Case-control study in ALS using the National ALS Registry: lead and agricultural chemicals are potential risk factors.

Objective: To identify occupational risk factors for ALS using well-characterized participants with ALS (P-ALS), sibling controls (S-controls), and matched population controls (P-controls) within the National ALS Registry. We also compared oxidative stress (OS) biomarkers between groups. Methods: P-ALS were recruited over 4 years. Demographic, socioeconomic, and medical data were ascertained from medical records and structured interviews. P-ALS were followed prospectively for 2 years or until death, whichever came sooner. S-controls and age-, sex-, race/ethnicity-, and residential location-matched P-controls were recruited over 3 years. Occupational exposure to lead and agricultural chemicals (ACs) were assigned by an occupational hygienist, blinded to case status. OS biomarkers in urine were measured. Results: P-ALS (mean age 62.8 years; 63% males) resided across the United States. Demographic and socioeconomic variables did not differ among P-ALS, S-controls, and P-controls. P-ALS were more likely to report occupations with exposure to lead (adjusted OR (aOR)=2.3, 95% CI 1.1, 4.6) and ACs (aOR = 2.4, 95% CI 1.2, 4.6) compared to pooled controls. Among those with occupations with exposure to both lead and ACs, aOR was 7.2 (95% CI 2.0, 26.1). Urinary 8-oxo-dG was significantly elevated among P-ALS (11.07 ± 5.42 ng/mL) compared to S-controls, P-controls, or pooled controls (pooled 7.43 ± 5.42 ng/mL; p < 0.0001) but was not associated with occupational exposure to either lead or ACs. Conclusions: Findings reveal increased risk of ALS diagnosis among those with occupational exposure to lead and ACs and increased OS biomarkers among cases compared to controls. OS may be an important pathogenic mechanism in ALS.

Comparison of counseling methods to promote employment for HIV+ ADULTS.

BACKGROUND: Despite improved health and during a strong job market (pre-COVID-19), a substantial proportion of HIV+ adults remained unemployed. This study sought to provide time-limited counseling to promote employment goals. OBJECTIVE: To determine whether behavioral activation (BA) or supportive counseling (SC), would be more effective in promoting vocational goals (full or part-time, paid or volunteer). METHODS: The study included two groups: those with clinically significant fatigue, who were first treated with armodafinil. Once their fatigue diminished, they were enrolled in the counseling program. Those without fatigue were enrolled directly. Both BA and SC interventions were manualized, consisting of eight individual sessions plus a follow-up. RESULTS: 116 participants entered counseling, including 87 assigned to BA and 29 to SC. Of these, 79 completed counseling or found a job by session eight. By follow-up, 51%of BA versus 41%of SC participants had found jobs, a non-significant difference either clinically or statistically. CONCLUSIONS: Multiple issues contributed to difficulty in employment, including gaps in resumes, loss of contact with former colleagues, and uncertainty about career direction. Ongoing barriers included substance use, housing instability, ambivalence about forfeiting government benefits, as well as inadequately treated depression. Success in employment for about half of participants is, in this context, a reasonable outcome.

Returning to work after fatigue treatment and counseling in HIV/AIDS.

BACKGROUND: Employment rates for people with HIV/AIDS are low, compared to the general population. One widespread barrier is fatigue, accompanied by daytime sleepiness and a lack of stamina. Previous pharmacological studies have demonstrated improvement of fatigue-related symptoms without affecting work-related goal attainmentOBJECTIVE:In this pilot study, we sought to determine whether a pharmacologic-behavioral two-phase combined approach could facilitate returning to work. METHODS: HIV+ participants with fatigue were treated with armodafinil. If energy improved, 8 sessions of biweekly manualized Behavioral Activation (BA) counseling were added to medication maintenance. Outcome was assessed on a 3-point scale along with clinician and self-ratings. RESULTS: Of the 46 participants enrolled in BA, 15 (33%) did not complete all 8 sessions: 6 got jobs so they no longer needed counseling; 4 did not like BA, and 5 dropped out for reasons such as moving away or substance use relapse. Of the 46, 29 (63%) attained their vocational goal and showed significant changes on self-report scales. CONCLUSIONS: Our integrated treatment including armodafinil plus BA counseling significantly increased the success of achieving work-related goals. The two-phase medication plus counseling program was well-tolerated by participants and the manualized BA counseling was readily applied by counselors without advanced mental health training, making the method potentially feasible in community settings.

Trauma and Growth: Impact of AIDS Activism.

