Aging and neuro-AIDS conditions and the changing spectrum of HIV-1-associated morbidity and mortality.

Older individuals (>50 years of age) now comprise over 11% of patients with AIDS in the United States. This percentage is expected to continue to grow, due both to the improved longevity of patients prescribed highly active antiretroviral therapy (HAART) and to new infections among older individuals. This review focuses on the neuropsychiatric and neurological conditions that are most likely to be affected by advancing age-HIV-1-associated cognitive-motor disorder, peripheral neuropathy, progressive multifocal leukoencephalopathy, primary CNS lymphoma, and risk for cerebrovascular accident. Age associations with incidence of these disorders and with treatment foci are specified. Implications for future changes in management are discussed.

A bereavement support group intervention affects plasma burden of human immunodeficiency virus type 1. Report of a randomized controlled trial.

OBJECTIVES: This study investigates the potential impact of a bereavement support group on plasma viral load. METHODS: A randomly selected subsample of human immunodeficiency virus type 1 (HIV-1)-positive homosexual men participating in a controlled clinical trial of a bereavement support group intervention was studied. The intervention consisted of one 90-minute group session per week for 10 weeks. The plasma HIV-1 RNA copy number was measured at baseline and after intervention (10 weeks) by the Roche AMPLICOR assay. RESULTS: There was a significant effect of the intervention on the change on the plasma HIV-1 RNA copy number (limited control model, beta = -0.49, p = 0.02; extended control model, beta = -0.37, p = 0.01), independent of antiretroviral therapies; prophylactic therapies against potentially lethal HIV-1 associated conditions; CD4 cell count; viral load; and Centers for Disease Control and Prevention clinical disease stage at baseline. CONCLUSIONS: Bereavement support group interventions may prove to be not only a primary therapy for psychologic distress after bereavement but also an adjunctive therapy for sustained control of plasma viral load in conjunction with highly active antiretroviral therapy in this population.

Exercise treatment for major depression: maintenance of therapeutic benefit at 10 months.

OBJECTIVE: The purpose of this study was to assess the status of 156 adult volunteers with major depressive disorder (MDD) 6 months after completion of a study in which they were randomly assigned to a 4-month course of aerobic exercise, sertraline therapy, or a combination of exercise and sertraline. METHODS: The presence and severity of depression were assessed by clinical interview using the Diagnostic Interview Schedule and the Hamilton Rating Scale for Depression (HRSD) and by self-report using the Beck Depression Inventory. Assessments were performed at baseline, after 4 months of treatment, and 6 months after treatment was concluded (ie, after 10 months). RESULTS: After 4 months patients in all three groups exhibited significant improvement; the proportion of remitted participants (ie, those who no longer met diagnostic criteria for MDD and had an HRSD score <8) was comparable across the three treatment conditions. After 10 months, however, remitted subjects in the exercise group had significantly lower relapse rates (p = .01) than subjects in the medication group. Exercising on one's own during the follow-up period was associated with a reduced probability of depression diagnosis at the end of that period (odds ratio = 0.49, p = .0009). CONCLUSIONS: Among individuals with MDD, exercise therapy is feasible and is associated with significant therapeutic benefit, especially if exercise is continued over time.

Cobalamin level is related to self-reported and clinically rated mood and to syndromal depression in bereaved HIV-1(+) and HIV-1(-) homosexual men.

OBJECTIVE: An examination of the relationship of plasma cobalamin (vitamin B(12)) level to overall psychological distress, specific mood states, and major depressive disorder was conducted in 159 bereaved men (90 HIV-1(+) and 69 HIV-1(-)). METHODS: The relationship of a continuous measure of cobalamin level to psychological distress was examined, while controlling for HIV-1 serostatus, life stressors, social support, and coping styles. RESULTS: Of this sample, 23.9% were either overtly or marginally cobalamin deficient; however, the deficiency rate was not significantly different by HIV-1 serostatus. Cobalamin level was inversely related to self-reported overall distress level and specifically to depression, anxiety, and confusion subscale scores, as well as to clinically rated depressed and anxious mood. Lower plasma cobalamin levels also were associated with the presence of symptoms consistent with major depressive disorder. CONCLUSION: These findings suggest that cobalamin level may be physiologically related to depressed and anxious mood level, as well as to syndromal depression.

HIV-1-Associated Cognitive-Motor Disorders: A Research-Based Approach to Diagnosis and Treatment.

