Published on

Published in: Health & Medicine
1 Like
  • Be the first to comment

No Downloads
Total views
On SlideShare
From Embeds
Number of Embeds
Embeds 0
No embeds

No notes for slide
  • The Women’s Interagency HIV study (WIHS) is a prospective cohort study of women in 5 US cities (Chicago, Los Angeles, San Francisco, New York, and Washington DC). In 1994 and 1995, 2628 women were enrolled. Of these, 2059 were HIV-1 seropositive and 569 were seronegative. The first study in the table included 961 HIV-positive women with a median of 5.1 years of follow-up after the initiation of ART. Continuous HAART use strongly predicted virologic, immunologic, and clinical response. Depression was associated with poorer virologic response, immunologic failure, AIDS-defining illness, and death (all causes) Current drug use was associated with AIDS-defining illness and death from AIDS The second study in the table examined the effect of treatment for depression on adherence to ART in 1371 depressed HIV-positive women 599 (44%) of these women reported use of an antidepressant. 39% of the antidepressants were SSRIs, 26% were tricyclics, and 28% were atypicals. Antidepressant use alone was not significantly associated with use of HAART, although there was a trend (p=0.109). 923 (67%) of the women reported seeing a mental health counselor. Antidepressants plus therapy and therapy alone were both significantly associated with an increased likelihood of using HAART (P=0.009 and P=0.021, respectively). The third study in the table examined the predictors and consequences of interruption and discontinuation of HAART in 873 HIV-positive men in the Multicenter AIDS Cohort Study (MACS). Interruption of ART was predicted by younger age, black race, geographical location, higher HIV RNA level, depression, less time on ART, lower medication adherence, and not using 3TC Discontinuation of ART was predicted by younger age, higher HIV RNA level, depression, and ABC or LPV use HIV RNA increases occurred in 5% of patients who interrupted treatment for 7 or fewer days or who remained on continuous ART HIV RNA increases occurred in 37.5% of patients with longer interruptions and 70.5% who discontinued ART; these patients also experienced decreases in CD4 counts References Anastos K, Schneider MF, Gange SJ, et al; for the Women's Interagency HIV Study Collaborative Group. The association of race, sociodemographic, and behavioral characteristics with response to highly active antiretroviral therapy in women. J Acquir Immune Defic Syndr. 2005;39:537-544. Cook JA, Grey D, Burke-Miller J, et al. Effects of treated and untreated depressive symptoms on highly active antiretroviral therapy use in a US multi-site cohort of HIV-positive women. AIDS Care. 2006;18:93-100. Li X, Margolick JB, Conover CS, et al. Interruption and discontinuation of highly active antiretroviral therapy in the multicenter AIDS cohort study. J Acquir Immune Defic Syndr. 2005;38:320-328.
  • In a retrospective cohort study in Denver, 1713 HIV-positive patients were studied For more information about this study, see the Capsule Summary at
  • The Veterans Aging (VA) Cohort Study is an observational study of HIV+ and matched HIV- veterans in care at 8 sites. The study described here (n=2702) examined the association between missed doses of medication on a particular day and alcohol use 56% of the responders were abstainers (no alcohol in past 30 days), 34.5% were non-binge drinkers (alcohol in past 30 days, 4 or fewer standard drinks per day), and 8.9% were binge drinkers (at least five standard drinks on at least one day in past 30 days) Self-reported alcohol consumption was associated with missed doses Reference Braithwaite RS, McGinnis KA, Conigliaro J, et al. A temporal and dose-response association between alcohol consumption and medication adherence among veterans in care. Alcohol Clin Exp Res. 2005;29:1190-1197.
  • No changes….RSM
  • Psych

    1. 1. Psychiatric Disorders in HIV-Infected Patients Glenn J. Treisman, MD, PhD Professor Department of Psychiatry and Behavioral Sciences and Internal Medicine Director of AIDS Psychiatry Johns Hopkins University School of Medicine Baltimore, Maryland This program is supported by an educational grant from
    2. 2. About These Slides <ul><li>Users are encouraged to include these slides in their own presentations, but we ask that content and attribution not be changed. Users are asked to honor this intent. </li></ul><ul><li>These slides may not be published or posted online or used for any other commercial purpose without written permission from Clinical Care Options. </li></ul><ul><li>We are grateful to Glenn J. Treisman, MD, PhD, Johns Hopkins University School of Medicine, Baltimore, Maryland, who aided in the content creation of these slides. </li></ul>Disclaimer The materials published on the Clinical Care Options Web site reflect the views of the authors, not those of Clinical Care Options, LLC, the CME providers, or the companies providing educational grants. The materials may discuss uses and dosages for therapeutic products that have not been approved by the United States Food and Drug Administration. A qualified healthcare professional should be consulted before using any therapeutic product discussed. Readers should verify all information and data before treating patients or using any therapies described in these materials.
