Diffusion tensor imaging of patients with HIV and normal-appearing white matter on MR images of the brain.

BACKGROUND AND PURPOSE: HIV enters the CNS early in the course of infection and produces neuropsychiatric impairment throughout the course of illness, which preferentially affects the subcortical white matter. The development of a neuroimaging marker of HIV may allow for the earliest detection of cognitive impairment. The purpose of this study was to determine whether MR diffusion tensor imaging can detect white matter abnormalities in patients who have tested positive for HIV. METHODS: Ten patients with HIV (eight men and two women; mean age, 42 years) underwent MR imaging of the brain with MR diffusion tensor imaging, which included routine fluid-attenuated inversion recovery and fast spin-echo T2-weighted imaging. Diffusion constants and anisotropy indices were calculated from diffusion tensor maps. Peripheral viral load, Centers for Disease Control staging, and cluster of differentiation 4 levels were determined. RESULTS: All patients had normal results of MR imaging of the brain, except for mild atrophy. Four of 10 patients had undetectable viral loads. These patients were receiving highly active antiretroviral therapy. The diffusion constant and anisotropy were normal. Four of 10 patients had viral loads between 10,000 and 200,000. Diffusion anisotropy in the splenium and genu was significantly decreased (P < .02). The diffusion constant of the subcortical white matter was elevated in the frontal and parietooccipital lobes (11%). Two of 10 patients had viral loads >400,000. Anisotropy of the splenium was half normal (P < .0004) and of the genu was decreased 25% (P < .002). The average diffusion constant was diffusely elevated in the subcortical white matter. CONCLUSION: Calculating the diffusion constant and anisotropy in the subcortical white matter and corpus callosum in patients with HIV detected abnormalities despite normal-appearing white matter on MR images and nonfocal neurologic examinations. Patients with the highest diffusion constant elevations and largest anisotropy decreases had the most advanced HIV disease. Patients with the lowest viral load levels, who had normal anisotropy and diffusion constants, were receiving highly active antiretroviral therapy.

Health locus of control, distress, and utilization of protease inhibitors among HIV-positive men.

OBJECTIVE: To investigate the relationship between health locus of control (HLOC), distress, and protease inhibitor (PI) utilization in gay/bisexual men in all stages of HIV illness. METHOD: A total of 173 men participating in a longitudinal study of the psychological effects of HIV illness were administered a number of psychological distress measures and the HLOC scale. The association between the HLOC subscales, distress, and PI utilization was evaluated. RESULTS: In addition to physical symptoms, the attribution of health status to chance or fate significantly predicted depressive symptoms, feelings of hopelessness, and recent life stress. Results also demonstrated a significant relationship between strong, positive beliefs in doctors and other health care professionals and PI utilization. CONCLUSION: The results of this study point to a strong association between beliefs that health status is related to chance or fate and distress. In addition, beliefs in physicians and other health care providers appear to contribute to decisions to initiate PI therapy.

Relationships among apathy, depression, and cognitive impairment in HIV/AIDS.

This study was designed to determine whether apathy is associated with neurocognitive symptoms and/or depressive symptoms in HIV/AIDS and also whether apathy is associated with patient expectancies about antiretroviral medication adherence. Seventy-five HIV+ homosexual men and 58 HIV+ women were assessed for depressive disorders and symptoms. Neuropsychological tests measured attention, concentration, learning, memory, executive function, and psychomotor speed. Other measures included Marin's Apathy Evaluation Scale, the Adherence Determinants Questionnaire, CD4 cell count, and HIV RNA viral load. Apathy was consistently related to depression and unrelated to neuropsychological impairment. Patient expectancies regarding medication adherence were unrelated to apathy when the analysis was controlled for depressive symptoms.

Diagnosis and treatment of HIV-associated neurocognitive disorders.

Although significant strides have been made in recent years in treating HIV disease with new antiretroviral medications, the management of neurocognitive disorders continues to remain a challenge. This chapter provides an overview of the current epidemiology, neuropathogenesis, clinical features, diagnosis, and treatment of the central nervous system complications of HIV infection.

Substance abuse and HIV infection.

This chapter reviews the associations between substance use, comorbid psychiatric disorders, and HIV risk behaviors; the prevalence of substance use disorders among HIV-positive individuals in treatment settings; the medical, psychiatric, and substance abuse treatment of individuals with substance use disorders and HIV infection; and finally, HIV risk reduction among substance abusers.

Psychological and physical health correlates of body cell mass depletion among HIV+ men.

