Search

PARTICIPANTS: V. Valcour, B. Shir0mizu, C. Shikuma (University of Hawaii School of Medicine, Honolulu, HI). Medication Adherence and Clinical Outcomes Among Older Compared to Younger HIV-1 Seropositive Individuals. Few data exist concerning the effect of age on adherence to antiretroviral medication. Age-associated comorbid conditions, including alterations in hepatic and renal metabolism, are postulated to decrease an older persons ability to comply with a multiple drug regimens. An increased use of concomitant medications could also negatively effect compliance. While one study suggested an adherence rate as low as 28% for older HIV seropositive individuals, other sites suggest good adherence with similar rates and patterns of antiretroviral use among older compared to younger individuals. Pilot data also suggest older patients may require fewer changes in antiretroviral regimen and have as good or superior virologic control when compared to younger individuals (age 18-39). A group of HIV seropositive individuals fifty years of age and over (n=100) and a comparison seropositive group between 18-39 years of age (n=100) will be enrolled over 2 years to evaluate cognitive function at the University of Hawaii. Annual self-report of adherence is obtained through a structured questionnaire assessing adherence over the past 4 days and over the past month. Participants who miss any dose are considered < 100% compliant. Preliminary analysis suggests a similar percentage of older compared to younger individuals are 100% adherent to HAART (85% in the older group, 83% in the younger group). A larger sample size will allow confirmation of these findings and analysis of endpoints such as viral load suppression and immunological parameters. K. Goodkin, D. Asthana, P. Shapshak, M. Concha, F. Wilkie, I, Khamis, D. Lee, A. Ardila, R. Lecusay, P. Suarez, D. Rigg. W. Zheng, S. O'Mellan (University of Miami School of Medicine, Miami, FL). Neurocognitive Symptoms and Immunological and Virological Correlates in Older HIV-1 Seropositive Individuals. In a NIMH and NIA-funded study of the impact of age on cognitive impairment in HIV-1+ individuals, we have noted the symptoms of minor cognitive-motor disorder as more frequent in older than younger HIV-1+ individuals. The association of aging and HIV-1 serostatus with the CD4/CD8 ratio showed a significant effect of age and an age by HIV-1 serostatus interaction. The older HIV-1- group had a higher CD4/CD8 ratio than the younger HIV-1- group, while the difference between the older and younger seropositive groups was not statistically significant. On the CD8 cell count, a controlled model showed a statistically significant age by HIV-1 serostatus interaction. HIV-1+ individuals, as expected, had higher CD8 cell counts than HIV-1-individuals, regardless of age. In addition, older HIV-1+ individuals had a higher CD8 cell count than younger HIV-1 seropositive individuals. This suggests that the cytotoxic T lymphocyte subset of CD8+ T lymphocytes may have been increased and activated by exposure to a higher viral burden. However, an analysis of plasma viral load showed significantly lower load in the older group unaccounted for by antiretroviral medication adherence ratings. There is no one-to-one correlation between RNA load, live virus, and the viral proteins within virions and those free in plasma. Given the increase in CD8 cell count, this suggests that the activation of CD8 cells may be due to a differential production of viral gene products rather than whole virions. M. Neundorfer, C, Camp. M. Lee, M. Malone. J. Carr, M. Skrajner (Myers Research Institute, Beachwood, OH). A Cognitive Intervention for Persons Age 50 and Over with HIV: Pilot Results on Dementia Screening and Treatment Effects. The purpose of this study was to test the effectiveness of a cognitive intervention for ameliorating executive function deficits in adults positive for HIV who are age 50 or over. Subjects were screened for cognitive deficits with a primary emphasis on executive dysfunction. They were also screened for depression and anxiety, as well as past and current comorbidities, including drug and alcohol abuse. CD4 counts and viral loads were ~)btained from their clinical records. Ten subjects who met criteria for executive function deficits received the cognitive intervention. This intervention involved (a) the use of external aids to address deficits in memory and executive function, and (b) Spaced-Retrieval, a method of learning and retaining information over increasingly longer periods of time. Subjects identified personal therapy goals based on functional disabilities (e.g., forgetting appointments) and then met individually with the study therapist for up to 12 half-hour treatment sessions to achieve goal mastery (e.g., effective use of a calendar). Two months post-mastery, subjects were tested for mastery retention. Results will be presented as selected case studies, showing individual patterns of cognitive deficits from the screening, mood disorders, co-morbidities, pre-treatment functional disabilities, therapy goals, specific interventions, number of treatment sessions required to achieve mastery, and evidence of effectiveness and retention. Pilot results indicate that this cognitive intervention can compensate for cognitive deficits, thus helping older persons continue HIV care. A. Justice, K. McGinnis, J. Wagner, J. Conigliaro, L. Rabeneck (VA Pittsburgh Healthcare System, Pittsburgh, PA). Medical and NeuroPsychiatric Comorbidity in HIV Infection and Its Association with Patient Outcomes. Thanks to the development and dissemination of multi-drug, multi-class antiretroviral therapy, people with HIV infection are living longer. As a result of this extended life expectancy, and long-term drug toxicities, comorbid medical and neuropsychiatric conditions are likely to play an increasingly important role in determining survival and quality of like for people living with HIV infection. The Veterans Aging Cohort 3 Site Study enrolled 881 veterans from 3 HIV clinical care sites representing 85% of all veterans with HIV seen during this interval at these clinics. At the time of enrollment and approximately 12 months later, subjects completed questionnaires that included information on their health related quality of life (SF-12) and on comorbid medical and psychiatric conditions. The patients' primary medical provider also completed a questionnaire regarding medical and psychiatric conditions experienced by the patients. Laboratory and pharmacy data were also collected. We have now followed patients for an average of 2 years and have experienced 70 deaths. We will report the association of specific medical and neuro-psychiatric conditions to survival and quality of like in this cohort. DISCUSSANTS: D. Stoff (Center for Mental Health Research on AIDS, Bethesda, MD), N. Linsk (University of Illinois at Chicago, Chicago, IL). For most HIV-1 seropositive individuals in the United States, HIV-1 infection is now a chronic process. A multifaceted approach, common to caring for a geriatric individual, is required. Additionally, the advent of highly active antiretroviral therapy (HAART) has prolonged survival for individuals infected and is contributing to a larger population of older seropositive individuals. As the treatment of HIV-1 infection in the United States enters its third decade, research and clinical care must change to meet emerging needs as the causes of morbidity and mortality among the HIV-1 infected begin to coalesce with those of the general population. This is of paramount importance for neurocognitive function. Here, important aspects of clinical care, including antiretroviral medication adherence, immunological function and presence of medical comorbidities play a fundamental role in risk profiles and prevention strategies. This symposium is designed to address neurocognitive function in older HIV-1 seropositive individuals with particular emphasis on its impact in primary medical care.