    3. 3. Faculty <ul><li>Glenn J. Treisman, MD, PhD Professor Department of Psychiatry and Behavioral Sciences and Internal Medicine </li></ul><ul><li>Director of AIDS Psychiatry Johns Hopkins University School of Medicine Baltimore, Maryland </li></ul>
    4. 4. <ul><li>HIV increases risk for psychiatric illness </li></ul><ul><li>Psychiatric illness increases risk for HIV </li></ul><ul><li>Effective treatment for psychiatric illness can improve patient outcome </li></ul><ul><li>Effective treatment for psychiatric illness can decrease HIV transmission </li></ul>HIV and Psychiatric Illness
    5. 5. Psychiatric Disorders Are More Prevalent in HIV-Infected Patients <ul><li>HIV Cost and Services Utilization Study (HIV-infected patients) compared with National Comorbidity Survey Replication (noninfected population) </li></ul>Bing EG, et al. Arch Gen Psychiatry. 2001;58:721-728. Burnam MA, et al. Arch Gen Psychiatry. 2001;58:729-736. Kessler RC, et al. Arch Gen Psychiatry. 2005;62:617-627. Psychiatric Disorder, % Prevalence in Survey Population HCSUS (N = 2864) NCS-R (N = 9282) Major depression 36.0 16.6 Dysthymic disorder 26.5 2.5 General anxiety disorder 15.8 5.7 Panic disorder 10.5 4.7 Any drug or alcohol use disorder 50.1 27.8
    6. 6. Mental illness Depression Demoralization Substance abuse Cognitive impairment HIV Impulsivity Depression Demoralization Substance abuse Cognitive impairment
    7. 7. Psychiatric Disorders in New Medical Intakes in an Inner-City HIV Clinic Lyketsos CG, et al. AIDS. 1996;10:1033-1039. *Treisman GJ and Hutton HH. Unpublished data. 54 Psychiatric conditions (nonsubstance use) Psychiatric Disorder, % Prevalence <ul><ul><li>Major depression </li></ul></ul>20 <ul><ul><li>Adjustment disorder </li></ul></ul>18 Substance abuse 74 Cognitive impairment 18 Personality disorder 26*
    8. 8. Differential Diagnosis for Psychiatric Disorders in Patients With HIV <ul><li>History of psychiatric disorder preceding HIV diagnosis </li></ul><ul><li>CNS HIV infection (minor neurocognitive disorder and HIV-associated dementia) </li></ul><ul><li>CNS opportunistic illnesses and cancers </li></ul><ul><li>Substance intoxication and withdrawal </li></ul><ul><li>Neuropsychiatric complications of HCV infection and its treatments </li></ul><ul><li>Neuropsychiatric side effects of HIV medications </li></ul><ul><li>Drug-drug and drug-disease interactions </li></ul><ul><li>Endocrinologic abnormalities (eg, hypogonadism, adrenal insufficiency, thyroid disease) </li></ul>
    9. 9. Depression
    10. 10. Depression <ul><li>Low mood: diminished sense of the baseline state of happiness that is usually present </li></ul><ul><li>Decreased vital sense: diminished sense of being well, healthy, energetic, alert, and able </li></ul><ul><li>Diminished self-attitude: diminished sense of being good, of doing well, of effectiveness and utility to others </li></ul><ul><li>Anhedonia: inability to experience pleasure or satisfaction in things or activities that normally produce pleasure </li></ul>
    11. 11. Depression: Disturbance of Neurophysiology <ul><li>Sleep </li></ul><ul><ul><li>Early morning awakening </li></ul></ul><ul><ul><li>Difficulty falling asleep </li></ul></ul><ul><ul><li>Disrupted sleep architecture </li></ul></ul><ul><li>Concentration </li></ul><ul><ul><li>Poor concentration </li></ul></ul><ul><ul><li>Poor memory </li></ul></ul><ul><ul><li>Difficulty producing thoughts </li></ul></ul><ul><li>Appetite </li></ul><ul><ul><li>Change in food taste </li></ul></ul><ul><ul><li>Weight loss or gain </li></ul></ul><ul><ul><li>Immune function </li></ul></ul><ul><li>Hallucinations in extreme cases </li></ul>