OBJECTIVE: To assess whether significant body cell mass depletion related to HIV is associated with declines in physical health and psychological well-being. METHODS: As part of a 2-year prospective HIV study, semiannual assessments included measures of body composition, psychological status, and physical health. RESULTS: As measured by bioelectric impedance analysis, 58 (31%) of 187 enrolled HIV+ men had significant body cell mass depletion at some point during the study, of who 23 subsequently lost at least an additional 5% of body cell mass in the 6 months between any two consecutive study visits. This additional body cell mass depletion was associated with significant increase in fatigue, global distress and depressive symptomatology, and reduced life satisfaction. CONCLUSION: These data illuminate the importance of monitoring body weight and body cell mass, and the need for awareness of the association between malnutrition, mental health, and quality of life.

Anxiety syndromes and symptoms among men with AIDS: a longitudinal controlled study.

This 2-year longitudinal study assessed prevalence of Axis I anxiety disorders and anxiety symptoms and their relationship to manifestations of HIV illness in a sample of nonintravenous drug users. The sample included 173 homosexual men with HIV or AIDS (HIV+/AIDS) and 84 homosexual men negative for HIV or AIDS (HIV-). Data were compared with national prevalence rates to provide a framework for interpretation. No significant differences were observed. However, compared with the general population, both HIV+/AIDS and HIV- men reported more anxiety symptoms and stress. For the HIV+/AIDS group there was a positive relationship between anxiety and HIV symptoms, fatigue, and physical limitations. No changes in rates or levels of anxiety were observed in those whose immunologic markers improved or worsened over the 2 years.

Psychological effects of HAART: a 2-year study.

OBJECTIVE: The objectives of this study were to evaluate the psychological consequences of combination antiretroviral treatment in terms of mood, hope, and life satisfaction in men with symptomatic human immunodeficiency virus (HIV) infection or acquired immune deficiency syndrome and to compare those whose health improved with those whose health did not improve. METHODS: One hundred seventy-three HIV+ gay or bisexual men with symptomatic HIV illness (40% nonwhite) were evaluated semiannually in a university-affiliated research program between July 1995 and December 1997. The primary outcome measures were the Structured Clinical Interview for DSM-IV, Beck Depression Inventory, Endicott Quality of Life Enjoyment and Satisfaction Questionnaire, and Beck Hopelessness Scale. RESULTS: Psychological distress in this sample was mild to moderate at baseline. During the first 2 years that highly active antiretroviral therapy became widely available, we observed a statistically significant but clinically modest reduction in distress in the sample as a whole, with significant covariates of CD4 cell count, HIV symptoms, and social support in a mixed-effects model. Rates of clinical depression declined. However, this generalized mental health improvement was not related to individual medical improvement of markers of HIV illness progression; those classified as improved were no more likely than those who remained unimproved to report greater declines in measures of distress and hopelessness. Number of self-reported physical symptoms were directly related to distress levels. CONCLUSIONS: A cohort effect was observed, with overall psychological improvement. Physical symptoms were more strongly related to psychological distress than were laboratory markers. Consequently, those whose CD4 cell count and HIV RNA viral load reflected successful treatment were no more likely than others to be relieved of the psychological burdens of illness.

DHEA treatment for HIV+ patients: effects on mood, androgenic and anabolic parameters.

The goal of this pilot study was to evaluate the effect of dehydroepiandrosterone (DHEA) on depressed mood and fatigue in HIV+ men and women, unselected for baseline DHEA level. Secondary questions concerned treatment effects on libido and body cell mass, on serum testosterone levels, and elicitation of short-term side effects. Treatment consisted of an open-label 8-week trial using DHEA doses from 200 to 500 mg/day. Mood responders were maintained for another 4 weeks, then randomized to a double blind placebo controlled 4-week discontinuation trial. Forty-five patients, including six women, entered the trial. Of 32 week 8 completers, mood was much improved in 72%, and 81% were rated responders with respect to fatigue. Response on either parameter was unrelated to baseline serum DHEA level. Twenty-one patients entered the double blind discontinuation phase. No differences in relapse rate between placebo and DHEA groups were observed for either mood or fatigue. Body cell mass increased significantly by week 8, and this improvement was maintained throughout the double blind phase for patients in both treatment conditions. Libido increased significantly as well. DHEA therapy did not have an effect on CD4 cell count or on serum testosterone levels in men. In conclusion, DHEA may be a promising treatment for HIV+ patients with depressed mood and fatigue, although persistence of response even in placebo-treated patients during the discontinuation phase leaves unresolved questions. A parallel group double blind clinical trial is indicated as the next step to more clearly identify therapeutic efficacy.

Antidepressant treatment of depression in HIV-seropositive women.

