Judith G. Rabkin

Highly active antiretroviral treatment in Hiv infection: benefits for neuropsychological function

Objectives:To determine whether highly active antiretroviral therapy (HAART) is associated with reduced HIV-associated neuropsychological impairment. Design:Cross-sectional analysis in a natural history study of adaptation to HIV/AIDS. Method:A sample of 130 homo-/bisexual men with HIV/AIDS (mean age, 41 years; 42% non-white) were evaluated with a neuropsychological battery assessing attention, concentration, psychomotor speed, learning, memory and executive function. Subjects taking HAART were compared with those not taking HAART on demographics, CD4 cell count, viral load, scores on individual neuropsychological tests and proportion with neuropsychological impairment. Results:Sixty-nine (53%) subjects were taking HAART, and 48 (37%) were neuropsychologically impaired. Subjects taking HAART had lower mean CD4 cell counts than those not taking HAART (254 versus 342 × 106/l; P < 0.05), although they were more likely to have undetectable viral load (42 versus 20%; P < 0.01) and were less likely to be neuropsychologically impaired (22 versus 54%; P < 0.0001). Subjects taking HAART performed significantly better on tests of attention, concentration, learning, memory, and psychomotor speed. After excluding subjects with potential non-HIV confounders of neuropsychological function, those without neuropsychological impairment had significantly lower mean viral load levels and were more likely to have undetectable viral load than those with impairment. Conclusion:These preliminary findings suggest that HAART benefits neuropsychological function through the reduction of viral load.

Evaluation of seasonality in six clinical populations and two normal populations

The Seasonal Pattern Assessment Questionnaire (SPAQ) was used to evaluate retrospectively self-reported seasonal changes in mood and behavior (seasonality) of two normal and six clinical populations: patients with winter-seasonal affective disorder (SAD), summer-SAD, eating disorders, bipolar affective disorder, major depressive disorder and subsyndromal winter-SAD. The SPAQ successfully discriminated between groups expected to have high seasonality scores, such as winter-SAD, summer-SAD and subsyndromal winter-SAD, and normal controls. Bipolars and major depressives had normal seasonality scores. Patients with eating disorders had unexpectedly high scores. There was a general tendency for all groups to eat and sleep more and to gain weight in the winter. The implications of these findings are discussed.

Measuring medication adherence: Are missed doses reported more accurately than perfect adherence?

Self-reports overestimate adherence compared to more objective measures such as electronic monitoring. However, self-report is the most feasible method for clinical settings; therefore, it is important to identify the context in which this method can provide an accurate assessment. To address whether self-reports are more accurate when missed doses are reported, we conducted a secondary analysis of data from a methodological study comparing multiple measures of adherence (including self-report and electronic monitoring) to a two-week placebo regimen mimicking HAART among 30 HIV-positive patients not on HAART. Results indicated a mean adherence of 85% and 62%, as measured by self-report and electronic monitoring, respectively. Self-report and electronic monitoring were not significantly correlated in the measurement of proportion of prescribed doses taken among the sub-group of 17 patients who reported missed doses (r = 0.22), nor among those who reported no missed doses, or the group as a whole. Using electronic monitoring as the validity criterion, these findings indicate that self-reports overestimate adherence even among patients who report missed doses.

Psychopathology in male and female Hiv-positive and negative injecting drug users: longitudinal course over 3 years

Objective:To evaluate the impact of HIV illness on psychiatric and psychosocial functioning over 3 years in a sample of male and female HIV-positive injecting drug users (IDU), with a comparison group of HIV-negative male and female IDU. Design:As part of a multidisciplinary study, 121 men (69 HIV-positive, 52 HIV-negative) and 66 women (36 HIV-positive, 30 HIV-negative) were evaluated semiannually for seven visits. Attrition, unrelated to sex or serostatus, was 33%. Results:At baseline, rates of major depression and dysthymia ranged from 15% (HIV-negative men) to 33% (HIV-positive men and HIV-negative women). Global impairment was in the range found in psychiatric patients (mean Global Assessment of Functioning scores, 46–51). Higher levels of social support and less social conflict were independently associated with decreased distress and improved global functioning among both men and women. For both HIV-positive groups, degree of improvement over time was related to degree of HIV progression: those who remained healthier in terms of CD4 count and illness stage showed more improvement. HIV-seronegative status was associated with less distress for men but not for women. Overall, women reported higher levels of psychiatric distress than men. Conclusions:High rates of psychopathology were found in this IDU cohort, independent of HIV status and sex. Although rates of psychopathology, injecting drug use and distress declined slightly during the study, they remained elevated; accordingly, psychiatric services are indicated for this population.

Wish to die in end-stage ALS

Background: In retrospective studies, estimates of hastened dying among seriously ill patients range from <2% in one national survey to as much as 20% in end-stage disease cohorts. Objective: To examine, in prospective studies, dying patients in the months before death, in order to understand the wish to die. Methods: Patients with advanced ALS with a high likelihood of death or need for tracheostomy within 6 months were identified. Patients were assessed monthly with an extensive psychosocial interview, including a diagnostic interview for depression. Family caregivers were interviewed on the same schedule and also after patient deaths. Results: Eighty patients with ALS were enrolled, 63% of eligible patients; 53 died over follow-up. Ten (18.9%) of the 53 expressed the wish to die, and 3 (5.7%) hastened dying. Patients expressing the wish to die did not differ in sociodemographic features, ALS severity, or perceived burden of family caregivers. They were more likely to meet criteria for depression, but differences were smaller when suicidality was excluded from the depression interview. Patients who expressed the wish to die reported less optimism, less comfort in religion, and greater hopelessness. Compared with patients unable to act on the wish to die, patients who hastened dying reported reduction in suffering and increased perception of control over the disease in the final weeks of life. Conclusion: These findings suggest caution in concluding that the desire to hasten dying in end-stage disease is simply a feature of depression.