Background: Efavirenz is a commonly used antiretroviral drug that causes neurologic side effects in more than 50% of patients.Objective: To characterize efavirenz-associated neurologic symptoms in a randomized, controlled study of initial antiretroviral treatment.Design: Substudy of a randomized, double-blind, controlled trial of combination antiretroviral regimens (A5095) that was performed between March 2001 and January 2002.Setting: Multicenter academic clinical trial units.Participants: HIV-infected patients who were initiating therapy in the context of a controlled trial.Measurements: Neuropsychological performance measures, including the Digit Symbol Substitution Test and the Trail Making Test (Parts A and B); symptom questionnaires; standardized assessments of sleep quality, anxiety, and depression; and efavirenz plasma concentrations.Results: Twenty of 303 (6.6%) enrolled participants prematurely discontinued the study. Neuropsychological performance improved in both groups over time without significant differences between patients who were receiving efavirenz and those who were not. The efavirenz group experienced more neurologic symptoms at week 1 (P < 0.001) but not at weeks 4, 12, or 24. A sleep index revealed that participants receiving efavirenz had more "bad dreams" during the first week of therapy (P = 0.038). No significant changes in anxiety or depressed mood were noted. Changes in efavirenz-associated neurologic symptoms were correlated to efavirenz plasma concentrations at week 1 but not at later time points. Twelve (6%) patients receiving efavirenz stopped taking the drug before the end of the study because of central nervous system symptoms.Limitations: Participant selection may have been biased in favor of patients with fewer psychiatric complications. The study design permitted substitution of a new drug in place of efavirenz in cases of treatment-limiting toxicity.Conclusions: In a large controlled trial, efavirenz use was associated with neurologic symptoms distinct from depression and anxiety that began early in therapy but resolved by week 4. Improvement in neuropsychological performance was comparable in patients who were receiving efavirenz and those who were not. [ABSTRACT FROM AUTHOR]