INTRODUCTION: Our goal was to assess the long-term impact of AIDS activism of ACT UP/New York on the current adjustment of those who were members during its peak years (1987-1992), including assessment of trauma sequelae as well as posttraumatic growth. METHODS: A 90-minute semistructured interview and 6 validated self-report scales were administered. We relied on purposive and snowball sampling to recruit potential participants. Areas covered include demographics, ACT UP participation, and psychiatric problems. Self-report scales provided approximate diagnoses of PTSD and depression, as well as coping, optimism, and related concepts. RESULTS: Participants included 102 men (40% HIV-positive) and 23 women. Seventeen percent reported current symptoms suggesting PTSD, slightly above the range in general population studies. Symptoms consistent with depression were reported by 8% overall, with higher rates for HIV+ men. Enhanced sense of self, belief in change, and empowerment were reported by 93% of respondents, independent of concurrent PTSD or depression. CONCLUSIONS: Twenty-eight years later, ACT UP study participants recall their activist days during the AIDS epidemic as the peak experience of their lives. While some continue to have symptoms of stress and depression, most found that their activism has enriched their subsequent lives.

Depressive Symptoms and Suicidal Ideation Among Symptomatic Patients With a History of Lyme Disease vs Two Comparison Groups.

BACKGROUND: Depression has been reported in 8-45% of patients with posttreatment Lyme symptoms (PTLS), but little is known about suicidal ideation in these patients. METHOD: Depression and suicidal ideation were assessed using the Beck Depression Inventory (BDI-II). Scores from the PTLS group (n = 81) were compared to those from 2 other groups: HIV+ patients being treated for fatigue (n = 70), and a nonpatient comparison group (NPCG; n = 44). ANOVA and t-tests were used to compare groups; logistic regression was used to identify the strongest correlates of suicidal ideation. RESULTS: Mean BDI-II scores fell in the mildly depressed range for PTLS and HIV+ patients, with both groups having higher depression scores than the NPCG. Suicidal ideation was reported by 19.8% of the PTLS patients and 27.1% of the HIV+ patients, a nonsignificant difference. Among those with mild or no depression, suicidal ideation was uncommon (6.5% PTLS and 11.9% HIV+). Among the patients with moderate-to-severe depression, suicidal ideation was more common (63.2% of 19 PTLS and 50% of 28 HIV+); among these, 2 with PTLS and 1 with HIV+ expressed suicidal intent. Further, 4.5% (n = 2) of the NPCG had suicidal ideation, each had scores in the moderate-to-severe depression range. Higher scores on the cognitive symptoms subscale of the BDI-II predicted greater likelihood of suicidal ideation across patient groups. CONCLUSION: As expected, suicidal ideation is increased among patients who are depressed. The fact that 1 in 5 patients with PTLS reported suicidal ideation highlights the importance of screening for depression and suicidality to optimize patient care.

Cognitive impairment, behavioral impairment, depression, and wish to die in an ALS cohort.

OBJECTIVE: To evaluate relationships among cognitive, behavioral, and psychiatric/psychosocial measures assessed in a multicenter cohort of patients with amyotrophic lateral sclerosis (ALS). METHODS: Recently diagnosed patients with definite or probable ALS diagnosis were administered 7 standardized psychiatric/psychosocial measures, including the Patient Health Questionnaire for diagnosis of depression and elicitation of wish to die. The Cognitive Behavioral Screen was used to classify both cognitive and behavioral impairment (emotional-interpersonal function). An ALS version of the Frontal Behavioral Inventory and Mini-Mental State Examination were also administered. RESULTS: Of 247 patients included, 79 patients (32%) had neither cognitive nor behavioral impairment, 100 (40%) had cognitive impairment, 23 (9%) had behavioral impairment, and 45 (18%) had comorbid cognitive and behavioral decline. Cognitive impairment, when present, was in the mild range for 90% and severe for 10%. Thirty-one patients (12%) had a major or minor depressive disorder (DSM-IV criteria). Cognitive impairment was unrelated to all psychiatric/psychosocial measures. In contrast, patients with behavioral impairment reported more depressive symptoms, greater hopelessness, negative mood, and more negative feedback from spouse or caregiver. A wish to die was unrelated to either cognitive or behavioral impairment. CONCLUSIONS: While we found no association between cognitive impairment and depression or any measure of distress, behavioral impairment was strongly associated with depressive symptoms and diagnoses although seldom addressed by clinicians. Thoughts about ending life were unrelated to either cognitive or behavioral changes, a finding useful to consider in the context of policy debate about physician-assisted death.

