HIV/AIDS-related stigma, immediate families, and proactive coping processes among a clinical sample of people living with HIV/AIDS in Philadelphia, Pennsylvania.

People living with HIV/AIDS (PLWHA) engage in proactive coping behaviors to minimize the risk of interpersonal stigma. This study explores proactive coping processes in navigating HIV/AIDS-related stigma within immediate families. Data for this study come from 19 one-on-one, qualitative interviews with a diverse, clinical sample of PLWHA in Philadelphia, PA. Thematic analysis indicated that participants continue to experience enacted, anticipated, and internalized forms of HIV/AIDS-related stigma. Participants discussed status concealment and selective disclosure as proactive coping resulting from anticipated stigma and physical distancing as proactive coping motivated by internalized HIV/AIDS-related stigma. Study findings demonstrate how living with a stigmatized condition can affect PLWHA social interactions with close networks like immediate families, specifically in eliciting stigma-avoidant behaviors. Anti-stigma efforts that educate immediate families to overcome stigmatizing attitudes and provide HIV-positive family members with high-quality social support should be coupled with efforts that target health-promotive self-management strategies for PLWHA.

The Selective Serotonin Reuptake Inhibitor Citalopram Decreases Human Immunodeficiency Virus Receptor and Coreceptor Expression in Immune Cells.

BACKGROUND: This study investigated whether the selective serotonin reuptake inhibitor (SSRI) citalopram downregulates the expression of the human immunodeficiency virus (HIV) receptor cluster of differentiation 4 (CD4) and coreceptors chemokine receptor type 5 and chemokine-related receptor type 4 (CCR5 and CXCR4) on peripheral blood mononuclear cells (PBMCs) and macrophages ex vivo as a potential mechanism of reducing susceptibility to HIV infection. METHODS: The sample included 150 participants 18-58 years old (59% women, 65% African American, 61% with depression). Monocyte-depleted PBMCs were treated with phytohemagglutinin for 72 hours and then cultured in the presence of interleukin-2 with vehicle control or the SSRI (10(-6) mol/L) for 2 hours. To generate monocyte-derived macrophages, monocytes were cultured for 7 days, after which either vehicle control or SSRI (10(-6) mol/L) was added for 2 hours. RNA was collected from both cell types, and messenger RNA expression of CD4, CCR5, and CXCR4 was measured by real-time polymerase chain reaction. RESULTS: In PBMCs, SSRI treatment decreased expression of CD4 (p = .009), CCR5 (p = .008), and CXCR4 (p < .0001). In monocyte-derived macrophages, SSRI treatment decreased expression of CD4 (p < .0001) and CXCR4 (p = .0003), but not CCR5 (p = .71). The suppressive effects of the SSRI on receptor expression did not differ as a function of depression diagnosis or depressive symptom severity. CONCLUSIONS: Treatment with the SSRI at a physiologic dose decreased CD4, CCR5, and CXCR4 expression on PBMCs and macrophages ex vivo. These findings suggest that SSRI treatment, independent of depression status, downregulates HIV receptor and coreceptor expression and may reduce susceptibility of immune cells to HIV infection and decrease inflammation. If clinical trials confirm the present findings, ultimately there may be a role for using SSRI treatment adjunctively in HIV and acquired immunodeficiency syndrome.

A Brief Examination of Integrated Care in Undergraduate Medical Education.

OBJECTIVE: This study examines how behavioral and physical health are currently integrated in undergraduate medical education, both in the classroom and during clinical rotations. METHODS: Members of the Association of Directors of Medical Student Education in Psychiatry (n = 215) were invited to complete a short survey on the integration of physical and behavioral health at their institution. RESULTS: In addition to undergraduate medical courses traditionally taught by psychiatrists, behavioral science topics are often addressed in neurology, reproduction, and doctoring courses. During clinical rotations, behavioral health topics are most likely taught during the family medicine clerkship and, conversely, least likely during the surgery clerkship; furthermore, behavioral health topics are much less likely to be taught by psychiatrists during clinical rotations. CONCLUSIONS: Integration of behavioral and physical health in medical education is beginning to occur in a meaningful context.

Health Outcomes of HIV-Infected People with Mental Illness.

