infected youth. This study examined changes in TC levels of youth with perinatally acquired HIV infection and co-morbid psychiatric conditions treated with SGAs. PATIENTS AND METHODS: Long-term changes in TC levels were examined using data from the US multisite prospective Pediatric AIDS Clinical Trials Group 219C cohort study. The change in TC levels from baseline to 12 months after initiating SGA use was compared between 52 SGA-exposed and 148 matched SGA-unexposed perinatally HIV-infected youth, using generalized estimating equation models adjusting for other covariates. The prevalence and time to incident hypercholesterolemia were also compared between these 2 groups. RESULTS: After adjustment for confounders, 52 youth with prescriptions for SGAs had a larger increase in TC levels than 148 matched youth without antipsychotic prescriptions (mean difference = 9 mg/dL, z = 1.96, df = 1, P = 0.0496). Among youth with TC below 220 mg/dL at baseline, 27% of SGA-exposed youth developed hypercholesterolemia (defined as two consecutive TC measurements ≥220 mg/dL), compared with 13% of SGA-unexposed patients (Fisher's exact test, P = 0.046). CONCLUSIONS: Caution should be used in prescribing SGAs to perinatally HIV-infected youth with psychiatric co-morbidities due to increased risk of hypercholesterolemia. Patients should be monitored, and alternative evidence-based treatments considered when available.

The catechol-O-methyltransferease (COMT) Val allele has been linked to executive dysfunction among healthy individuals. The nature of this relationship is unknown in the context of HIV infection and/or methamphetamine (METH) dependence, two conditions that can alter dopaminergic system functioning. We sought to determine if the putative relationship between COMT and executive dysfunction could be observed among individuals with and without HIV-infection and/or METH dependence, and to explore the specificity of this relationship by examining other cognitive domains. Utilizing an existing cohort of 229 men with and without HIV infection and/or METH dependence we found that Met/Met carriers within the HIV-only and control groups, displayed better executive functioning compared to Val/Val and Val/Met carriers. However, this effect was attenuated in the METH-only and comorbid (ie, HIV+/METH+) groups. Examination of other neurocognitive domains were not consistent with effects found for executive functioning. Results support the presumed neuroprotective effect of Met/Met genotype on executive functioning among HIV-only and control groups. Among METH-only and comorbid groups, the slower rate of dopamine clearance conferred by the Met/Met genotype may increase the risk of adverse effects of METH, resulting in comparable executive dysfunction to that of Val allele carriers.

Injection drug users engage in behaviors that increase the spread of human immunodeficiency virus (HIV) and other infectious diseases. Although methadone maintenance (MM) is highly effective in decreasing heroin use and the spread of HIV, polydrug use, especially the combined use of cocaine and alcohol, is common in MM patients. Alcohol use is independently associated with HIV risk behaviors, and the effects of alcohol use on risk behaviors may vary by gender. This study evaluated the effects of recent heavy alcohol use and gender with respect to HIV risk behaviors in 118 cocaine-abusing methadone patients. Both lifetime and past month injection and sexual risk behaviors were examined. Recent heavy drinkers (n = 46) were more likely to be male than nonheavy drinkers (n = 72). Recent heavy drinkers reported more risky sexual behaviors over their lifetimes than nonheavy drinkers. Gender effects were also present for lifetime risk behaviors, with females demonstrating more sexual and injection risk behaviors than men. In terms of recent injection risk behaviors, there was a significant alcohol use by gender effect. Heavy drinking females reported significantly more drug-sharing behaviors and less frequent needle cleaning than nonheavy drinking females. Recent sexual behaviors did not differ based on alcohol use status or gender. These findings may inform HIV prevention strategies in cocaine-abusing MM patients, and they suggest that cocaine-abusing women who drink heavily are a particularly high risk group who should be counseled about risky injection drug use practices.