Opinions of Japanese and American ALS caregivers regarding tracheostomy with invasive ventilation (TIV).

Our objective was to learn more about possible factors contributing to the higher rates of tracheostomy with invasive ventilation (TIV) for ALS patients in Japan compared with the United States by eliciting attitudes of caregivers of ALS patients in both countries. One hundred and fifty-four American caregivers from five, geographically-distributed ALS clinics and 66 Japanese caregivers from six sites in Japan completed questionnaires regarding TIV. Results showed that 33% of American caregivers were in favor of TIV for their family member compared to 53% of Japanese caregivers; 44% of American and 37% of Japanese caregivers were undecided; and 22% of American and 10% of Japanese caregivers were opposed (p <.01). Within patient-caregiver dyads, agreement in the American sample was fair, while the Japanese dyads showed poor agreement. Maintaining quality of life and patients reaching a milestone were the most common reasons for favoring TIV in the American and Japanese samples, respectively. Reasons for opposing TIV did not significantly differ. Findings suggest that caregiver preferences may influence actual choices for ALS patients. More frequent endorsement of TIV by Japanese vs. American caregivers is consistent with higher rates of TIV among Japanese patients. The results reflect the importance of caregivers' opinions in patient care.

Depression and wish to die in a multicenter cohort of ALS patients.

Our objective was to determine prevalence of depressive disorders and wish to die at the baseline visit of a longitudinal multisite study of patients with ALS. Structured telephone interviews were conducted with patients diagnosed in past 18 months at 16 U.S. ALS centers. Demographic, medical, psychiatric and other psychological measures were administered. Of 329 patients assessed, mean ALSFRS-R score was 36.6; 88% (289/329) had no depressive disorder, 7% (24/329) had minor depression, and 5% (16/329) had current major depressive disorder (DSM-IV criteria). Demographic, financial and employment factors were unrelated to depression, as were duration of ALS symptoms and respiratory status, although depressed patients had lower scores on the total ALSFRS-R (p = 0.004) and gross motor function (p < 0.001). Depressed patients reported less pleasure, greater suffering, weariness and anxiety, more stress, were less hopeful, felt less control over illness management, reported lower quality of life, more often had thoughts about ending their lives and hastening death (all p < 0.001). Of the 62 patients (19% of the sample) who expressed a wish to die, only 37% (23/62) were clinically depressed. In conclusion, depressive disorders are not necessarily to be expected of ALS patients. Wish to die is not always expressed in the context of depression and does not necessarily represent psychopathology as such.

Seeking a measure of clinically meaningful change in ALS.

We sought to identify a method to assess 'clinically meaningful change' perceived by patients, caregivers and clinical raters in relation to changes in ALSFRS-R scores at three-month intervals. In this five-site study, 81 patient-caregiver dyads were interviewed at baseline, three, and six months to assess changes in ALSFRS-R in relation to perceived occurrence of change, its magnitude and impact. Ratings by patients, caregivers and clinical raters were analyzed over three-month intervals within and between respondent groups. We found that patients, clinical raters, and caregivers agreed about 80% of the time about whether change occurred, and in what direction, on each of three visits. The perceived magnitude of change for the four domains measured by the ALSFRS-R was correlated with ratings of impact within respondent groups and across time. We also found moderate associations between changes in ALSFRS-R domain scores and judgments of symptom impact as rated by patient, caregiver and clinical rater. Independent measures (Quality of Life, Goal Assessment Scaling) showed no consistent correlations with ALSFRS-R change scores. In conclusion, the use of scales to assess the perceived magnitude and impact of change corresponding with the domains of the ALSFRS-R may be a step towards understanding of the clinical meaning of changes in that measure.

Japanese and American ALS patient preferences regarding TIV (tracheostomy with invasive ventilation): a cross-national survey.

Substantial disparities in TIV utilization rates among ALS patients have been observed, with rates in Japan far exceeding rates in the United States. Our objective was to elicit national preferences and their determinants. We predicted more Japanese than American patients would desire TIV, as would sicker patients, those already using non-invasive interventions, and those with more positive mood and outlook. Patients were enrolled in five U.S. states and six Japanese regions. Eligible patients completed surveys during clinic visits (U.S.) or at home (Japan). Survey responses were in multiple-choice format and took about 15 min to complete. One hundred and fifty-six Americans and 66 Japanese patients participated. Contrary to expectations, Japanese patients were more likely to oppose TIV, as were those on 24-h NIV and patients who knew someone using TIV. Most Japanese and American patients with advanced respiratory impairment were undecided or opposed to TIV, while nearly 20% in both countries were in favor. Finally, patients who favored TIV or who were undecided had more energy, greater wish to live, and more sense of control over ALS management. In conclusion, factors other than patient preferences, such as neurologist preferences, caregiver attitudes and perhaps lack of advance planning, may influence probability of TIV utilization.