Improving outcomes for people with HIV and mental illness will be critical to meeting the goals of the US National HIV/AIDS Strategy. In a retrospective analysis of the 2008-2010 cycles of the locally representative Philadelphia Medical Monitoring Project, we compared the proportions of HIV-infected adults with and without mental illness: (1) retained in care (≥2 primary HIV visits separated by ≥90 days in a 12-month period); (2) prescribed antiretroviral therapy (ART) at any point in a 12-month period; and (3) virally suppressed (HIV-1 RNA ≤200 copies/mL at the last measure in the 12-month period). Multivariable regression assessed associations between mental illness and the outcomes, adjusting for age, gender, race/ethnicity, insurance, alcohol abuse, injection drug use, CD4 count, and calendar year. Of 730 HIV-infected persons, representative of 9409 persons in care for HIV in Philadelphia, 49.0 % had mental illness. In adjusted analyses, there were no significant differences in retention (91.3 vs. 90.3 %; AOR 1.30, 95 % CI 0.63-2.56) and prescription of ART (83.2 vs. 88.7 %; AOR 0.79, 95 % CI 0.49-1.25) between those with and without mental illness. However, mentally ill patients were less likely to achieve viral suppression than those without mental illness (65.9 vs. 74.4 %; AOR 0.64, 95 % CI 0.46-0.90). These findings argue for the need to optimize ART adherence in this population.

Attitude and perceptions of the other underrepresented minority in surgery.

OBJECTIVE: To perform a national climate survey of general surgery residents regarding attitudes and perceptions of the influence of sexual orientation on the training experience. METHODS: A cross-sectional voluntary online survey was distributed to all Accreditation Council for Graduate Medical Education-accredited general surgery programs. Residents self-identified as heterosexual, lesbian, gay, or bisexual. Descriptive statistics were performed. For the purposes of further analysis, respondents were classified as heterosexual or LGBT. Demographic characteristics and survey responses were examined by sexual orientation using the Fisher exact test. RESULTS: Of 388 resident respondents, 10 identified as lesbian (2.6%), 24 as gay (6.3%), and 9 as bisexual (2.4%). More than 30% of LGBT residents did not reveal their sexual orientation when applying for general surgery residency owing to fear of not being accepted. No statistical differences were found between LGBT and heterosexual residents regarding future career plans, happiness at work, good program fit, and rapport with fellow residents. Although no differences were found in relationship status between LGBT and heterosexual residents, more LGBT residents reported feeling uncomfortable openly discussing their spouse/partner with fellow residents (36% vs 3.0%, p < 0.001) and with surgical attending physicians (59% vs 9.3 %, p < 0.001) when compared with heterosexual peers. Additionally, LGBT residents felt more uncomfortable bringing their spouse/partner to formal surgery department events (42% vs 2.7%, p < 0.001). Among all respondents, 54% (n = 206) witnessed homophobic remarks by nurses and residents and 30% (n = 114) by surgical attending physicians. Of LGBT residents, 57% reported actively concealing their sexual orientation from fellow residents owing to fear of rejection and 52% from surgical attending physicians owing to fear of poor evaluations. LGBT residents reported experiencing targeted homophobic remarks by fellow residents (21%) and by surgical attending physicians (12%). None of the surgical residents who experienced directed homophobic remarks reported the event to their supervisors for reasons including fear of reprisal (13%-17%), not wanting to create more "trouble" (25%-50%), and a belief that nothing would be done about the event (17%-25%). CONCLUSION: Now, more than ever, issues related to sexual orientation have been at the forefront of political and public attention. No data exist that explore how these issues affect the training experience of general surgery residents. Our study showed that although there was no difference overall in reported work happiness or program fit, LGBT residents reported a greater need to conceal their personal lives from their surgery program peers and attending physicians. Whether these differences affect patient care, team work, career satisfaction, and personal cost of surgical training warrants further study.

The glucocorticoid antagonist RU-486 suppresses HIV infectivity and replication.

The effects of RU-486, a glucocorticoid antagonist, on HIV infection and replication in depressed and nondepressed women were studied using ex vivo models of HIV infection. RU-486 treatment of cells decreased HIV reverse transcriptase activity of monocyte-derived macrophages in a model of acute infectivity. RU-486 also decreased HIV viral replication in the chronically-infected T-cell line ACH-2, but not in the promonocyte cell line U1. No differences were associated with depression status. Thus, glucocorticoid antagonism may suppress HIV infectivity and replication ex vivo. Studies to determine the role of glucocorticoid antagonists in the host defense against HIV should be performed.