The diagnosis of human immunodeficiency virus type 1 (HIV-1)-associated cognitive-motor disorder--either minor cognitive-motor disorder (MCMD) or HIV-1-associated dementia (HAD)--is fraught with potential pitfalls for the clinician. Before making such a diagnosis, clinicians should exclude other etiologies by using neuroimaging, lumbar puncture, and serum chemistries to screen for opportunistic and non-opportunistic infections of the brain and meninges. Clinicians should also consider psychoneurotoxicity (caused from the use of psychoactive substances and prescribed medications) and psychopathology, such as mood, anxiety, and other disorders. In addition, a thorough medical history and physical examination, including a complete neurologic and neuropsychiatric mental status examination, are necessary for an accurate diagnosis. There is also a need for standardized neuropsychological and functional status tests, since the diagnostic criteria for these disorders are partly based on these criteria. Treatment targets should include subclinical cognitive-motor impairment and neuroprotection, as well as MCMD and HAD. Currently, zidovudine remains the best proven treatment for these disorders, but other nucleoside reverse transcriptase inhibitors, as well as nonnucleoside reverse transcriptase inhibitors and protease inhibitors, show promise, and selected agents from these classes are being tested in clinical trials. Other areas that should be investigated are the modulation of inflammatory mediators (such as tumor necrosis factor alpha), neurotransmitter manipulation (especially of dopamine), and nutritional interventions.

Theory-Driven Interventions in Psychoneuroimmunology and HIV-1 Infection.

Psychoneuroimmunology (PNI) is a rapidly evolving multidisciplinary field founded on the premise that psychosocial factors, the central nervous system, and the immune system are intimately linked. Following publication of scientific evidence supporting this link, a number of animal and human studies have been published, both inside and outside the area of human immunodeficiency virus (HIV) infection and acquired immunodeficiency syndrome. These studies support the existence of bidirectional feedback mechanisms operating between the brain and the immune system. To date, however, there is no all-encompassing model that predicts individual differences in the relationship among psychosocial factors, immunologic measures, and clinical disease progression in HIV type 1 (HIV-1) infection. This variability in human response has been explained by a number of cofactors (host as well as environmental) that appear to accelerate the course of the disease. Since psychosocial factors are highly amenable to behavioral interventions, several models for intervention research have been proposed to evaluate whether such interventions can enhance immune functioning, thereby curtailing disease progression. Examination of these interventions in the context of PNI and HIV-1 infection, however, is rather limited. Therefore, researchers and clinicians must not only consider conceptualizations and paradigms in this area of research, but also focus on empirically testable, theory-driven models that allow for the unique characteristics of individual patients.

HIV-1 Infection, Neuroendocrine Abnormalities, and Clinical Outcomes.

Different lines of evidence suggest that human immunodeficiency virus type 1 (HIV-1) infection is complicated by a variety of adverse effects on neuroendocrine systems. Soon after the discovery of HIV-1, reports began to appear suggesting that a number of neurotransmitter and neuroendocrine activities were negatively impacted by this infection. In 1987 it was observed that fine-needle aspiration of the lung in patients with acquired immunodeficiency syndrome resulted in syncopal reactions. Subsequently, an abnormality in the autonomic nervous system was reported in these patients. However, investigations in this area have remained limited due to the assumption that HIV-1-mediated activation of various endocrine systems was related to the major life stressor of living with a fatal disease. Evidence accumulated over the years has indicated, instead, that there are various other mechanisms in addition to life stressors that also play an important role in negatively impacting the neuroendocrine systems in this infection. This article examines various developments that have taken place in this area in order to provide avenues for future research.

Nutritional Contributions to the CNS Pathophysiology of HIV-1 Infection and Implications for Treatment.

Nutritional deficiencies are commonplace in patients with human immunodeficiency virus type 1 (HIV-1) infection, and recent research has indicated that nutritional factors may play an important role in the pathogenesis of HIV-1 disease. Although nutritional deficiencies are unlikely to be the primary causative factor in disease progression, they may contribute to cognitive dysfunction, neurologic abnormalities, mood disturbance, and immune dysregulation associated with HIV-1 infection. Furthermore, deficiencies of specific micronutrients have been associated with increased risk of HIV-1-associated mortality. This article will briefly summarize the role of macronutrient deficiency, the interactions of specific micronutrient deficiencies with neuropsychiatric functioning, and the role of these factors in HIV-1 disease progression. Since recent research has shown that normalization of many nutritional deficits and supplementation beyond normal levels are associated with improvements in neuropsychiatric functioning, potential treatment implications will also be discussed.

Current issues in the diagnosis and management of malingering.

Malingering is a diagnosis that is frequently avoided by physicians. When there is a claim of symptoms or diseases that either are exaggerated or do not exist, the diagnosis of malingering should be entertained. Malingering is associated with a conscious intent to deceive in order to obtain a known gain. Psychoanalytical, criteria-based (DSM-IV) and 'adaptational' models have been advanced to explain malingering. The differential diagnosis of malingering includes factitious disorder, the somatoform disorders, the dissociative disorders, and specific medical conditions without somatoform disorder. Upon consideration of the differential diagnosis, confirmation of the suspicion of malingering is still required in order to make the diagnosis. Confirmation can be achieved by observation or by inferential methods. Observation can be employed with controlled environment observation or with covert, 'real-world' surveillance; inference may involve primary and/or secondary source information. It may be concluded that a greater attempt should be made to identify this diagnosis, as the cost of malingering to society is considerable.