BACKGROUND: This study aimed to assess the effectiveness of fluoxetine and sertraline in treating depressed women who are seropositive for the human immunodeficiency virus (HIV) and to document barriers to study participation. METHOD: Ambulatory HIV-seropositive women with DSM-IV depressive disorders were enrolled in an 8-week, open trial of fluoxetine (N = 21) or sertraline (N = 9) initiated at standard dosages. Outcome measures included the Clinical Global Impressions-Improvement scale (CGI), Hamilton Rating Scale for Depression (HAM-D), Beck Depression Inventory (BDI), physical function ratings, and CD4 count. RESULTS: Thirty-six women were screened for the study and 30 were enrolled. Mean age was 35.5 years and HIV risk was primarily intravenous drug use (N = 16; 53%) or heterosexual contact (N = 12; 40%). Sixteen (53%) were Hispanic, 11 (37%) were African American, and 3 (10%) were white. Mean +/- SD CD4 count was 463+/-312 cells/microL, and 30% had acquired immunodeficiency syndrome (AIDS). Eighteen women (60%) completed the trial (14 fluoxetine: dose range, 10-40 mg/day; 4 sertraline: dose range, 25-100 mg/day). Of completers, 14 (78%) were clinical responders by CGI and reduction in HAM-D > 50%. Statistically significant reductions were seen in HAM-D and BDI scores, but not in measures of physical function or CD4 count. The most frequent adverse effects were anxiety, overstimulation, and insomnia. Reasons for nonparticipation or dropout included refusal to accept antidepressants on account of negative bias, preferring psychotherapy alone, adverse effects, and relapse to illicit drugs. CONCLUSION: While HIV-seropositive women may benefit from antidepressant treatment, multiple barriers to successful treatment exist. Aggressive outreach, education, and attention to the complex psychosocial needs of HIV-seropositive women are essential components of depression treatment in this population.

The relationship between employment and neuropsychological impairment in HIV infection.

The relationship between neurocognitive impairment and employment in a cohort of 130 predominantly symptomatic individuals with HIV-1 infection was examined. Participants were classified as employed (full or part-time for pay) or unemployed (N = 64) and administered a neuropsychological test battery. When covarying for CD4 count, age, and physical limitations, the results revealed that unemployed men performed below that of employed participants on tasks of memory, set shifting-cognitive flexibility, and psychomotor speed. The results are discussed within the context of similar findings in other illnesses.

Dehydroepiandrosterone sulfate (DHEAS) and testosterone: relation to HIV illness stage and progression over one year.

This study explored associations between serum dehydroepiandrosterone sulfate (DHEAS), free and total testosterone levels, and HIV illness markers, including viral load, and the behavioral problems of fatigue and depressed mood. Subjects were 169 HIV-positive men evaluated at baseline, 6, and 12 months for levels of DHEAS, total and free testosterone, HIV RNA, CD4, HIV symptoms, opportunistic illnesses, fatigue, and depression. Men with AIDS (N = 105), compared with men with less advanced illness, had lower mean levels of DHEAS. Baseline DHEAS was positively correlated with CD4 count, HIV symptom severity, and was inversely correlated with HIV RNA. Baseline DHEAS below the laboratory reference range (96 microg/dl) was associated with history of opportunistic infections and malignancies (adjusted odds ratio [OR], 4.4; 95% confidence interval [CI], 1.9-10.4) and with incidence of these complications or death over 1 year (adjusted OR, 2.6; 95% CI, 1-7.2). Initiating protease inhibitor combination therapy was associated with an increase in DHEAS over 6 months. Free testosterone was inversely correlated with HIV RNA, but there were no other significant associations between testosterone and HIV illness markers. No hormone was related to fatigue or depression. This study confirms that low serum DHEAS is associated with HIV illness markers, including viral load, and carries negative prognostic value. Further, protease inhibitor therapy may result in increased circulating DHEAS.

Prevalence of axis I disorders in an AIDS cohort: a cross-sectional, controlled study.

The primary purpose of this study was to assess the prevalence of major psychiatric disorders in human immunodeficiency virus-positive (HIV+) men with acquired immune deficiency syndrome (AIDS)-defining conditions. Secondary goals were to identify correlates of distress and psychopathology, and to determine whether there is a gradient of distress associated with progressive HIV illness. One hundred twelve men with AIDS-defining conditions, 61 HIV+ men without AIDS, and 84 HIV-seronegative gay men were assessed. Measures included the Structured Clinical Interview for DSM-IV (SCID), Hamilton Rating Scale for Depression (HAM-D), and other dimensional measures of distress and outlook, as well as laboratory markers of HIV stage, including HIV RNA viral load assays. Rates of major depression, consistent with other findings, were in the 5% to 10% range. Mean scores on dimensional measures of distress and outlook were within the "not depressed" range and did not increase despite increasing HIV illness severity. However, rates of dysthymia were elevated among men with CD4 cell counts less than 500, and the cumulative rates of any current axis I depressive disorder for three of the four study groups were in the range of 15% to 20%. The strongest correlates of dimensional measures of distress were current HIV symptoms and social support, and to a lesser extent, a lifetime history of major depression and current use of antidepressants and/or anxiolytics. Overall, most men displayed effective adaptation to illness, but a significant minority experienced moderate psychological distress, which warrants consideration by health providers who serve this population.

