Glenn J. Treisman

Neurologic and psychiatric complications of antiretroviral agents

Advances in highly active antiretroviral therapy (HAART) aim to improve the efficacy of HIV drugs as well as the quality of life in HIV-infected patients. Neurologic and psychologic disturbances that occur because of HIV disease and therapy are of great concern, and because they can overlap and are often difficult to distinguish, their pathogenesis is not clearly understood. Furthermore, these complications can lead to decreased adherence, thereby interfering with treatment outcomes. Antiretrovirals, including nonnucleoside reverse transcriptase inhibitors, can penetrate the central nervous system (CNS) and suppress viral replication, but they can also exacerbate CNS side effects and neuropsychiatric symptoms. When deciding which HAART drug combination is most appropriate for a patient, clinicians must consider the individuals risk of CNS complications together with the efficacy of the specific HAART regimen.

Screening for Psychiatric Morbidity in a Medical Outpatient Clinic for HIV Infection: The Need for a Psychiatric Presence

Objective: To ascertain the prevalence and type of psychiatric morbidity present in HIV infected patients presenting for the first time to a specialty HIV medical clinic. Also, to develop a way of screening for psychiatric cases in this setting using established self-report questionnaires. Method: Fifty patients who presented consecutively for medical care at the Johns Hopkins Hospital General HIV Clinic participated in this study. These patients were first screened using the General Health Questionnaire and the Beck Depression Inventory and subsequently underwent a comprehensive neuropsychiatric evaluation. Results: Fifty-four percent were found to suffer from a psychiatric disorder with an additional 22 percent from an active substance use disorder. These rates are one-and-one-half to two times higher than those reported from other medical clinics. The GHQ and BDI used together as screens could identify psychiatric “cases” with a sensitivity of 81 percent and a specificity of 61 percent, an efficacy similar to that found in other clinics. Conclusions: Given the high prevalence of psychiatric disorders in HIV infected patients presenting for medical care, screening, evaluating, and treating for these disorders is crucial and should be pursued systematically. This is best done through the presence of a psychiatric team within HIV medical clinics rather than in affiliation with such clinics.

Management of Psychiatric Disorders in Patients Infected with Human Immunodeficiency Virus

Psychiatric disorders increase the risk of acquiring human immunodeficiency virus (HIV) and increase morbidity from HIV-related illness by impeding treatment. The response to highly active antiretroviral therapies is impaired by poor patient adherence, a substantial component of which is related to mental illness and substance use disorders. The recognition of psychiatric disorders in most HIV clinics is an issue of utmost importance. We outline diagnostic and treatment issues for major depression, bipolar disorder, personality disorder, substance use disorders, and demoralization as seen in patients with HIV. Our experience at the Johns Hopkins Moore (HIV) Clinic has led us to conclude that treatment of these disorders greatly improves patient adherence to treatment and outcomes of HIV infection.

Psychiatric morbidity on entry to an HIV primary care clinic

Objective:To ascertain the prevalence and predictors of psychiatric distress in an inner-city HIV primary care clinic. Design:Cross-sectional study. Setting:Inner-city adult HIV clinic. Participants:A series of 222 HIV-infected patients newly presenting to the medical clinic for evaluation over a 1-year period. Outcome measures:A screening method, based on the General Health Questionnaire (GHQ) and the Beck Depression Inventory (BDI), whose sensitivity, specificity and positive predictive value for psychiatric diagnosis were previously established in this clinic. Results:Fifty-two per cent of participants scored above the screening threshold (i.e., scored > 14 on the BDI or > 6 on the GHQ). A comorbid substance use condition was the most powerful and consistent predictor of psychiatric distress (P < 0.05). Limited education and current unemployment contributed to higher scores on the BDI or the GHQ (P < 0.05). However, HIV illness variables and psychiatric personal or family histories were not significant predictors of psychiatric distress (P > 0.05 in all cases). Conclusions:Rates of psychiatric distress in inner-city adult HIV clinics are much higher than in the general population or than in other outpatient medical clinics. They are also not associated with what most clinicians perceive as traditional risk groups such as psychiatric histories and social disadvantage. These findings support the position that easy access to psychiatric care is essential to HIV clinics.

Major depression and demoralization in cancer patients: diagnostic and treatment considerations

Abstract. Major depression and demoralization are very common in patients with cancer. A discussion of the diagnostic specificity of major depression and demoralization (also known as adjustment disorder) is presented here, followed by a review of some effects of comorbid depression and cancer. Finally, there are a brief review of studies of antidepressant pharmacotherapy in cancer patients, a treatment algorithm for antidepressant therapy, and suggestions for treatment of demoralization.

