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.

Integrating mental health services into primary care for HIV-infected pregnant and non-pregnant women: Whole Life--a theoretically derived model for clinical care and outcomes assessment.

Poor women of color who are disproportionately both infected and affected by HIV/AIDS also face multiple lifestyle and psychosocial burdens that complicate effective delivery of health care, thereby contributing to their poorer prognosis. Addressing these factors within the context of HIV/AIDS primary care for women is the aim of Whole Life, a program to integrate mental health services into primary care for HIV-infected pregnant and non-pregnant women. Whole Life utilizes a theoretically derived clinical services model that provides data for both clinical care and patient outcomes research within the constraints of a clinical setting. During a woman's first two clinic visits, data are gathered in structured interviews with standardized instruments-adapted for relevance to the population-that meet clinical and service needs, as well as measure components of the Whole Life model. Interviews are conducted by existing front-line staff who have been trained in using these instruments to gather information typically recorded in clinical notes. The implementation of Whole Life to date clearly demonstrates the feasibility of mental health-primary care services integration in a publicly funded HIV primary care clinic serving poor women of color.

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.

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.

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.

Mild cognitive impairment and risk of mortality in HIV-1 infection.

HIV-1-associated cognitive impairment has only been preliminarily investigated for associations with mortality. The authors examined 119 HIV-1-positive homosexual men (asymptomatic: n = 96; early symptomatic: n = 23). At follow-up (to 3.5 years), there were 105 survivors and 14 nonsurvivors. Those at the 25th percentile in response speeds and in long-term memory retrieval accuracy were at 6.4 (P < 0.02) and 3.5 (P < 0.05) times increased mortality risk, respectively, of those at the 75th percentile--independent of baseline CDC clinical stage, CD4 cell count, hemoglobin level, antiretroviral and prophylactic medication use, and sociodemographics. Cognitive impairment should be identified early--for maximization of both functional status and survival time.

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.

Personality traits and long-term health status. The influence of neuroticism and conscientiousness on renal deterioration in type-1 diabetes.

Stringent long-term control of blood glucose concentration in patients with insulin-dependent diabetes mellitus (IDDM) can decrease albuminuria, presumably forestalling development of renal insufficiency. Personality characteristics may influence a diabetic patient's ability and willingness to follow a prescribed regimen to achieve glycemic control. This study investigated the relationship of 2 personality factors to renal deterioration time (from initiation of insulin therapy to renal failure) in 85 patients with IDDM and end-stage renal disease. Persons moderate in the personality trait of neuroticism and high in conscientiousness had renal deterioration times that were 12 years longer than persons with either high or low neuroticism and low conscientiousness, presumably because of better self-care. The implications of this study's findings are discussed.

Bereavement is associated with time-dependent decrements in cellular immune function in asymptomatic human immunodeficiency virus type 1-seropositive homosexual men.

Seventy-nine human immunodeficiency virus type 1 (HIV-1)-seropositive homosexual men participating in a longitudinal study of HIV-1 infection were assessed twice, 6 months apart, to investigate associations between bereavement and cellular immune function. Subjects were assessed by using a theory-driven model comprising life stressors, social support and coping style, and control variables. Natural killer cell cytotoxicity was decreased among the bereaved at both times. Lymphocyte proliferative response to phytohemagglutinin was decreased among the bereaved at the second time point but not at the first. These functional immune decrements are associated with increased neuroendocrine responses of the sympathetic adrenomeduallary system as well as the limbic-hypothalamic-pituitary-adrenal axis. Implications for differential neuroendocrine responses over time are discussed. Active coping style was independently and positively related to both immune measures. The results imply that a bereavement support group intervention merits investigation for an effect on immunological measures and clinical progression of HIV-1 infection as well as grief resolution.

Pathogenesis of cognitive complaints in patients on hemodialysis.