    12. 12. Screening for Depression <ul><li>The term “depression” is used to describe both the symptom of diminished mood but also 2 conditions (major depression and demoralization) </li></ul><ul><li>There is no confirming laboratory study for major depression </li></ul><ul><ul><li>Diagnosis is made clinically </li></ul></ul><ul><li>Screening tools were developed to track recovery from depression during treatment </li></ul><ul><li>They identify symptoms of depression but do not distinguish it from demoralization </li></ul><ul><ul><li>Clinical evaluation is therefore needed before initiating treatment for depression </li></ul></ul>
    13. 13. Screening Instruments for Patients With Depression Screening Instrument Administration Items Measurements Primary Use Beck Depression Inventory (BDI) Self-report 20 Cognitive, somatic subscales Clinical Center for Epidemiological Studies-Depression (CES-D) Self-report 20 Cognitive, somatic subscales (cut scores for clinically relevant symptoms) Epidemiologic Hamilton Rating Scale for Depression (HAM-D) Clinician 17 Affective, vegetative subscales Research Hospital Anxiety and Depression Scale (HADS) Self-report 7 Screens depression and anxiety; excludes somatic symptoms Medical Patient Health Questionnaire-9 (PHQ-9) Depression Module Self-report 9 Keyed to DSM-IV depression diagnostic criteria; also somatic symptoms, anxiety disorders, alcohol and drug abuse Primary care
    14. 14. Depression Stress Demoralization CNS inflammation Substance abuse Subcortical injury Cognitive impairment HIV Impulsivity Hopelessness Carelessness Demoralization Substance abuse Cognitive impairment
    15. 15. Depression Is Underrecognized and Undertreated in HIV-Infected Patients <ul><li>HIV-positive men in San Francisco and Denver (N = 475) </li></ul><ul><li>37% had moderate to severe depressive symptoms (CES-D ≥ 16) </li></ul><ul><ul><li>40% of depressed men received mental healthcare during previous 12 months </li></ul></ul><ul><ul><li>Only 6.3% of depressed men had received antidepressant medications during previous 12 months </li></ul></ul>Katz MH, et al. AIDS Care. 1996;8:433-442.
    16. 16. Depression and Delay in ART Initiation <ul><li>General medical practice in Boston, among patients with HIV-1 RNA > 10,000 copies/mL (N = 199) </li></ul><ul><li>In multivariate analysis </li></ul><ul><ul><li>Patients with history of depression (HR: 1.5) and history of IDU (HR: 2.7) had a delay in initiation of PI-based ART </li></ul></ul><ul><ul><li>Factors associated with earlier initiation of treatment in this population included presence of opportunistic infection (HR: 0.57 for delay of initiation) or elevated HIV-1 RNA (HR: 0.66 for delay of initiation for each 10-fold increase) </li></ul></ul>Fairfield KM, et al. J Gen Intern Med. 1999;14:446-448.
    17. 17. More Rapid Discontinuation of ART in Depressed Persons <ul><li>Depressive symptoms measured in HIV-positive patients (N = 83) by BDI </li></ul><ul><li>Less depressive: BDI < 15 (n = 50); more depressive: BDI ≥ 15 (n = 33) </li></ul><ul><li>Adherence by MEMS caps and pill counts </li></ul><ul><li>Patients with BDI ≥ 15 on HAART for longer period of time (35 months) vs those with BDI < 15 ( P = .01) but had more periods of unstructured TI ( P = .01) </li></ul><ul><li>HIV-1 RNA < 400 copies/mL in 40% of patients with BDI < 15 vs 15% of patients with BDI ≥ 15 </li></ul><ul><li>Adherence significantly greater by MEMS data (79% vs 53%; P = .02) and pill counts (66% vs 44%; P = .02) in patients with BDI < 15 </li></ul>Bangsberg DR, et al. ICAAC 2001. Abstract 1721. BDI  15 BDI < 15 Time on HAART (Mos) Cumulative Survival 1.0 70 60 50 40 30 20 10 0 0.8 0.6 0.4 0.2 0 P = .0001