Selective serotonin reuptake inhibitor suppression of HIV infectivity and replication.

OBJECTIVE: To test the hypothesis that the selective serotonin reuptake inhibitor (SSRI) citalopram would down-regulate human immunodeficiency virus (HIV) infectivity and that the greatest effects would be seen in people with depression. Depression is a risk factor for morbidity and mortality in HIV/acquired immune deficiency syndrome. Serotonin (5-HT) neurotransmission has been implicated in the pathobiology of depression, and pharmacologic therapies for depression target this system. The 5-HT transporter and 5-HT receptors are widely distributed throughout the central nervous and immune systems. Depression has been associated with suppression of natural killer cells and CD8(+) lymphocytes, key regulators of HIV infection. METHODS: Ex vivo models for acute and chronic HIV infection were used to study the effects of citalopram on HIV viral infection and replication in 48 depressed and nondepressed women. For both the acute and chronic infection models, HIV reverse transcriptase activity was measured in the citalopram treatment condition and the control condition. RESULTS: The SSRI significantly down-regulated the reverse transcriptase response in both the acute and chronic infection models. Specifically, citalopram significantly decreased the acute HIV infectivity of macrophages. Citalopram also significantly decreased HIV viral replication in the latently infected T-cell line and in the latently infected macrophage cell line. There was no difference in down-regulation by depression status. CONCLUSIONS: These studies suggest that an SSRI enhances natural killer/CD8 noncytolytic HIV suppression in HIV/acquired immune deficiency syndrome and decreases HIV viral infectivity of macrophages, ex vivo, suggesting the need for in vivo studies to determine a potential role for agents targeting serotonin in the host defense against HIV.

Selective serotonin reuptake inhibitor and substance P antagonist enhancement of natural killer cell innate immunity in human immunodeficiency virus/acquired immunodeficiency syndrome.

BACKGROUND: Natural killer (NK) cells play an important role in innate immunity and are involved in the host defense against human immunodeficiency virus (HIV) infection. This study examines the potential role of three underlying regulatory systems that have been under investigation in central nervous system research as well as immune and viral research: serotonin, neurokinin, and glucocorticoid systems. METHODS: Fifty-one HIV-seropositive subjects were recruited to achieve a representative sample of depressed and nondepressed women. The effects of a selective serotonin reuptake inhibitor (SSRI), a substance P (SP) antagonist, and a glucocorticoid antagonist on NK cell function were assessed in a series of ex vivo experiments of peripheral blood mononuclear cells from each HIV-seropositive subject. RESULTS: Natural killer cell cytolytic activity was significantly increased by the SSRI citalopram and by the substance P antagonist CP-96345 relative to control conditions; the glucocorticoid antagonist, RU486, showed no effect on NK cytotoxicity. Our results suggest that the effects of the three agents did not differ as a function of depression. CONCLUSIONS: Our findings provide evidence that NK cell function in HIV infection may be enhanced by serotonin reuptake inhibition and by substance P antagonism. It remains to be determined if HIV-related impairment in not only NK cytolytic activity but also NK noncytolytic activity can be improved by an SSRI or an SP antagonist. Clinical studies are warranted to address these questions and the potential roles of serotonergic agents and SP antagonists in improving NK cell immunity, delaying HIV disease progression, and extending survival with HIV infection.

Association of resolution of major depression with increased natural killer cell activity among HIV-seropositive women.

OBJECTIVE: Depression is a potential risk factor for morbidity and mortality among patients with numerous medical conditions, including HIV disease, and it is also associated with decrements in immune function, such as natural killer (NK) cell activity. This study examined whether improvements in the diagnostic status of major depression are related to increases in NK cell activity among HIV-seropositive women. METHOD: HIV-seropositive women were recruited as part of a longitudinal cohort study and underwent comprehensive medical and psychiatric evaluations during a 2-year period. Fifty-seven women had complete NK cell activity and depression data measured at two time points and were examined for associations between changes in depression status and alterations in NK cell activity over time. RESULTS: Among the 57 HIV-seropositive women, improvements in the diagnostic status of depression and decreases in scores on the 17-item Hamilton Depression Rating Scale were significantly associated with increases in NK cell activity over time, as measured in lytic units. Eleven women (19.3%) had a major depression diagnosis that resolved over time, and this group also had a significant increase in cell activity measured in lytic units during this period. CONCLUSIONS: This study suggests that depression may impair certain aspects of innate cellular immunity relevant to delaying the progression of HIV disease and that these alterations are reversible with the resolution of a depressive episode. These findings support an examination of NK cell activity in assessments of the relationship between depression and morbidity and mortality in HIV disease.