ALS Multicenter Cohort Study of Oxidative Stress (ALS COSMOS): study methodology, recruitment, and baseline demographic and disease characteristics.

Abstract In a multicenter study of newly diagnosed ALS patients without a reported family history of ALS, we are prospectively investigating whether markers of oxidative stress (OS) are associated with disease progression. Methods utilize an extensive structured telephone interview ascertaining environmental, lifestyle, dietary and psychological risk factors associated with OS. Detailed assessments were performed at baseline and at 3-6 month intervals during the ensuing 30 months. Our biorepository includes DNA, plasma, urine, and skin. Three hundred and fifty-five patients were recruited. Subjects were enrolled over a 36-month period at 16 sites. To meet the target number of subjects, the recruitment period was prolonged and additional sites were included. Results showed that demographic and disease characteristics were similar between 477 eligible/non-enrolled and enrolled patients, the only difference being type of health insurance among enrolled patients. Sites were divided into three groups by the number of enrolled subjects. Comparing these three groups, the Columbia site had fewer 'definite ALS' diagnoses. This is the first prospective, interdisciplinary, in-depth, multicenter epidemiological investigation of OS related to ALS progression and has been accomplished by an aggressive recruitment process. The baseline demographic and disease features of the study sample are now fully characterized.

Effect of armodafinil on cognition in patients with HIV/AIDS and fatigue.

Fatigue and cognitive impairment are common in HIV+ adults and may occur independently or be causally linked. This study examined whether alleviation of fatigue with armodafinil in a placebo-controlled double-blind 4-week trial had an effect on cognitive function among those with and without mild neuropsychological impairment at baseline. Sixty-one patients completed a standard battery of neuropsychological tests at study entry and Week 4: A total of 33 were randomized to armodafinil and 28 to placebo. While there was a significant effect of active medication on fatigue, cognitive performance measured by a global change score did not differ between treatment groups, or in those on active treatment with or without mild neuropsychological impairment.

Depression and fatigue in chronic hepatitis C patients with and without HIV co-infection.

BACKGROUND: Depression and fatigue are common in chronic hepatitis C (CHC). OBJECTIVE: We report clinical predictors of these conditions in patients seen in a university clinic. METHODS: A total of 167 CHC patients completed the Patient Health Questionnaire-9 (PHQ-9) and Fatigue Severity Scale (FSS). Major depressive disorder (MDD) suggested by PHQ-9 was confirmed by clinical interview. FSS scores ≥41 were considered clinically significant fatigue. Logistic and multiple regression models were employed for analysis. RESULTS: Thirty-three percent of patients had MDD and 52% had clinically significant fatigue. Sixty-one percent were HIV-infected, among whom both MDD and clinically significant fatigue were significantly less prevalent (OR = 0.47 and 0.46, respectively). MDD was least common in patients without a history of IV drug use (OR = 0.28), and highest in methadone users (OR = 3.57). Compared with methadone users, patients with no history of IV drug use and former IV drug users had less severe fatigue (coefficients = -31.0, -34.0, respectively). Lack of a history of hepatitis treatment was also associated with less severe fatigue (coefficient= -7.6). CONCLUSION: Our study confirms high prevalence of fatigue and depression in CHC. HIV-positivity was associated with lower rates of MDD and clinically significant fatigue, arguably due to support systems for people living with HIV. Higher rates of depression in methadone users might be due to intrinsically higher rates of psychopathology in this group. Being on hepatitis treatment was associated with higher rates of fatigue, probably due to the adverse effects of interferon. Our findings emphasize the importance of routine screening and evaluation of depression and fatigue in CHC populations.

Tracheostomy with invasive ventilation for ALS patients: neurologists' roles in the US and Japan.