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.

Testosterone replacement therapy in HIV illness

The purpose of this study was to determine whether testosterone replacement therapy ameliorates sexual dysfunction and associated problems of mood, energy, and appetite in HIV+ men with immune suppression (CD4 < 400 cells/cu mm) and low levels of serum testosterone. Assessments at study baseline and endpoint included psychiatric evaluation using the Structured Clinical Interview for DSM-III-R, the Hamilton Rating Scale for Depression, Clinical Global Impressions Scale, the Karnofsky Performance Index, and a side-effects rating scale. Eighty-one men entered treatment and 72 completed at least 8 weeks. At study entry, 84% had an AIDS-defining condition (1993 CDC Criteria). In terms of sexual interest and function, 85% of study completers were clearcut responders at week 8. Mood response was also good: of the 44 study completers who had mood problems at baseline, 28 (64%) were rated as much improved. Mean change in CD4 cell count after treatment was not statistically significant. These findings suggest that testosterone replacement therapy should be considered for men with immune suppression and low testosterone levels who complain of diminished sexual desire and/or dysfunction. Replication with a placebo component is indicated.

Dronabinol and marijuana in HIV-positive marijuana smokers. Caloric intake, mood, and sleep.

Objectives:Individuals with HIV constitute the largest group using cannabinoids for medicinal reasons; yet, no studies have directly compared the tolerability and efficacy of smoked marijuana and oral dronabinol maintenance in HIV-positive marijuana smokers. This placebo-controlled within-subjects study evaluated marijuana and dronabinol across a range of behaviors: eating topography, mood, cognitive performance, physiologic measures, and sleep. Methods:HIV-positive marijuana smokers (n = 10) completed 2 16-day inpatient phases. Each dronabinol (5 and 10 mg) and marijuana (2.0% and 3.9% Δ9-tetrahydrocannabinol [THC]) dose was administered 4 times daily for 4 days, but only 1 drug was active per day, thereby maintaining double-blind dosing. Four days of placebo washout separated each active cannabinoid condition. Results:As compared with placebo, marijuana and dronabinol dose dependently increased daily caloric intake and body weight in HIV-positive marijuana smokers. All cannabinoid conditions produced significant intoxication, except for low-dose dronabinol (5 mg); the intoxication was rated positively (eg, “good drug effect”) with little evidence of discomfort and no impairment of cognitive performance. Effects of marijuana and dronabinol were comparable, except that only marijuana (3.9% THC) improved ratings of sleep. Conclusions:These data suggest that for HIV-positive marijuana smokers, both dronabinol (at doses 8 times current recommendations) and marijuana were well tolerated and produced substantial and comparable increases in food intake.

TESTOSTERONE THERAPY FOR HUMAN IMMUNODEFICIENCY VIRUS-POSITIVE MEN WITH AND WITHOUT HYPOGONADISM

This study was designed to evaluate the safety and effectiveness of testosterone therapy for clinical symptoms of hypogonadism (low libido, low mood, low energy, loss of appetite/weight) in human immunodeficiency virus-positive men with CD4 cell counts less than 400 cells/mm3 and deficient or low normal serum testosterone levels. The trial consisted of 8 weeks of open treatment with 400 mg of intramuscular testosterone cypionate biweekly. Responders were maintained at this dosage for another 4 weeks and then were randomized in a double-blind, placebo-controlled, 6-week discontinuation trial. Of the 112 men who completed at least 8 weeks of treatment, 102 (91%) were rated as responders on a global assessment of sexual desire/function. Of the 34 study completers with major depressive disorder and/or dysthymia, 79% reported significant improvement in mood at week 8. Average weight change was a gain of 3.7 pounds, with 45% gaining more than 5 pounds. Eighty-four men entered and 77 completed the double-blind phase; of these, 78% of completers randomized to testosterone and 13% randomized to placebo maintained their response. No significant medical or immunologic adverse effects were identified. Testosterone therapy was well tolerated and effective in ameliorating symptoms of clinical hypogonadism, and equally so for men with and without testosterone deficiency. For patients with major depression and/or dysthymia, improvement was equal to that achieved with standard antidepressants.

Fatigue in Hiv Illness: Relationship to Depression, Physical Limitations, and Disability

Objective This study was conducted to investigate the prevalence of clinical fatigue reported by gay/bisexual men at all HIV illness stages, and whether fatigue, while associated with depression, independently contributes to limitations in physical function and disability. Method HIV- men, HIV+ men with CD4 counts >500, HIV+ men with CD4 counts 200 to 500, and men with AIDS were compared on prevalence of clinical fatigue, as defined by a standardized instrument. Among HIV+ men, the relationships among fatigue, depressed mood, major depressive disorder, HIV illness markers (including CD4 count and HIV RNA viral load), physical limitations, and disability were assessed at baseline and after 1 year. Results The prevalence of clinical fatigue in men with CD4 counts <500 was 14%, significantly higher than HIV- men and HIV+ men with CD4 counts >500. However, fatigue was not directly correlated with CD4 count or HIV RNA. Fatigue was a chronic symptom that was associated with depressed mood, major depressive disorder, physical limitations, and disability. After 1 year, an increase in depressive symptoms predicted a small amount of variance in fatigue; however, depressive symptoms were not associated with physical limitations or disability after controlling for fatigue. Conclusion Fatigue is a chronic symptom that is more prevalent in advanced HIV illness, and which, although associated with depression, does not seem to be merely a symptom of depression. Because fatigue contributes independently to physical limitations and disability, it should be assessed and treated.