HIV and Mental Health: Beyond CD4 counts and viral loads

Katherine R. Schafer MDFellow, Division of Infectious Diseases and

International HealthUniversity of Virginia

I HAVE NO DISCLOSURES OR CONFLICTS OF INTEREST TO REPORT

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

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

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

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

New HIV Infections by State (2010)

Tennessee ranked

13th with

976 new cases

www.statehealthfacts.org

Black/African Americans are disproportionately affected

cdc.gov

Image from Cornell Chronicle

HIV PATHOGENESIS

clinicaloptions.com/hiv

HIV Entry and Tropism

HIV Life Cycle

Maturation2. Membrane

fusion & entry

9. Budding

3. Uncoating & reverse

transcription

4. Nuclearuptake 5. Integration

6. Transcription & RNA processing

7. Nuclearexport 8. Translation

& Assembly1. Receptor

binding

Adherence receptor antagonists

Fusion inhibitors

Reverse transcriptase inhibitors

Integrase inhibitors

Protease inhibitors

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

HIV AND PSYCHIATRIC COMORBIDITIES

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

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

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

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

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

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

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.

Adapted from Ulett et al. 2009

Engagement in Care: More than just taking your meds

Diagnosis of HIV

Linkage to care

ART initiation

ART adherence Outcomes

Retention in Care

Re-engagement in care

Adapted from Gardner et al. 2011 and Health Resources and Services Administration (HRSA)

19%

20%

59%

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)

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)

Engagement at UVa

2009 2010 20110%

10%

20%

30%

40%

50%

60%

5.67%9.90% 10.09%

47.00%

51.00%56.00%

Undetectable VLOut of Care

Calendar Year

Perc

enta

ge o

f pati

ents

Factors associated with poor engagement

Adapted from Ulett et al. 2009

Diagnosis of HIV

Linkage to care

ART initiation

ART adherenc

e

Outcomes

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 (?)

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

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 behaviors3-5

• 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.

IPV and HIV1,2

• IPV Prevalence– HIV+ women ~ 14-67%– 23% - 53.1% of HIV+ men and women3

• Increased lifetime trauma associated with:– AIDS-related mortality – all-cause mortality in HIV+ patients– decreased adherence to ART4

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.

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

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

Characteristic Overall sample (n=251)

Age, years [n(%)] 18-45 129 (51.4) 46-82 122 (48.6)

Gender [n(%)] Male 187 (74.5)

Female 64 (25.5) Race [n(%)]

White 138 (55.0) African-American 99 (39.4)

Pacific/Other 10 (4.0) Native American 2 (0.8)

Unknown 1 (0.4) Declined to answer 1 (0.4)

Sexual orientation [n(%)] Men who have sex with men 131 (52.2)

Heterosexual men 50 (19.9) Heterosexual females 56 (22.3)

Women who have sex with women 7 (2.8) Declined to answer 7 (2.8)

Median CD4 count, cells/mm3 (range) 551 (3-1927) Undetectable Viral Load [n(%)] 117 (46.4) History of IPV [n(%)] 83 (33.1) Lifetime traumatic experiences [Median(IQR)] (n=246)

11.00 (8.00-14.25)

Schafer et al.AIDS Patient Care & STDs 2012.

IPV negative IPV positive0.0%

10.0%

20.0%

30.0%

40.0%

50.0%

60.0%

70.0%

80.0%

90.0%

100.0%

CD4>=200

CD4<200

Non-detectable VL

Detectable VL

*

**

*

**

*p=0.005**p=0.04n=13

n=8

n=46

n=70

IPV exposure predicts worse HIV outcomes

Schafer et al.AIDS Patient Care & STDs 2012.

Variable CD4<200 Detectable VL High NSR (> 33%)

RR(95% CI) P value RR (95% CI) p value RR (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

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

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

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 participantsDr. Norman Moore and the Department of Psychiatry at

Quillen College of Medicine

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.

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

Psychotropics Interact with ARVsOlanzapine Ritonavir shown to decrease

levels of olanzapine up to 50% in volunteers (J Clin Pharm 2002.)

Follow clinically, may need higher doses, (levels are available)

Risperdone In theory risperdone levels may be higher if on ritonavir

Start lower doses and follow clinically, look for EPS with ritonavir/indinavir.

Quetiapine May 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

Ziprasidone Levels may be increased with PIs, decreased with efavarenz

Start lower doses, monitor QTC (do so with all antipsychotics)

Aripiprazole Levels may be increased with PIs, decreased with efavarenz

Has akathisia as common side effect in this population

Clozapine Avoid with ritonavir due to levels increased/decreased

Haloperidol Levels may be increased with PIs, decreased with efavarenz

Lower starting levels with ritonavir co-administration

Slide courtesy of Gabrielle Marzani MD