Our objective was to determine whether substantial differences in rates of TIV utilization in the U.S. and Japan are associated with the role of the treating neurologist. Questionnaires in English and Japanese were sent to neurologists who treated ALS patients in both countries. Questions included queries about rates of TIV use in their practices, level of encouragement of TIV use, the role of the neurologist in TIV decision making, management of patient/family requests to discontinue TIV once initiated, and personal choices if neurologists themselves had ALS. Results showed that 84% of American neurologists reported fewer than 10% of their patients had TIV, compared to 32% of Japanese. Americans less often encouraged TIV use (79% of American and 36% of Japanese seldom or never suggested or encouraged TIV). Finally, neurologists were asked whether they would choose TIV for themselves in the hypothetical scenario where they had ALS: over 70% of both groups declined TIV for themselves. In conclusion, consistent with past findings, Japanese neurologists were more likely to recommend TIV and more of their patients received TIV. Both groups believed their recommendations influence patient decisions. While Americans seldom recommended TIV to patients and most would not choose TIV for themselves, Japanese neurologists' recommendations and personal choices diverged.

DHEA and cognition in HIV-positive patients with non-major depression.

BACKGROUND: Dihydroepiandrosterone (DHEA) has been investigated for its potential role in improving cognition in a number of patient populations. Treatment options are limited for HIV-associated neurocognitive disorders. OBJECTIVE: The authors tested the effect of DHEA administration on the cognitive functioning of HIV-positive subjects with non-major depression. METHOD: The neuropsychological testing data for 60 HIV-positive patients enrolled in a clinical trial for non-major depression were analyzed to determine if DHEA-treated patients demonstrated improved cognitive functioning versus placebo. RESULTS: At baseline, 80% of the sample met criteria for asymptomatic cognitive impairment. No benefit in cognitive performance was found on 16 of 17 neuropsychological measures evaluated. One measure showed a modest benefit for placebo-treated patients over DHEA. CONCLUSION: DHEA treatment was not associated with improved cognitive performance in HIV-positive patients with non-major depression.

Gender, HIV status, and psychiatric disorders: results from the National Epidemiologic Survey on Alcohol and Related Conditions.

OBJECTIVE: More than 30 years after the onset of the human immunodeficiency virus (HIV) epidemic, there is no information on the prevalence of psychiatric disorders among HIV-positive individuals in the general population. We sought to compare the prevalence of 12-month psychiatric disorders among HIV-positive and HIV-negative adults stratified by sex and to examine the differential increase in risk of a psychiatric disorder as a function of the interaction of sex and HIV status. METHOD: Face-to-face interviews were conducted between 2004 and 2005 with participants in the National Epidemiologic Survey on Alcohol and Related Conditions Wave 2, a large nationally representative sample of US adults (34,653). The diagnostic interview used was the Alcohol Use Disorder and Associated Disabilities Interview Schedule-DSM-IV Version. RESULTS: When compared with their HIV-negative same-sex counterparts, HIV-positive men were more likely to have any mood disorder (odds ratio [OR] = 6.10; 95% confidence interval [CI], 2.99-12.44), major depressive disorder/dysthymia (OR = 3.77; 95% CI, 1.16-12.27), any anxiety disorder (OR = 4.02; 95% CI, 2.12-7.64), and any personality disorder (OR = 2.50; 95% CI, 1.34-4.67). In relation to their same-sex HIV-negative counterparts, the effect of HIV status on the odds of any mood disorder (OR = 7.17; 95% CI, 2.52-20.41), any anxiety disorder (OR = 3.45; 95% CI, 1.27-9.38), and any personality disorder (OR = 2.66; 95% CI, 1.16-6.10) was significantly greater for men than women. CONCLUSIONS: HIV status was significantly more strongly associated with psychiatric disorders in men than in women. HIV-positive men had a higher prevalence than HIV-negative men of most psychiatric disorders. By contrast, HIV-positive women were not significantly more likely than HIV-negative women to have psychiatric disorders.

Treatment of HIV-related fatigue with armodafinil: a placebo-controlled randomized trial.