The point at which the experience of grief in response to bereavement becomes 'pathological' has been debated for many years without resolution. This article reviews the current status of this debate. The debate centers around the extent to which 'complicated grief' represents a truly unique pathological entity, when contrasted with major depressive disorder, posttraumatic stress disorder, and 'uncomplicated grief.' Significant research findings suggest it may be possible to distinguish grief from depressed as well as traumatic forms of distress, with acceptable reliability and validity. Yet, 'complicated grief' relates to both of these types of distress as well as to a unique aspect--separation distress. It is at the intersection of these types of distress with significant disruption of daily life functioning that we find the proposed diagnosis of 'complicated grief.' The question is whether this diagnosis should be designated at this time, and, if so, how. This article concludes in favor of a compromise position that the diagnosis should be incorporated into DSM-V but relegated to its Appendix B [disorders proposed for further study] due to the lack of clarity surrounding its diagnostic criteria. [ABSTRACT FROM AUTHOR]

Infection of the brain by HIV-1 often results in cognitivemotor disorders, the most severe form being HIV-1 associated dimentia (HAD). However, the etiology and pathogenesis of neuroAIDS at the molecular level is still not fully understood and controversial issues remain, including the significance of abortive infection and localized viral load. This paper proposes that quantitative comparison of HIV-1 proviral and RNAloads across the brain will clarify some of these issues. It was hypothesized that there are differences in ratios of multispliced and unspliced HIV RNA in different regions of brain by analogy with prior findings of brain regional differences in virus and strains of HIV-1. A competitive RT-PCR method was used to compare ratios of multispliced to unspliced HIV-1 RNA's across brain regions of one case with HAD. Statistical analysis results showed that data obtained by repeated assays for each RNA preparation were not significantly different. Significant differences were detected between specimens obtained from different regions of the brain. The ratio of MS/US RNA in the frontal lobe was significantly greater than in the basal ganglia, medial temporal lobe, and another site in the temporal lobe. It must be noted that our approach has been the analysis of macroscopic brain regions separated by several centimeters; future studies will analyze microscopic analysis of these brain regions. The current study was preformed to produce results on gross differences in neuroanatomical locations at cm distances. Future studies will be performed to compare different regions with microscopic anatomic specificity. [ABSTRACT FROM AUTHOR]

Objective: This study examines whether stressful negative life events and pessimism were associated with lower natural killer cell cytotoxicity (NKCC) and T cytotoxic/suppressor cell (CD8+CD3+) percentage in black women co-infected with human immunodeficiency virus Type 1 (HIV-1) and human papillomavirus (HPV), a viral initiator of cervical cancer.Method: Psychosocial interviews, immunological evaluations, and cervical swabs for HPV detection and subtyping were conducted on 36 HIV+ African-American, Haitian, and Caribbean women.Results: Greater pessimism was related to lower NKCC and cytotoxic/suppressor cells after controlling for presence/absence of HPV Types 16 or 18, behavioral/lifestyle factors, and subjective impact of negative life events.Conclusions: A pessimistic attitude may be associated with immune decrements, and possibly poorer control over HPV infection and increased risk for future promotion of cervical dysplasia to invasive cervical cancer in HIV+ minority women co-infected with HPV. [ABSTRACT FROM AUTHOR]

Objective: Previous research has demonstrated that a theoretical model including measures of life stressors, social support, and coping style significantly predicts psychological distress. This study tested plasma pyridoxine (vitamin B6) deficiency status as a predictor of overall psychological distress and specific mood states in this model, controlling for HIV-1 serostatus.Method: Subjects included HIV-1+ (N = 76) and HIV-1- (N = 58) recently bereaved homosexual men. At baseline, subjects completed a battery of psychosocial questionnaires, together with a physical examination and venipuncture. The Profile of Mood States (POMS) provided measures of overall psychological distress as well as specific mood states. Pyridoxine deficiency status (a categorical measure of deficient vs. adequate status) was determined with a bioassay of erythrocyte aspartate aminotransferase activity.Results: Pyridoxine deficiency was a significant predictor of increased overall psychological distress in this model, controlling for life stressors, social support, coping style, and HIV-1 serostatus. In post hoc analyses of specific mood state effects, pyridoxine deficiency status was significantly associated with increases in depressed, fatigued, and confused mood levels, but not with those of anxiety, anger, or vigor.Discussion: These findings suggest that adequate pyridoxine status may be necessary to avert psychological distress in the setting of bereavement. Inasmuch as pyridoxine is a cofactor for 5-hydroxytryptophan decarboxylase--an enzyme in the biosynthesis pathway of serotonin--serotonin level in the brain is implicated as the mediating factor. [ABSTRACT FROM AUTHOR]