Selective serotonin reuptake inhibitor treatment of depression in symptomatic HIV infection and AIDS. Improvements in affective and somatic symptoms.

Somatic symptoms often complicate the diagnosis and psychopharmacological treatment of depression in HIV illness. We treated 33 depressed HIV-positive men and women with medically symptomatic HIV or AIDS (CDC stages 2B, 2C, 3B, or 3C) in a 6 week open-label trial with sertraline, paroxetine, or fluoxetine, to assess their effectiveness and tolerability. We further assessed whether treatment of depression resulted in a reduction in both affective and somatic symptoms in this medically ill population. Twenty-four subjects (73%) completed the trial (7 on sertraline, 7 on paroxetine, 10 on fluoxetine), 20 (83%) of whom were clinical responders. Nine dropped out within 1-3 weeks of treatment because of adverse effects, mostly agitation, anxiety, and insomnia. Subjects who completed 6 weeks of SSRI treatment experienced significant reductions in both affective and somatic symptoms, many of the latter having been attributed to HIV rather than depression. These results suggest that, even in later stages of HIV illness, the contribution of depression to perceived somatic symptoms may be significant, and that these symptoms may improve with antidepressant treatment.

Psychiatric morbidity, illicit drug use and adherence to zidovudine (AZT) among injection drug users with HIV disease.

This study describes the relationship between the need for psychiatric consultation, illicit drug use, and zidovudine (AZT) adherence in HIV-infected injection drug users (IDUs) in methadone maintenance treatment (MMT). The treatment records of 57 IDUs in MMT who had been prescribed AZT between May and August of 1991 were reviewed. Those who required psychiatric consultation (P+, N = 46, 81%) were compared with those who did not require psychiatric consultation (P-, N = 11, 19%) on adherence to AZT treatment (using the mean corpuscular volume [MCV] as a biological marker), on recent illicit drug use, and on CD4 lymphocyte (T cell) count changes from the beginning to the end of AZT treatment. The P+ subjects were less likely than P- subjects to adhere to AZT treatment: fewer in the P+ group had an MCV outside of the normal range, and P+ subjects had a lower average monthly increase in MCV since the beginning of AZT treatment. Recent illicit drug use and CD4 lymphocyte count changes from the beginning to the end of AZT treatment did not show group differences. Psychiatric morbidity among HIV-infected IDUs in MMT is common, and may contribute to poor adherence to AZT treatment. Psychiatric screening and adherence-enhancing interventions should be targeted to IDUs entering drug treatment programs.

HIV-infected intravenous drug users in methadone maintenance treatment: clinical problems and their management.

Infection with the human immunodeficiency virus (HIV) is a significant and growing problem among intravenous drug users (IVDUs), both from the standpoint of personal morbidity and public health concerns regarding spread of the virus. Most HIV-infected IVDUs are opioid addicts. The most common form of long-term treatment of opioid dependence is methadone maintenance treatment (MMT). MMT can therefore play an important role in both AIDS prevention and reduction of HIV-related morbidity through diminishing drug use, promoting a healthier life-style, and providing direct medical and psychiatric care. Attempts to manage patients with a triple diagnosis of drug abuse, medical, and psychiatric problems can pose significant clinical challenges, requiring the efforts of a multidisciplinary team. The management of HIV-infected patients in MMT is discussed and case examples from the MMT program of the San Francisco General Hospital Substance Abuse Services are presented to illustrate useful strategies in the care of these complicated patients.

Adverse neuropsychiatric effects of dopamine antagonist medications. Misdiagnosis in the medical setting.

Medications with central dopamine antagonist properties are in wide use in treating a variety of medical symptoms. Some of the most commonly used are metoclopramide (Reglan), prochlorperazine (Compazine), droperidol (Inapsine), and promethazine (Phenergan). The major adverse neuropsychiatric effects seen with these medications are acute dystonias, akathisia, parkinsonian symptoms, and neuroleptic malignant syndrome. These effects are often unrecognized or misdiagnosed by the primary physician as functional psychiatric disorders. The authors present four cases in which adverse neuropsychiatric effects from metoclopramide and prochlorperazine occurred with patients in the general hospital, and they discuss their initial misdiagnosis and subsequent identification and treatment by the consulting psychiatrist. The literature is reviewed on the adverse neuropsychiatric effects of metoclopramide and prochlorperazine, with attention to patient populations at risk. The authors believe that there is a key role in this area for the consulting psychiatrist, who can provide diagnostic clarity, advice on management, and ongoing staff education.