1. HIV and Mental Health: Beyond CD4 counts and viral loads Katherine R. Schafer MD Fellow, Division of Infectious Diseases and International Health University of Virginia

2. I HAVE NO DISCLOSURES OR CONFLICTS OF INTEREST TO REPORT

3. Overview HIV Epidemiology (with a focus on the South) Brief overview of HIV pathophysiology Epidemiology of mental illness in people living with HIV The impact of stress and mental health on HIV infection

4. Current State of the Union 1,178,350 people aged 13 or older are living with HIV in the U.S. – 20% of these people do not know they are positive Approximately 50000 Americans become infected each year Centers for Disease Control and Prevention

5. AIDS Diagnoses among Adults and Adolescents, by Population of Area of Residence and Region, 2010—United States http://www.cdc.gov/hiv/topics/surveillance/resources/slides /urban-nonurban/index.htm

6. Adults and Adolescents Living with an AIDS Diagnosis, by Population of Area of Residence and Region, Year-end 2009—United States http://www.cdc.gov/hiv/topics/surveillance/resources/slides /urban-nonurban/index.htm

7. New HIV Infections by State (2010) Tennessee ranked 13 th with 976 new cases www.statehealthfacts.org

8. Black/African Americans are disproportionately affected cdc.gov

9. HIV PATHOGENESIS Image from Cornell Chronicle

10. clinicaloptions.com/hiv HIV Entry and Tropism HIV Life Cycle Maturation 2. Membrane fusion & entry 9. Budding 3. Uncoating & reverse transcription 4. Nuclear uptake 5. Integration 6. Transcription & RNA processing 7. Nuclear export 8. Translation & Assembly 1. Receptor binding Adherence receptor antagonists Fusion inhibitors Reverse transcriptase inhibitors Integrase inhibitors Protease inhibitors

11. HIV in the Central Nervous System Infected monocytes and lymphocytes carry virus across blood-brain barrier Immune response to viral proteins is primary driver of neuronal damage CNS may exist as a reservoir for virus, even with undetectable plasma viral loads Antiretrovirals (ARVs) may have varying CNS penetration Question of advanced aging

12. HIV AND PSYCHIATRIC COMORBIDITIES

13. Mental Illness in HIV Major depressive disorder Adjustment disorder Bipolar affective disorder Panic disorder Alcohol/Cocaine Dependence/Polysubstance Abuse PTSD (often under diagnosed) Pain disorder with physical and psychological factors Primary Thought Disorders Personality Disorders Slide Courtesy of Gabrielle Marzani MD

14. Common factors in psychiatric patients with HIV Stigma and shame Dysfunctional family of origin Unresolved loss and cut-offs Risk factors for substance abuse and sexual acting out Desire to escape HIV reality / avoidance of treatment Secrecy Difficulty adhering to treatment Slide courtesy of Karen Ingersoll PhD

15. HIV-Associated Neurocognitive Disorders (HAND) Mind Exchange Working Group; Clin Infect Dis. (2012) Asymptomatic neurocognitive impairment (ANI) Mild neurocognitive disorder (MND) HIV-associated dementia (HAD) Severity

16. Treatment of mental illness in HIV Use caution with medications due to potential interactions with ARV therapy Certain ARVs may exacerbate psychiatric symptoms Multidisciplinary approach – communication with primary HIV provider Slide courtesy of Karen Ingersoll PhD

17. ARV Therapy may exacerbate mental illness Efavirenz (Sustiva) causes Technicolor dreams (which many people like and relate to an LSD trip), dizziness, headache, confusion, stupor, impaired concentration, agitation, amnesia, depersonalization, hallucinations, insomnia For most people these side effects resolve in 6-10 weeks, but it can continue and may worsen PTSD Can cause anxiety, depression and suicidal ideation Monitor people with a history of depression carefully Efavirenz can cause a false positive for cannabis Slide courtesy of Gabrielle Marzani MD

18. IMPACT OF MENTAL ILLNESS FOR PEOPLE LIVING WITH HIV “A strong body makes the mind strong.” “If the body be feeble, the mind will not be strong” -Thomas Jefferson

19. Case: Stigma and Denial 38 yo AAM with HIV/AIDS, depression, and a history of PCP and Hepatitis B Struggles to accept diagnosis; stops medications when feels better; does not disclose status to partners or family members.