Neuropsychiatric manifestations of HIV infection and AIDS.

As the life expectancy of people living with HIV infection has increased (through recent advances in antiretroviral therapy), clinicians have been more likely to encounter neuropsychiatric manifestations of the disease. Some patients present with cognitive deficits due to an HIV-triggered neurotoxic cascade in the central nervous system. However, more patients present with a depressive spectrum disorder during the course of their illness, the underlying pathogenesis of which is not as well understood. This category of psychiatric disorders presents diagnostic challenges because of the many neurovegetative confounding factors that are present in association with HIV illness. As quality of life becomes a more central consideration in the management of this chronic illness, better awareness of these neuropsychiatric manifestations is paramount. This article reviews these clinical issues and the available psychopharmacologic treatment options.

Association of depression, CD8+ T lymphocytes, and natural killer cell activity: implications for morbidity and mortality in Human immunodeficiency virus disease.

A heightened risk of mood disorders, such as major depression, and acute depressive symptoms has been observed among HIV-seropositive individuals since the start of the AIDS epidemic, and an accumulating body of data now shows that depression may have an impact on morbidity and mortality among individuals with HIV disease. Although the specific physiologic mechanisms involved in this process have not been delineated, there is some evidence to suggest that certain components of innate immunity, including killer lymphocytes such as CD8+ T lymphocytes and natural killer cells, may represent key pathways through which depression affects HIV disease progression. This paper reviews some of the main studies examining the effects of depression on immunity and HIV disease progression and discusses the potential role of killer lymphocytes as an underlying mechanism by which depression may impact morbidity and mortality.

Association of depression with viral load, CD8 T lymphocytes, and natural killer cells in women with HIV infection.

OBJECTIVE: Clinical and epidemiology studies have implicated depression as a risk factor in the morbidity and mortality of many human diseases. This study sought to determine if depression was associated with alterations in cellular immunity variables-specifically, natural killer (NK) cells and CD8 T lymphocytes-in women with HIV infection. METHOD: Ninety-three women (63 HIV-seropositive, 30 HIV-seronegative) were studied as part of an ongoing longitudinal study conducted at two sites. Subjects underwent extensive clinical, psychiatric, and immunological evaluations. CBC counts and flow cytometry panels were conducted and NK cell activity assayed for all subjects; viral load was determined for HIV-seropositive subjects. RESULTS: The overall rate of major depression in the HIV-seropositive and HIV-seronegative women was 15.87% (N=10 of 63) and 10.00% (N=3 of 30), respectively. HIV-seropositive women had higher depressive symptom scores than did the comparison subjects (Hamilton depression scale: mean=8.62 [SD=7.26] versus mean=5.67 [SD=7.33], respectively). Both groups had similar anxiety scores. Depressive and anxiety symptoms were significantly associated with higher activated CD8 T lymphocyte counts and higher viral load levels. Major depression was associated with significantly lower natural killer cell activity, and depressive and anxiety symptom scores showed a similar correlation. CONCLUSIONS: Our findings provide the first evidence that depression may alter the function of killer lymphocytes in HIV-infected women and suggest that depression may decrease natural killer cell activity and lead to an increase in activated CD8 T lymphocytes and viral load. The rate of current major depression in these HIV-seropositive women (none of whom had current substance abuse) is approximately twice that reported for HIV-seropositive men. The rate is also consistent with studies of women with other medical illnesses and with a recent epidemiology study that associated depression with mortality in HIV-infected women with chronic depressive symptoms. Depression may have a negative impact on innate immunity. Examination of killer lymphocytes may prove useful in assessing the potential relationship between depression, immunity, and HIV disease progression in women.