Memory-concentration complaints are a common symptom among end-stage renal disease patients receiving hemodialysis. However, assuming an organic basis for these complaints might lead to unnecessary and expensive testing. To further explore the etiology of cognitive complaints, this study examined the contribution of demographic, neuropsychological, medical, affective, and personality variables to memory-concentration complaints in 426 hemodialysis patients. Following stepwise multiple regression to identify the best predictor variables within each domain, hierarchical multiple-regression analysis determined the significant predictors of memory-concentration complaints. Education, digit symbol score, and hemoglobin jointly accounted for approximately 7% of the variance. Cognitive (psychological) symptoms of depression explained an additional 9% of variance. Somatic symptoms of depression did not significantly contribute, whereas state anxiety did. Finally, personality variables collectively accounted for another 9% of variance. Overall, the model accounted for 28% of explained variance in memory-concentration complaints. These findings demonstrate that affect and personality factors are more predictive of memory-concentration complaints in hemodialysis patients than are neuropsychological or medical factors. The clinical implication is that the initial response to memory-concentration complaints in these patients should be evaluations of psychological condition.

Impact of vitamin B6 status on psychological distress in a longitudinal study of HIV-1 infection.

OBJECTIVE: Inadequate vitamin B6 status has been associated with altered neuropsychiatric function, possibly through its effect on the metabolism of neurotransmitters, including serotonin (5-HT). The present eighteen month longitudinal study evaluated the relationship between vitamin B6 status and psychological distress in HIV-1 infected individuals, controlling for the influence of negative life events, social support and coping style. METHOD: Biochemical measurements of nutritional status, and dietary intake evaluations were obtained in HIV-1 seropositive homosexual men, (at baseline: CDC Stages II and III, n = 70; Stage IVA, IVC2 n = 18) at six month intervals. Alterations in nutrient status (e.g., vitamin B6 adequate to inadequate; inadequate to adequate), were compared with changes in psychological distress, measured by the Profile of Mood States, using a multiple regression analysis. RESULTS: A significant decline in psychological distress was demonstrated with normalization of vitamin B6 status from inadequate to adequate status (p < 0.02). A decrease in psychological distress was also observed with increased tryptophan intake in subjects who were vitamin B6 adequate (p < 0.02). CONCLUSIONS: Significant effects for the nutritional variables remained even when negative life event stressors, social support, and coping style were controlled, suggesting that vitamin B6 status may be an important co-factor in determining level of psychological distress over time in HIV-1 infected individuals.

Active coping style is associated with natural killer cell cytotoxicity in asymptomatic HIV-1 seropositive homosexual men.

The aim of this study was to examine the hypothesis that a psychosocial model was associated with natural killer cell cytotoxicity (NKCC) in HIV-1 infection. A sample of 62 HIV-1 seropositive homosexual men at CDC stages II and III were given a psychosocial battery assessing life stressors, social support, and coping style. A regression model quantifying these variables along with control variables for alcohol use, substance use and nutritional status was estimated. Active coping style was directly and positively associated with NKCC, and trends toward a negative relationship of life stressors and a buffering effect of social support on lives stressors were also observed. The results suggest that (1) control variables should be included with psychosocial models and that (2) psychosocial factors, especially active coping, may have a deterrent effect on loss of NK cell function. Active coping style may merit a specific focus in future research of life stressors and the immune system.

Cognition and immune function in HIV-1 infection.

OBJECTIVES: To determine (1) whether there were differences in cognition between HIV-1-seropositive and HIV-1-seronegative homosexual men and (2), if so, whether these differences could be explained by the degree of immunosuppression [i.e., CD4 cell count and immunoglobulin A (IgA) levels]. DESIGN: A cross-sectional design was used to compare 66 HIV-1-seropositives (Centers for Disease Control stages II and III, n = 56; stages IVA and IVC-2, n = 10) and 37 HIV-1-seronegatives. The HIV-1-seropositives were classified into three immune groups based on their CD4 cell count (x 10(6)/l) and serum IgA level (mg/dl): (1) moderate [(n = 35) CD4 greater than 400, IgA less than 300]; (2) mixed [(n = 22) either CD4 greater than 400 and IgA greater than 300 or CD4 less than 400 and IgA less than 300] and (3) poor [(n = 9) CD4 less than 400, IgA greater than 300]. HIV-1-seronegatives formed the 'good' immune group (CD4 greater than 400 and IgA less than 300). METHODS: The four groups were compared on tests of verbal and visual memory, information-processing speeds, visuospatial skills, language processes, attention, psychomotor reaction time, and mental status. Factors other than HIV-1 sero-status that can influence cognitive performance were tested as covariates. RESULTS: HIV-1-seropositives had slower information-processing speeds and decreased verbal and visual memory, compared with HIV-1-seronegatives. These differences in cognition were not due to differential immunosuppression or to clinical status among the HIV-1-seropositives. CONCLUSIONS: Cognitive alterations occur in HIV-1-infected individuals before AIDS and appear to be independent of clinical status and degree of immunosuppression as measured by CD4 cell count and IgA levels.