20. Engagement in Care: More than just taking your meds Adapted from Ulett et al. 2009 Retention in Care Re-engagement in care

21. Adapted from Gardner et al. 2011 and Health Resources and Services Administration (HRSA) 19% 20% 59%

22. Epidemic of Poor Engagement Increasing reports of poor engagement in care, especially PLWH in the South. – Up to 60% of PLWH in Virginia out of care. (Dolan et al 2007) – 40% of people receiving ADAP services in South Carolina (n = 13,042) have not had a viral load measured in the previous 12 months. (Olatosi et al 2009) – 75% of ADAP-enrolled patients at a large University- based southern HIV clinic do not pick up no-cost medications frequently enough to ensure virologic suppression. (Godwin et al 2009)

23. The Consequences of Poor Engagement Decreased CD4, increased viral load  faster progression to AIDS Development of resistance mutations Untreated comorbidities (psychiatric and physiologic) Increased virologic failure(Mugavero et al. 2009) Healthcare costs for hospitalization and ER visits (Horstmann et al. 2010) Mortality (Giordano et al. 2007)

24. Engagement at UVa

25. Factors associated with poor engagement Adapted from Ulett et al. 2009 Retention in Care Re-engagement in care Older age African American race Higher baseline viral load Missed visits Higher baseline CD4 Younger age Higher baseline CD4 Substance abuse Lifetime traumatic events Depression Poor coping Limited social support Stress Uninsured status Intimate partner violence (?)

26. Definition Intimate partner violence (IPV) = “…physical, sexual, or psychological harm by a current or former partner or spouse. This type of violence can occur among heterosexual or same-sex couples and does not require sexual intimacy.”* – Not limited to cohabitating partners *Centers for Disease Control

27. IPV and Health Prevalence – Women in U.S. ~ 25% 1 – Men in U.S. ~ 4.7-16.4% (MMWR 2007) gay/bisexual men ~ 32.4% 2 IPV associated with poorer general health, depressive symptoms, and unhealthy behaviors 3-5 Physiologic associations 1.Tjaden, et al. US DOJ 2000. 2.Houston E, et al. J Urban Health 2007;84:681-90. 3.Bonomi AE, et al. J Womens Health 2007;16:987-97. 4.Campbell JC. Lancet 2002; 359: 1331-6. 5.Breiding MJ, et al. Ann Epidemiol 2008;18:538-44.

28. IPV and HIV 1,2 IPV Prevalence – HIV+ women ~ 14-67% – 23% - 53.1% of HIV+ men and women 3 Increased lifetime trauma associated with: – AIDS-related mortality – all-cause mortality in HIV+ patients – decreased adherence to ART 4 1.Leserman J, Pence BW, Whetten K, et al. Am J Psychiatry 2007;164:1707-13. 2.Campbell JC, Baty ML, et al. Int J Inj Contr Saf Promot 2008;15:221-31. 3.Siemieniuk R, et al. AIDS Patient care and STDs 2010; 24:763-770. 4.Mugavero M, Ostermann J, Whetten K, et al. AIDS Patient Care STDS 2006;20:418-28.