OBJECTIVE: To evaluate the efficacy and safety of armodafinil in the treatment of fatigue in HIV+ patients, and to assess its effect on depressive symptoms and behavior once fatigue remitted. METHOD: HIV+ patients with clinically significant fatigue were treated in a placebo-controlled randomized double-blind trial for 4 weeks. Armodafinil responders and placebo non-responders or relapsers were treated openly for a total of 16 weeks with armodafinil. The primary outcome measure for fatigue and depression was the Clinical Global Impressions-Improvement Scale, supplemented by the Fatigue Severity Scale, the Hamilton Depression Rating Scale, and the Beck Depression Inventory. Safety was assessed with assays of CD4 cell count and HIV RNA viral load and the SAFTEE side effects rating scale. Maximum trial dose of armodafinil was 250 mg/d. RESULTS: Seventy patients were enrolled. Attrition was 9%. In intention-to-treat analyses, fatigue response rate to armodafinil was 75% and to placebo, 26%. Armodafinil did not reduce depressive symptoms in the absence of improved energy, but of those patients with an Axis I depressive disorder at study entry whose energy improved, 82% experienced improved mood as well. Markers of immunologic suppression did not change during treatment. At 6 months, those still taking armodafinil had more energy and fewer depressive symptoms than those who were no longer taking it. CONCLUSIONS: As we found in our RCT of modafinil, armodafinil appears effective and well tolerated in treating fatigue in HIV+ patients. Side effects were minimal and most patients reported substantially improved energy and mood.

Efficacy and tolerability of high-dose dronabinol maintenance in HIV-positive marijuana smokers: a controlled laboratory study.

RATIONALE: Dronabinol (Δ(9)tetrahydrocannabinol) is approved for HIV-related anorexia, yet, little is known about its effects in HIV-positive marijuana smokers. HIV-negative marijuana smokers require higher than recommended dronabinol doses to experience expected effects. OBJECTIVES: Employing a within-subjects, double-blind, placebo-controlled design, we assessed the effects of repeated high-dose dronabinol in HIV-positive marijuana smokers taking antiretroviral medication. METHODS: Participants (N = 7), who smoked marijuana 4.2 ± 2.3 days/week, resided in a residential laboratory for two 16-day stays, receiving dronabinol (10 mg QID) in one stay and placebo in the other. Efficacy was assessed with objectively verified food intake and body weight. Tolerability was measured with sleep, subjective, and cognitive assessments. For analyses, each inpatient stay was divided into two phases, days 1-8 and 9-16; we compared dronabinol's effects with placebo in each 8-day phase to investigate tolerance. RESULTS: Despite sustained increases in self-reported food cravings, dronabinol only increased caloric intake in the initial 8 days of dosing. Similarly, sleep quality was improved only in the first 8 days of dosing. Dronabinol's mood-enhancing effects were sustained across the 16-day inpatient stay. Dronabinol was well tolerated, causing few negative subjective or cognitive effects. CONCLUSIONS: In HIV-positive marijuana smokers, high dronabinol doses safely and effectively increased caloric intake. However, repeated high-dose dronabinol appeared to result in selective tolerance to these effects. These findings indicate that HIV-positive individuals who smoke marijuana may require higher dronabinol doses than are recommended by the FDA. Future research to establish optimal dosing regimens, and reduce the development of tolerance, is required.

Modafinil treatment for fatigue in HIV/AIDS: a randomized placebo-controlled study.

OBJECTIVE: To evaluate the efficacy and safety of modafinil in the treatment of fatigue in patients with human immunodeficiency virus/acquired immune deficiency syndrome (HIV/AIDS) and to assess effect on depressive symptoms. METHOD: Patients who were HIV+ and had clinically significant fatigue (according to the Fatigue Severity Scale [FSS]) were included in a 4-week randomized, placebo-controlled, double-blind trial. This was followed by an additional 8 weeks of open-label treatment for modafinil responders and 12 weeks for placebo nonresponders. The primary outcome measure for fatigue and depression was the Clinical Global Impressions-Improvement scale, supplemented by the FSS, Hamilton Depression Rating Scale, and Beck Depression Inventory. Safety was assessed with assays of CD4 cell count and HIV ribonucleic acid (RNA) viral load. Visits were weekly for 4 weeks, then biweekly, with a follow-up visit at 6 months. Maximum trial dose of modafinil was 200 mg/d. Data for this study were collected between December 2004 and December 2008. RESULTS: 115 patients were randomly assigned. In intention-to-treat analyses, fatigue response rate to modafinil was 73% and to placebo, 28%. Attrition was 9%. Modafinil did not have an effect on mood alone in the absence of improved energy. At week 4, CD4 cell counts did not change significantly; HIV RNA viral load showed a trend decline for patients taking modafinil but not for those taking placebo. At 6 months, those still taking modafinil had more energy and fewer depressive symptoms than patients who were not taking modafinil, and only those still taking modafinil showed a significant decline from baseline in their HIV RNA viral load. CONCLUSIONS: Modafinil appears to be effective and well tolerated in treating fatigue in HIV+ patients. Consideration of its use is warranted considering the high prevalence of fatigue in the HIV community, its minimal side effects, and overall patient acceptance. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00118378.