    18. 18. Depression Increases Mortality in Patients on ART <ul><li>Study assessed association of depressive symptoms with HIV-related mortality and decline in CD4+ cell counts in HERS cohort (N = 765) </li></ul><ul><li>Depression (CES-D) defined as limited, intermittent, or chronic </li></ul><ul><li>Multivariate analysis: increased RR of mortality in women with chronic depressive symptoms (2.0; 95% CI: 1.0-3.8) vs those with limited or no symptoms </li></ul><ul><li>Mortality in patients with CD4+ < 200 </li></ul><ul><ul><li>Chronic depression: 54%( RR: 4.3; 95% CI: 1.6-11.6) vs limited depression </li></ul></ul><ul><ul><li>Intermittent depression: 48% (RR: 3.5; 95% CI: 1.1-10.5) vs limited depression </li></ul></ul><ul><ul><li>Limited depression: 21% </li></ul></ul>Ickovics JR, et al. JAMA. 2001;285:1466-1474. Total Time in Study (Yrs) HIV-Related Mortality Intermittent depression Chronic depression Limited depression 1.0 7 6 5 4 3 2 1 0 0.9 0.8 0.7 Cumulative Survival
    19. 19. Clinical Outcomes in Patients With Depression: WIHS and MACS Cohorts 1. Anastos K, et al. J Aquir Immmune Defic Syndr. 2005;39:537-544. 2. Cook JA, et al. AIDS Care. 2006;18:93-100. 3. Li X, et al. J Aquir Immune Defic Syndr. 2005;38:320-328. Cohort N Outcomes Predictors WIHS [1] 961 <ul><li>Virologic response </li></ul><ul><li>Immunologic response </li></ul><ul><li>Clinical response </li></ul><ul><li>Continuous use of ART </li></ul><ul><li>Absence of depression </li></ul>WIHS [2] 1371 <ul><li>Increased probability of ART utilization for women identified as depressed </li></ul><ul><li>Antidepressants + mental health therapy </li></ul><ul><li>Mental health therapy alone </li></ul><ul><li>NOT antidepressants alone </li></ul>MACS [3] 873 <ul><li>Interruption of ART </li></ul><ul><li>Age, race, geography, HIV-1 RNA, depression , time on ART, lower adherence, no 3TC </li></ul><ul><li>Discontinuation of ART </li></ul><ul><li>Age, HIV-1 RNA, depression , ABC, LPV </li></ul>
    20. 20. Treatments for Depression *Treatment for which there is randomized, controlled trial evidence of efficacy for depression in HIV-infected patients. Psychopharmacologic Treatments Tricyclic Antidepressants Other Antidepressants <ul><li>Despiramine </li></ul><ul><li>Imipramine* </li></ul><ul><li>Nortriptyline </li></ul><ul><li>Doxepin </li></ul><ul><li>Buproprion </li></ul><ul><li>Duloxetine </li></ul><ul><li>Mirtazapine </li></ul><ul><li>Nefazodone </li></ul><ul><li>Venafaxine </li></ul>SSRIs Nonconventional Agents With Antidepressant Activity <ul><li>Citalopram </li></ul><ul><li>Fluoxetine* </li></ul><ul><li>Paroxetine* </li></ul><ul><li>Sertraline* </li></ul><ul><li>Dehydroepiandrosterone (DHEA)* </li></ul><ul><li>S-adenosylmethionine (SAM-e) </li></ul><ul><li>Testosterone* </li></ul>Psychostimulants Psychotherapeutic Treatments <ul><li>Dextroamphetamine* </li></ul><ul><li>Methylphenidate* </li></ul><ul><li>Pemoline* </li></ul><ul><li>Modafinil </li></ul><ul><li>Brief supportive psychotherapy (individual) </li></ul><ul><li>Cognitive behavioral psychotherapy (group and individual) </li></ul><ul><li>Cognitive behavioral stress management (group*) </li></ul><ul><li>Interpersonal psychotherapy (individual*) </li></ul>
    21. 21. Relationship Between Antidepressant Use and Adherence to ART <ul><li>1997-2001, retrospective review </li></ul><ul><li>1713 HIV-positive patients in an urban healthcare setting </li></ul><ul><ul><li>57% of patients were depressed </li></ul></ul><ul><ul><ul><li>46% of depressed patients received antidepressant treatment </li></ul></ul></ul><ul><ul><ul><li>52% of depressed patients received ART </li></ul></ul></ul><ul><li>Antiretroviral adherence lower among depressed patients not on antidepressants ( P <.005) vs patients on antidepressants </li></ul><ul><li>Nonadherence to ART more likely in patients nonadherent to antidepressants ( P = .0019) and in patients who used alcohol ( P = .01) </li></ul>Yun LW, et al. J Aquir Immune Defic Syndr. 2005;38:432-438.