Does the presence of a current psychiatric disorder in AIDS patients affect the initiation of antiretroviral treatment and duration of therapy

Background:Psychiatric disorders are common in HIV patients, and previous work suggests that these patients experience delays in treatment with highly active antiretroviral therapy (HAART). We investigated whether a current psychiatric disorder (1) affected the time to initiation of HAART, (2) predicted the likelihood of being prescribed HAART for at least 6 months, and (3) affected survival in urban AIDS patients. Methods:We conducted a retrospective cohort study of AIDS patients with no prior history of HAART who were enrolled and followed at the Johns Hopkins University HIV clinic between January 1996 and January 2002. Patients were stratified based on the presence of a psychiatric disorder. Cox proportional hazards regression models estimated the relative risk of receiving HAART and survival, whereas multivariate logistic regression models estimated the relative odds of remaining on HAART. Results:During the study period, 549 patients with AIDS and no prior antiretroviral treatment were enrolled in the clinic. Eighteen percent (n = 100) were defined as having a current psychiatric disorder, 39% (n = 215) were defined as having no psychiatric disorder, and 43% (n = 34) were indeterminate. Patients with a psychiatric disorder were 37% more likely to receive HAART (Cox adjusted hazard ratio [95% confidence interval (CI)]: 1.37 [1.01-1.87]), had greater than twice the odds of being prescribed HAART for at least 6 months (adjusted odds ratio [95% CI]: 2.14 [1.24-3.69]), and were 40% more likely to survive (Cox adjusted hazard ratio [95% CI]: 0.61[0.37-0.99]) as compared with those without a psychiatric disorder. Conclusion:Patients with psychiatric disorders are receiving HAART and are able to reap the survival benefit by remaining on it.

Depressive symptoms over the course of HIV infection before AIDS

The objective of this study was to describe the prevalence and course of depressive symptoms before AIDS in HIV-infected homosexual men. A descriptive and comparative analysis of data from HIV-infected and-uninfected homosexual men in the Multicenter AIDS Cohort Study was performed. The Center for Epidemiologic Studies Depression Scale (CES-D) was the primary measure of depressive symptoms. The prevalence of depressive symptoms and CES-D caseness estimates in the AIDS-free HIV-infected homosexual men were stable over time. Small differences between HIV seropositive and seronegative men were detected on the CES-D and on three of its subscales. These were mostly accounted for by less hope, and by more fearfulness, insomnia, and anorexia in the seropositive cohort. We concluded that there does not appear to be an overall increase in depressive symptoms in HIV-infected homosexual men from the time of infection until prior to AIDS. However, this group of men consistently report specific depressive symptoms more often. Implications of these findings for the clinical care of HIV-infected patients is discussed.

Interrelation between Psychiatric Disorders and the Prevention and Treatment of HIV Infection

Psychiatric disorders, particularly major depression, have a profound affect on the use of and adherence to highly active antiretroviral therapy (HAART) among patients with human immunodeficiency virus (HIV) infection. Because some of the symptoms of HIV infection are similar to those of major depression, efforts to diagnose and treat major depression are further complicated. Moreover, major depression increases vulnerability to HIV infection by provoking high-risk behaviors, and it interferes with a patients ability to comply with protocols for the prevention and treatment of HIV infection. HIV infection itself can disguise, help initiate, or exacerbate major depression. In this report, the interrelation between major depression and HIV infection is evaluated, the impact of this interrelation on adherence to HAART is described, and methods for effective treatment of psychiatric conditions in HIV-infected persons are discussed.

MOOD DISORDERS IN HIV INFECTION

Summary Major depression and mania have increased prevalence in HIV-infected patients, particularb in clinical settings and at later stages of disease. Varied rates of major depression have been reported but dzzerences in definition, methods of study, and population may partly explain these dafferences. We describe the clinical characteristics, assessment and treatment of mood disorders in HIV-infected patients, with emphasis on aspects specific to the setting of HIV infection. Diagnosis and treatment are complicated by medical complexity, stigma and psychosocial stress. Treatment is associated with clinical improvement. Mood disorders are associated with impulsivity, substance abuse, hopelessness, and demoralization, all of which may increase risk for HIV infection. Also, HIV-associated subcortical damage may be a risk factor for mood disorders, which are increased in late stage HIV infection. We discuss the data supporting the thesis that both of these factors may be at work in producing the high rates of mood disorders seen, and speculate that aggressive treatment of mood disorders may improve outcome and risk behaviors in HIV-infected patients.

Cognitive impairment in patients with AIDS - prevalence and severity.

The advent of highly active antiretroviral therapy has prolonged the life expectancy of HIV patients and decreased the number of adults who progress to AIDS and HIV-associated dementia. However, neurocognitive deficits remain a pronounced consequence of HIV/AIDS. HIV-1 infection targets the central nervous system in subcortical brain areas and leads to high rates of delirium, depression, opportunistic central nervous system infections, and dementia. Long-term HIV replication in the brain occurs in astrocytes and microglia, allowing the virus to hide from antiviral medication and later compromise neuronal function. The associated cognitive disturbance is linked to both viral activity and inflammatory and other mediators from these immune cells that lead to the damage associated with HIV-associated neurocognitive disorders, a general term given for these disturbances. We review the severity and prevalence of the neuropsychiatric complications of HIV including delirium, neurobehavioral impairments (depression), minor cognitive-motor dysfunction, and HIV-associated dementia.