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
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
HIV PATHOGENESIS
Image from Cornell Chronicle
HIV Entry and Tropism
HIV Life Cycle
Fusion
inhibitors
Adherence
receptor
antagonists
1. Receptor
binding
2. Membrane
fusion & entry
Reverse
transcriptase
inhibitors
3. Uncoating
& reverse
transcription
Protease
inhibitors
7. Nuclear
8. Translation
export
& Assembly
6. Transcription
& RNA processing
4. Nuclear
uptake
Integrase
inhibitors
Maturation
9. Budding
5. Integration
clinicaloptions.com/hiv
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)
Asymptomatic
neurocognitive
impairment
(ANI)
Mild
neurocognitive
disorder
(MND)
Severity
Mind Exchange Working Group; Clin Infect
Dis. (2012)
HIV-associated
dementia
(HAD)
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.
Engagement in Care: More than just
taking your meds
Re-engagement in
care
Retention in Care
Adapted from Ulett et al. 2009
20%
59%
19%
Adapted from Gardner et al. 2011 and Health Resources and Services Administration
(HRSA)
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 Universitybased 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
60%
Percentage of patients
51.00%
50%
56.00%
47.00%
40%
30%
Undetectable VL
Out of Care
20%
10%
9.90%
10.09%
2010
Calendar Year
2011
5.67%
0%
2009
Factors associated with poor
engagement Intimate partner violence (?)
•Younger age
•Higher baseline CD4
•Substance abuse
Re-engagement in
care
Retention in Care
•Older age
•African American race
•Higher baseline viral load
•Missed visits
•Higher baseline CD4
Adapted from Ulett et al. 2009
•Lifetime traumatic events
•Depression
•Poor coping
•Limited social support
•Stress
•Uninsured status
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.
2.
3.
Tjaden, et al. US DOJ 2000.
Houston E, et al. J Urban Health 2007;84:681-90.
Bonomi AE, et al. J Womens Health 2007;16:987-97.
4.
5.
Campbell JC. Lancet 2002; 359: 1331-6.
Breiding MJ, et al. Ann Epidemiol 2008;18:538-44.
IPV and HIV
1,2
• 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 • Socioeconomic status
Virginia and
– 54% at or below 100% of
Federal Poverty Level
neighboring states
– 31% uninsured
• Demographics
– 69% male
– 89% ages 25-64
– 43% Black/African
American
– 45% identify as menwho-have-sex-with-men
(MSM)
– 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
46-82
129 (51.4)
122 (48.6)
Male
Female
187 (74.5)
64 (25.5)
Gender [n(%)]
Race [n(%)]
White
African-American
Pacific/Other
Native American
Unknown
Declined to answer
Sexual orientation [n(%)]
Men who have sex with men
Heterosexual men
Heterosexual females
Women who have sex with women
Declined to answer
3
Median CD4 count, cells/mm (range)
Undetectable Viral Load [n(%)]
History of IPV [n(%)]
Lifetime traumatic experiences [Median(IQR)]
(n=246)
138
99
10
2
1
1
(55.0)
(39.4)
(4.0)
(0.8)
(0.4)
(0.4)
131 (52.2)
50 (19.9)
56 (22.3)
7 (2.8)
7 (2.8)
551 (3-1927)
117 (46.4)
83 (33.1)
11.00 (8.00-14.25)
Schafer et al.AIDS Patient Care & STDs 2012.
IPV exposure predicts worse HIV
outcomes
100.0%
CD4>=200
90.0%
80.0%
CD4<200
70.0%
Non-detectable VL
60.0%
Detectable VL
**
50.0%
n=46
**
40.0%
n=70
30.0%
20.0%
*
10.0%
n=13
0.0%
*
*p=0.005
**p=0.04
n=8
IPV negative
IPV positive
Schafer et al.AIDS Patient Care & STDs
2012.
Multivariate Analysis – IPV Model
Variable
IPV Exposure
CD4<200
Detectable VL
High NSR (> 33%)
RR(95% CI)
P value
RR (95% CI)
p value
RR (95% CI)
3.97 (1.5110.42)
0.005
1.92 (1.053.54)
0.035
NS
Age
NS
0.51 (0.300.88)
0.015
NS
Positive PTSD screen
NS
0.31 (0.150.67)
0.003
NS
Overall life stressor
score
NS
1.07 (1.001.14)
0.040
Severity of Alcohol Use
NS
19.40 (1.60234.95)
0.020
1.08 (1.011.16)
NS
p value
0.035
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
Study participants
Dr. Norman Moore and the Department of Psychiatry at
Quillen College of Medicine
•
•
•
•
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
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 ARVs
Olanzapine
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
Haloperidol
Avoid with ritonavir due to levels
increased/decreased
Levels may be increased with PIs,
decreased with efavarenz
Slide courtesy of Gabrielle Marzani MD
Lower starting levels with
ritonavir co-administration