    22. 22. Practical Aspects of Treating Major Depression in Patients on ART <ul><li>No antidepressant has been shown to be clinically superior to all others </li></ul><ul><li>Make adverse effects of drugs work for you </li></ul><ul><ul><li>ie, weight gain, constipation, and sedation can sometimes be beneficial </li></ul></ul><ul><li>Because of potential drug-drug interactions, clinically monitor drugs with a large therapeutic index </li></ul><ul><ul><li>eg, SSRIs, newer atypical antidepressants </li></ul></ul><ul><li>Because of potential drug-drug interactions, monitor levels of drugs with a narrow therapeutic index </li></ul><ul><ul><li>eg, tricyclic antidepressants and lithium </li></ul></ul>
    23. 23. Selecting an Antidepressant: Potential for Drug-Drug Interactions Crewe HK, et al. Br J Clin Pharmacol. 1992;34:262-265. Nemeroff CB, et al. Am J Psychiatry. 1996;153:311-320. von Moltke LL, et al. J Clin Psychopharmacol. 1994;14:1-4. von Motkle LL, et al. Clin Pharmacokinet. 1995;20(suppl 1):33. Potent P450 blockers: Potential for strong impact on metabolism of other drugs Low P450 blockers: Likely to have little impact on metabolism of other drugs Bupropion Citalopram Mirtazapine Venlafaxine Sertraline Methylphenidate Paroxetine Fluoxetine Fluvoxamine
    24. 24. Patients Who May Need Psychiatric Consultation or Referral <ul><li>Suicidal thoughts or plan (emergency) </li></ul><ul><li>History of bipolar disorder or a history of a manic episode </li></ul><ul><li>Psychosis </li></ul><ul><li>More than 1 psychiatric disorder </li></ul><ul><li>Behavioral problems (personality disorder, self-destructive behaviors) </li></ul><ul><li>Failed more than 2 trials of antidepressant therapy </li></ul>
    25. 25. Anxiety
    26. 26. Anxiety in HIV-Infected Patients <ul><li>Anxiety disorders </li></ul><ul><ul><li>Social phobia </li></ul></ul><ul><ul><li>Agoraphobia </li></ul></ul><ul><ul><li>Generalized anxiety disorder </li></ul></ul><ul><ul><li>Panic disorder </li></ul></ul><ul><ul><li>Posttraumatic stress disorder </li></ul></ul><ul><li>May be linked to previous life trauma </li></ul><ul><li>Often comorbid with depression </li></ul>
    27. 27. Rating Scales for Anxiety <ul><li>BDI, DI, HAM-D, and Hospital Anxiety and Depression Scale also have items that query anxiety symptoms </li></ul>Screening Instruments Administration Items Use Hamilton Rating Scale for Anxiety (HAM-A) Clinician rating 14 Psychopharmacology research Patient Health Questionnaire, Anxiety Module Self-report 5 Clinical: assesses generalized anxiety, panic disorder, agoraphobia State-Trait Anxiety Inventory (STAI) Self-report 20 Clinical: assesses inherent (trait) and current (state) anxiety symptoms
    28. 28. Psychiatric Disorders and Nonadherence to ARVs *Adjusted for sex, race, age, education, employment, insurance, CD4+ cell count nadir, HIV status, ART, having a case manager. Tucker JS, et al. Am J Med. 2003;114:573-580. Disorder Odds Ratio* P Value Generalized anxiety disorder 2.4 (1.2-5.0) .02 Panic disorder 2.0 (1.4-3.0) < .001 Any psychiatric disorder 1.9 (1.4-2.6) < .001 Depression 1.7 (1.3-2.3) .001 Multiple disorders (OR per disorder) 1.4 (1.3-1.5) < .001 Dysthymia 1.3 (0.9-1.9) .17
    29. 29. Treatment for Anxiety <ul><li>Psychotherapy </li></ul><ul><ul><li>Including relaxation and stress-reduction techniques </li></ul></ul><ul><li>Pharmacotherapy: must monitor for adverse effects, risk of overdose, drug interactions </li></ul><ul><ul><li>SSRIs </li></ul></ul><ul><ul><li>TCAs </li></ul></ul><ul><ul><li>Trazodone </li></ul></ul><ul><ul><li>Benzodiazepines </li></ul></ul>
    30. 30. Mania
    31. 31. Mania in HIV-Infected Patients <ul><li>Can occur in conjunction with bipolar disorder or HIV infection of the brain </li></ul><ul><li>HIV-associated mania different from mania with bipolar disorder </li></ul><ul><ul><li>Late, secondary affective disorder </li></ul></ul><ul><ul><li>Associated more often with personal or family history of mood disorder </li></ul></ul><ul><ul><li>More irritability, less hypertalkativeness, more psychomotor slowing and cognitive impairment </li></ul></ul>
    32. 32. Mania HIV High-risk behaviors
    33. 33. Extroversion May Affect Adherence and Risk Behaviors <ul><li>Consequence insensitive </li></ul><ul><li>More vulnerable to risk behaviors </li></ul><ul><li>More vulnerable to substance abuse </li></ul><ul><li>Barriers to treatment </li></ul><ul><ul><li>Impulsivity </li></ul></ul><ul><ul><li>Focus on feelings </li></ul></ul><ul><ul><li>Focus on now </li></ul></ul>
    34. 34. Treatments for HIV-Associated Mania: Guideline Recommendations <ul><li>Acute episode </li></ul><ul><ul><li>Lithium + antipsychotic </li></ul></ul><ul><ul><li>Valproic acid + antipsychotic </li></ul></ul><ul><li>Maintenance </li></ul><ul><li>Medications </li></ul><ul><ul><li>Lithium </li></ul></ul><ul><ul><li>Valproic acid </li></ul></ul><ul><ul><li>Lamotrigine </li></ul></ul><ul><ul><li>Carbamazepine </li></ul></ul><ul><ul><li>Oxcarbazepine </li></ul></ul><ul><li>Discontinue antipsychotic unless continuing psychosis or prophylaxis for recurrence </li></ul><ul><li>Psychotherapy </li></ul>Work Group on Bipolar Disorder. Available at Accessed January 9, 2008.