Plasma vitamin B12 level as a potential cofactor in studies of human immunodeficiency virus type 1-related cognitive changes.

Studies of cognitive function in subjects with human immunodeficiency virus type 1 (HIV-1) infection who remain relatively asymptomatic (ie, Centers for Disease Control stages II and III) have provided widely variable estimates of cognitive impairment. In view of the finding that approximately 25% of asymptomatic HIV-1-infected subjects demonstrate either marginal or overt vitamin B12 deficiency, we have investigated plasma vitamin B12 status as a potential cofactor in studies of HIV-1-related cognitive impairment. When cognition was assessed in asymptomatic (Centers for Disease Control stages II and III) HIV-1-infected participants taking into consideration vitamin B12 status, those subjects with low plasma vitamin B12 levels (less than 180 pmol/L) performed more poorly than did those with normal (greater than or equal to 180 pmol/L) vitamin B12 status on specific measures of information processing speed and visuospatial problem-solving skills. These findings suggest that concurrent vitamin B12 deficiency may be a cofactor in subtle cognitive changes observed in the asymptomatic stages of HIV-1 infection. These differences in prevalence of low plasma vitamin B12 levels may help to explain differences among studies in the proportion of HIV-1-infected subjects showing cognitive impairment.

Immune function and anti-HTLV-I/II status in anti-HIV-1-negative intravenous drug users receiving methadone.

PURPOSE: The study objective was to evaluate the effects of long-term methadone use and human T-cell leukemia virus (HTLV) types I and II seropositivity on the distribution of lymphocyte subsets and on lymphocyte function as measured in vitro in intravenous drug users seronegative for human immunodeficiency virus type 1 (HIV-1). PATIENTS AND METHODS: Anti-HIV-1-negative intravenous drug users receiving methadone maintenance therapy (n = 24) were studied in a Veterans Administration drug abuse treatment center. These subjects were compared to 38 age- and sex-matched control subjects who did not abuse drugs. HIV-1 and HTLV serostatus was determined by repetitive enzyme-linked immunosorbent assay and confirmed by immunoblot. Lymphocyte subsets were determined by two-color flow cytometry. Lymphocyte function was measured by proliferative response to plant mitogens and by natural killer (NK) cell-mediated cytotoxicity to a tumor cell target. RESULTS: Significant differences were seen in lymphocyte phenotype in the methadone-treated group, with elevations in the T-cell helper subset CD4+CD26+; in CD8 and CD8+I2+ cells, suppressor/cytotoxic T lymphocytes, and activated suppressor/cytotoxic T cells; and in CD2+CD26+ cells and activated total T lymphocytes. Lymphocyte function was suppressed in the methadone group, with poor responses to pokeweed mitogen and phytohemagglutinin in culture. Moreover, NK-cell cytotoxicity was significantly reduced in the methadone group. None of these immunologic differences were attributable to HTLV serostatus. CONCLUSION: The immune abnormalities seen suggest that a clinically significant degree of immune impairment exists in methadone-treated intravenous drug users. However, these abnormalities could not be explained by the presence of other retroviruses in this HIV-1-negative study group, as there was no significant difference in immune function when HTLV-seropositive patients were compared to HTLV-seronegative subjects treated with methadone.

A stress-moderator model of distress in early HIV-1 infection: concurrent analysis of life events, hardiness and social support.

A stress moderator framework was employed to investigate the relationship of negative life events, hardiness and social support to psychological distress among 67 asymptomatic HIV-1 seropositive gay males. Both main effects and stress moderator (interaction) models were evaluated. Main effects were found for negative life events and social support but not hardiness (either as commitment or overall hardiness); no moderator effects emerged. Results were the same whether events were quantified as negative impact or as number of events, and were in the predicted direction--life events associated with greater distress, social support with less distress. The present study replicates for early HIV-1 infection findings obtained in non-HIV-infected samples about the influence on psychological distress of negative life events and social support. Methodological limitations, possible explanations for the absence of stress moderator effects, and clinical implications of the findings are discussed.