29. Methods Participants: HIV+ men and women from the UVA Ryan White Clinic Cross-sectional surveys to determine IPV prevalence and compare outcome data based on IPV exposure Evaluation of potential covariates – Post-traumatic stress disorder – Lifetime stressors – Depression – Substance abuse – Socioeconomic status and demographics Primary Outcomes: – CD4 count – HIV VL – Engagement in care

30. Study Population - UVA Ryan White Clinic 675 active patients from Virginia and neighboring states Demographics – 69% male – 89% ages 25-64 – 43% Black/African American – 45% identify as men- who-have-sex-with-men (MSM) Socioeconomic status – 54% at or below 100% of Federal Poverty Level – 31% uninsured – 42% use Medicare or Medicaid HIV Risk Factors – 45% MSM – 9% IV drug use – 36% heterosexual contact

31. Schafer et al.AIDS Patient Care & STDs 2012.

32. IPV exposure predicts worse HIV outcomes Schafer et al.AIDS Patient Care & STDs 2012.

33. VariableCD4<200Detectable VLHigh NSR (> 33%) RR(95% CI)P valueRR (95% CI)p valueRR (95% CI)p value IPV Exposure 3.97 (1.51- 10.42) 0.005 1.92 (1.05- 3.54) 0.035 NS Age NS 0.51 (0.30- 0.88) 0.015 NS Positive PTSD screen NS 0.31 (0.15- 0.67) 0.003 NS Overall life stressor score NS 1.07 (1.00- 1.14) 0.040 1.08 (1.01- 1.16) 0.035 Severity of Alcohol Use NS 19.40 (1.60- 234.95) 0.020 NS Multivariate Analysis – IPV Model

34. Implications of Findings IPV predicts worse outcomes for people living with HIV HIV care providers should implement routine screening for IPV – Men should be included Identifying patients with trauma exposures may allow for the development of targeted interventions to improve engagement and disease outcomes

35. Summary HIV is prevalent and the epidemic is now focused in the southeastern U.S. For PLWH, mental illness is a common comorbid condition which has both direct and indirect effects on disease outcomes Incorporating neuropsychological assessments and screening for stressors is an important element of care of PLWH

36. Thank you Rebecca Dillingham MD MPH Karen Ingersoll PhD Linda Bullock PhD RN Gabrielle Marzani-Nissen MD William Petri MD PhD UVA Ryan White clinic staff and faculty NIH Training grant #5T32AI007046-33 Study participants Dr. Norman Moore and the Department of Psychiatry at Quillen College of Medicine

37. Additional References Cruess et al. BIOL PSYCHIATRY D.G. 2003;54:307–316 Tegger et al. AIDS PATIENT CARE and STDs 2008; Volume 22, Number 3. Pence et al. J Acquir Immune Defic Syndr 2006;42:298Y306) The Mind Exchange Working Group. Clin Infect Dis; 28 Nov 2012 (epub ahead of press). Angelino A & Treisman G. Clinical Infectious Diseases 2001; 33:847–56.

38. Glossary of Abbreviations PLWH = People living with HIV ARV = Anti-retroviral ART = Anti-retroviral therapy PCP = Pneumocystis jirovecii pneumonia ADAP = AIDS Drug Assistance Program VL = viral load IPV = intimate partner violence

39. Psychotropics Interact with ARVs OlanzapineRitonavir shown to decrease levels of olanzapine up to 50% in volunteers (J Clin Pharm 2002.) Follow clinically, may need higher doses, (levels are available) RisperdoneIn theory risperdone levels may be higher if on ritonavir Start lower doses and follow clinically, look for EPS with ritonavir/indinavir. QuetiapineMay need higher doses with efavarenz and nevirapine, lower doses with PIs Follow clinically, low doses often used off label for sleep, anxiety, efavarenz induced nightmares and PTSD nightmares ZiprasidoneLevels may be increased with PIs, decreased with efavarenz Start lower doses, monitor QTC (do so with all antipsychotics) AripiprazoleLevels may be increased with PIs, decreased with efavarenz Has akathisia as common side effect in this population ClozapineAvoid with ritonavir due to levels increased/decreased HaloperidolLevels may be increased with PIs, decreased with efavarenz Lower starting levels with ritonavir co-administration Slide courtesy of Gabrielle Marzani MD