    35. 35. Substance Abuse
    36. 36. Substance Abuse in HIV-Infected Populations <ul><li>10% of HIV-infected patients worldwide are IDUs [1] </li></ul><ul><li>20% of adults living with HIV/AIDS in the US in 2005 contracted the disease through injection drug use [2] </li></ul><ul><li>53% of HIV-infected patients in the US had used alcohol in the previous month [3,4] </li></ul><ul><ul><li>8% were classified as heavy drinkers and 15% had at least 5 drinks on 1 occasion in the previous week </li></ul></ul><ul><li>Dangerous alcohol use also reported in developing countries [5,6] </li></ul><ul><li>Aceijas C, et al. AIDS. 2004;18:2295-2303. </li></ul><ul><li>CDC. Accessed January 11, 2008. </li></ul><ul><li>Galvan FH, et al. J Stud Alcohol. 2002;63:179-186. </li></ul><ul><li>Turner BJ, et al. J Gen Intern Med. 2001;16:625-633. </li></ul><ul><li>Shaffer DN, et al. East Afr Med J. 2004;81:594-598. </li></ul><ul><li>Mbulaiteye SM, et al. Int J Epidemiol. 2000;29:911-915. </li></ul>
    37. 37. New HIV Infections Related to Drug Abuse <ul><li>Newly diagnosed HIV/AIDS cases resulting from IDU in US in 2005 (last year for which complete results are available) </li></ul>33 17 24 29 30 0 10 20 30 40 50 30 Whites Blacks New Cases of HIV/AIDS (%) Hispanics Centers for Disease Control and Prevention. Available at: resources/reports/2005report. Accessed January 9, 2008. Females Males* *Includes MSM who are IDUs.
    38. 38. Issues Affecting ARV Adherence for Substance Abusers <ul><li>Instability of lifestyle </li></ul><ul><ul><li>Housing, poverty </li></ul></ul><ul><li>Lack of social support </li></ul><ul><li>Mistrust of the medical system </li></ul><ul><li>Clinician discomfort with treating IDUs </li></ul><ul><li>Immediate needs of addiction outweigh long-term health needs </li></ul><ul><li>Medical complications related to addiction (infections, poor nutrition) </li></ul><ul><li>Hepatitis C coinfection </li></ul>O'Connor PG, et al. N Engl J Med. 1994;331:450-459.
    39. 39. Drug Use and Clinical Outcomes <ul><li>Prospective study (interview) of Hopkins cohort (N = 764) of patients with nadir CD4 + lymphocyte count < 500 cells/mm ³ or a peak HIV-1 RNA > 30,000 copies/mL </li></ul><ul><li>Adherence, virologic, and immunologic outcomes deteriorated among current IDUs </li></ul>P < .05 Lucas G, et al. J Aquir Immune Defic Syndr. 2001;27:251-259. P < .001 Former users Nonusers Active users Change in HIV-1 RNA -1.7 -1.6 -0.8 † Patients Reporting Nonadherence (%) Nonadherence CD4+ Count Increase 24 17 34 116 122 65* 0 10 20 30 40 50 P = .11 Change in CD4+ Count (cells/mm ³) 25 50 75 100 125 Change HIV RNA-1 (log 10 copies/mL) -2.0 -1.5 -1.0 -0.5 * P = .003 vs nonusers and former users; P < .001 vs nonusers and former users. -2.5 0 0
    40. 40. Alcohol Consumption and Adherence <ul><li>Temporal and dose-response association </li></ul>Braithwaite RS, et al. Alcohol Clin Exp Res. 2005;29:1190-1197. Veterans Aging Cohort Study HIV-positive and matched HIV-negative respondents (N = 2702) Binge drinkers: 8.9% (n = 239) Nonbinge drinkers: 34.5% (n = 931) Abstainers: 56.6% (n = 1582) Missed doses on 2.4% of all days surveyed Drinking days: 3.5% Postdrinking days: 3.1% Nondrinking days: 2.1% ( P < .001 for trend) Trend stronger for HIV+ Drinking days: 11% Postdrinking days: 7.0% Nondrinking days: 4.1% ( P < .001 for trend) Trend comparable for HIV+ and HIV- Missed doses
    41. 41. Attributes Associated With Poor Adherence by Healthcare Providers <ul><li>Attribute Prescribers Associating Attribute With Poor Adherence, % </li></ul><ul><li>Active alcohol abuse 93.1 </li></ul><ul><li>Active injection drug use 92.5 </li></ul><ul><li>Homelessness 88.1 </li></ul><ul><li>Depression 69.2 </li></ul><ul><li>History of injection drug use 52.9 </li></ul><ul><li>History of alcohol abuse 43.4 </li></ul><ul><li>Motherhood of small children 38.1 </li></ul><ul><li>Lower educational level 37.0 </li></ul><ul><li>Lower income level 15.8 </li></ul><ul><li>Minority race 11.4 </li></ul>Stone V, et al. Curr HIV/AIDS Rep. 2005;2:189-193 .