A randomized controlled clinical trial of a bereavement support group intervention in human immunodeficiency virus type 1-seropositive and -seronegative homosexual men.

BACKGROUND: Bereavement is a severe and frequent stressor among those infected with human immunodeficiency virus type 1 (HIV-1) and those affected by the acquired immunodeficiency syndrome epidemic. This study examined the impact of a research-derived, semistructured, bereavement support group among HIV-1-seropositive and HIV-1-seronegative homosexual men having lost a close friend or intimate partner to the acquired immunodeficiency syndrome within the prior 6 months. METHODS: A total of 166 subjects (97 HIV-1 seropositive; 69 HIV- 1 seronegative) were randomly assigned to groups of homogeneous HIV-1 serostatus or to their respective control group. Subjects were assessed at entry and at 10 weeks with psychosocial questionnaires, a semistructured interview for psychopathology, a medical history and physical examination, urine collection, and phlebotomy. RESULTS: For a composite score of psychological distress and grief as well as the distress component, scores were significantly lower after the intervention by analyses against baseline scores, with and without control variables for other factors affecting distress level. A significant reduction in grief level was found only in the analysis that included control variables. Control subjects showed no significant decrements in overall distress, although a significant decrement in grief level was observed. CONCLUSION: A brief group intervention can significantly reduce overall distress and accelerate grief reduction in a sample of bereaved subjects unselected for psychopathology or at high risk for subsequent maladjustment.

Plasma pyridoxine deficiency is related to increased psychological distress in recently bereaved homosexual men.

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.

A bereavement support group intervention is longitudinally associated with salutary effects on the CD4 cell count and number of physician visits.

A randomized, controlled, clinical trial was conducted to examine the impact of a semistructured, 10-week, once weekly, 90-min/session bereavement support group intervention on immunological, neuroendocrine, and clinical health status in human immunodeficiency virus type 1-seropositive (HIV-1+) and HIV-1-seronegative (HIV-1-) homosexual men, compared to a standard of care control condition. A total of 119 homosexual men (74 HIV-1+ and 45 HIV-1-) were assessed at baseline, 10 weeks, and 6 months follow-up. At the 6-month follow-up assessment, the intervention groups exhibited significant beneficial effects compared to controls on changes in CD4 cell, total T-lymphocyte, and total lymphocyte counts, when baseline levels, antiretroviral medication use, CDC stage of disease, and other potentially confounding factors were accounted for. There was no statistically significant effect on the CD4/CD8 ratio or on the CD8 cell count. The effect on CD4 cell count was associated with group attendance and with changes in plasma cortisol level. Plasma cortisol levels decreased significantly among intervention subjects, compared to controls. A significantly reduced number of health care visits over the 6-month follow-up period among the intervention subjects supported the clinical relevance of the immunological changes observed for both HIV-1+ and HIV-1- individuals. These results indicate that behavioral interventions may have salutary immunological and clinical health effects following bereavement among HIV-1-infected individuals. The effect in HIV-1- individuals suggests that this bereavement support group intervention might have similar salutary effects in the general population. Potential effects of such interventions on clinical HIV disease progression are of interest and should be studied.

Psychological distress in HIV-1 disease in relationship to hypocholesterolemia.

OBJECTIVE: Altered levels of serum cholesterol, which are prevalent in early HIV-1 infection, have been associated with disturbances in mood state and behavior. The objective of this study was to evaluate the relationship of serum cholesterol status and psychological distress in HIV-1 seropositive and seronegative men. METHOD: The association between serum cholesterol level and psychological distress, measured with the Profile of Mood States (POMS), was examined in 169 individuals (117 HIV-1 seropositive and 52 seronegative homosexual men), controlling for negative life events, social support, coping style, and HIV-1 serostatus. RESULTS: Individuals with hypocholesterolemia (serum cholesterol levels < 150 mg/dL), exhibited significantly higher levels of distress, relative to individuals with values of cholesterol > 150 mg/dL (p = 0.01). HIV-1 seropositive men had significantly lower cholesterol levels (p = 0.0001) and higher levels of distress than the seronegative men (p = 0.03). A significant interaction between negative life events and cholesterol status was demonstrated as well (p = 0.04). CONCLUSIONS: Hypocholesterolemia appears to be associated with increased psychological distress. Whereas the causal direction of the cholesterol-distress association cannot be specified, our results suggest that HIV-1 infected men with low cholesterol levels may benefit from being monitored for changes in distress level, so that appropriate psychosocial intervention can be instituted, as necessary.