    42. 42. Coordinated Medical Care for Substance Abusers Improves Outcome <ul><li>Patients receiving directly observed ART (N = 72) in a variety of healthcare services </li></ul><ul><li>Study aimed to assess impact of colocated medical, case management, and referral to substance abuse services in subjects receiving directly observed therapy </li></ul><ul><li>Primary outcome: virologic success, defined as HIV-1 RNA < 400 copies/mL or > 1.0 log 10 copies/mL reduction </li></ul><ul><li>In multivariate analyses, virologic success at 6 months associated with high medical services utilization and use of case management services </li></ul><ul><li>Referral to off-site substance abuse services treatment not associated with either virologic outcome </li></ul>Smith-Rohrberg D, et al. J Aquir Immune Defic Syndr. 2006;43:S48-S53. Parameter at Mo 6 Virologic Success Mean HIV-1 RNA Reduction (log 10 c/mL) Adjusted OR (95% CI) P Value Difference in Slope From BL P Value Colocated medical services utilization 10.1 (1.3-79.0) .03 -0.9 (-1.7 to -0.2) .02 Case management services 6 (1.2-32.1) .04 -1.0 (-1.8 to -.0.2) .02
    43. 43. Serious Mental Illness
    44. 44. Serious Mental Illness and HIV Infection in a Medicaid Population <ul><li>Medicaid claims data and welfare recipient files for persons 18 years of age or older for fiscal years 1994-1996 in Philadelphia (N = 391,454) </li></ul><ul><li>Patients with diagnosis of serious mental illness 5-fold more likely to have HIV diagnosis, after adjusting for age, sex, time on welfare [1] </li></ul><ul><li>High rate seemed to be driven by high-risk behavior </li></ul><ul><li>Interventions aimed at risk reduction in this population (including education, condom use, assertiveness training) have met with limited success [2] </li></ul>1. Blank MB, et al. Psychiatr Serv. 2002;53:868-873. 2. Johnson-Masotti AP, et al. J Ment Health Policy Econ. 2003;6:23-35. Mental Illness OR of Concomitant HIV Diagnosis 95% CI Schizophrenia 1.51 0.45-3.56 Affective disorder 3.84 3.76-3.91
    45. 45. Issues Related to Antiretroviral Drugs
    46. 46. Psychiatric Complications of Antiretroviral Agents <ul><li>CNS effects of efavirenz demonstrated in cohorts, clinical studies </li></ul><ul><ul><li>Up to 50% of patients in clinical studies experience dizziness, headache, confusion, impaired concentration, and abnormal or vivid dreams </li></ul></ul><ul><ul><ul><li>Usually resolve in 2-4 weeks [1,2] </li></ul></ul></ul><ul><ul><li>Severe psychiatric symptoms reported in small percentage of patients in clinical trials </li></ul></ul><ul><ul><li>Current practice indicates close monitoring in EFV-treated patients with current or history of psychiatric illness; EFV not contraindicated </li></ul></ul><ul><li>Case reports with other agents </li></ul><ul><ul><li>Zidovudine: mania, depression, insomnia, headaches [3-5] </li></ul></ul><ul><ul><li>Abacavir: psychosis [6,7] </li></ul></ul><ul><ul><li>Nevirapine: psychosis [8] </li></ul></ul>1. Sustiva [package insert]. Princeton, NJ: Bristol-Myers Squibb; January 2007. 2. Clifford DB, et al. Ann Intern Med. 2005;143:714-721. 3. Maxwell S, et al. JAMA. 1988;259:3406-3407. 4. O’Dowd MA, et al. JAMA. 1988;260: 3587. 5. Schaerf FW, et al. JAMA. 1988;260:3587-3588. 6. Colebunders R, et al. Am J Med. 2002;113:616. 7. Foster R, et al. AIDS. 2004;18:2449. 8. Wise ME, et al. BMJ. 2002:324:879.
    47. 47. Psychiatric Agents Contraindicated With Antiretroviral Agents Anxiolytics Agent Interacting Antiretroviral Effect Antidepressants St John’s wort All ARVs ARV ↓ Alprazolam DLV Alprazolam ↑ Midazolam All PIs, DLV, EFV Midazolam ↑ Triazolam All PIs, DLV, EFV Triazolam ↑ Antipsychotics Pimozide All PIs, DLV Pimozide ↑
    48. 48. Psychiatric Agents That Require Dose Adjustment With ARVs Olanzapine dose may need increasing; monitor and adjust as necessary <ul><li>Olanzapine AUC ↓ </li></ul>RTV Olanzapine Antipsychotic Agent Monitor bupropion for therapeutic efficacy; bupropion dose may need to be increased <ul><li>Bupropion AUC ↓, C max ↓ </li></ul><ul><li>LPV/RTV unchanged </li></ul>LPV/RTV Bupropion Agent ARV Effect Recommendation Antidepressants Paroxetine DRV/RTV <ul><li>Paroxetine AUC↓, C max ↓, C min ↓ </li></ul><ul><li>DRV unchanged </li></ul>Titrate paroxetine to therapeutic effect Sertraline DRV/RTV <ul><li>Sertraline AUC ↓, C max ↓, C min ↓ </li></ul><ul><li>DRV unchanged </li></ul>Titrate sertraline to therapeutic effect Trazodone RTV <ul><li>Trazodone AUC ↑, C max ↑ </li></ul>↓ Trazodone dose by 50% with slow-dose titration
    49. 49. Psychiatric Agents That Require Dose Adjustment With ARVs (cont’d) Monitor for toxicity such as increased sedation; decrease dose or use lorazepam <ul><li>Oxazepam ↑ </li></ul>DLV Oxazepam Administer alprazolam at lowest possible dose with slow titration <ul><li>Alprazolam clearance ↓, AUC ↓ </li></ul>RTV Alprazolam Recommendation Effect ARV Agent Anxiolytic Agents Lamotrigine LPV/RTV <ul><li>Lamotrigine ↓ </li></ul>May need to increase lamotrigine with coadministration Phenytoin LPV/RTV <ul><li>Lopinavir AUC ↓ </li></ul><ul><li>Phenytoin AUC ↓ </li></ul>↑ LPV/RTV to 600/150 mg BID (tablets) or 533/133 mg BID (capsules), along with TDM; monitor anticonvulsant levels; do not use QD LPV/RTV Mood Stabilizers Carbamazepine EFV <ul><li>EFV AUC ↓, Cmax ↓, C min ↓ </li></ul><ul><li>Carbamazepine AUC ↓, C max ↓, C min ↓ </li></ul>Monitor carbamazepine levels and EFV C min
    50. 50. Psychiatric Agents That Require Dose Adjustment With ARVs Recommendation Effect ARV Agent Opiates Buprenorphine ATV <ul><li>Buprenorphine AUC ↑, C min ↑ </li></ul>Monitor for increased sedation; consider buprenorphine dose reduction Buprenorphine RTV <ul><li>Buprenorphine AUC ↑ </li></ul>Monitor for increased sedation; consider buprenorphine dose reduction Methadone DRV/RTV <ul><li>R-methadone ↓ </li></ul><ul><li>S-methadone ↓ </li></ul>↑ Methadone dose Methadone LPV/RTV <ul><li>R-methadone AUC ↓ </li></ul>May need to ↑ methadone dose in a small subset of patients Methadone EFV <ul><li>R-methadone AUC ↓ </li></ul>Monitor for opiate withdrawal; may need to increase maintenance dose of methadone Methadone NVP <ul><li>R-methadone AUC ↓ </li></ul>Monitor for opiate withdrawal; may need to increase maintenance dose of methadone
    51. 51. Psychiatric-ARV Interactions With Undefined Clinical Significance Anxiolytics Midazolam AUC ↑ 18% MVC Midazolam Desipramine AUC ↑ RTV Desipramine Effect ARV Agent Antidepressants Fluoxetine DLV DLV C min ↑ Fluoxetine RTV RTV AUC ↑ Fluoxetine NVP Fluoxetine AUC ↓ Paroxetine FPV Paroxetine AUC ↓ Sertraline EFV Sertraline AUC ↓, C max ↓, C min ↓ Mood Stabilizer Valproic acid LPV/RTV LPV/RTV AUC ↑ (nonsignificant)
    52. 52. Psychiatric-ARV Interactions With Undefined Clinical Significance (cont’d) Effect ARV Agent Opiates Buprenorphine EFV Buprenorphine AUC ↓, C min ↓ Methadone ddI ddI AUC ↑; R-methadone not affected Methadone d4T d4T AUC ↓; R-methadone not affected Methadone APV R-methadone AUC↓ 13%; S-methadone AUC ↓ 37% Methadone NFV S-methadone AUC ↓; R-methadone AUC not affected Methadone RTV R-methadone AUC ↓ 36%; S-methadone AUC ↓ 25% Methadone SQV R-methadone AUC ↓ 20%
    53. 53. <ul><li>2 CME-Certified Modules </li></ul><ul><li>3 CME-Certified Interactive Case Challenges </li></ul><ul><li> </li></ul>Go Online for More Information About Psychiatric Patients With HIV