HIV-Associated Neurocognitive Disorders: A Practical Approach

 
A Practical Approach to HIV-Associated
Neurocognitive Disorders
 
Drexel University College of Medicine
Division of Infectious Diseases and HIV Medicine
Grand Rounds
January 16, 2015
 
 
 
Mary Ann Adler Cohen, MD, FACP, FAPM, DLFAPA
Clinical Professor of Psychiatry
Icahn School of Medicine at Mount Sinai
Chair and Founder, Academy of Psychosomatic
Medicine HIV/AIDS Psychiatry Special Interest Group
Chair and Co-Founder of the World Psychiatric
Association Section on HIV/AIDS Psychiatry
Former Director, AIDS Psychiatry, Mount Sinai Medical
Center
Former Director, Consultation-Liaison Psychiatry Service
Metropolitan Hospital Center
 
Disclosure: Mary Ann Adler Cohen, MD
 
   
With respect to the following presentation,
there has been no relevant financial
relationship between the party listed above
(and/or spouse/partner) and any for-profit
company in the past 24 months which could
be considered a conflict of interest
 
Introduction
 
HIV/AIDS: severe, stigmatized, and complex
multimorbid medical and psychiatric illnesses
with a profound impact on patients, families,
and caregivers
HIV-Associated Neurocognitive Disorders
(HANDs) magnify HIV-associated
discrimination and stigma
Understanding HANDs can provide you with
the tools to prevent and treat HIV-associated
dementia
 
Outline of Presentation
 
Prevalence of HAND and its Impact on
Adherence to Risk Reduction, Medical Care,
and ART
Treatment as prevention of HAND
Definition and Classification of Cognitive
Disorders and HANDs
Controversial Aspects of HANDS: Diagnosis,
Screening and Treatment of HAND
Clinical Pearls for Treatment of HAND
 
 
 
Prevalence of HAND
 
The prevalence of HIV-associated dementia (HAD)
decreased following the development of effective
combination antiretroviral therapy (ART) in 1995
In persons with access and adherence to ART, HAD
prevalence is estimated to have decreased from 15%
(MacArthur et al. 1993) to less than 5% (Heaton et al.
2010)
However, there has been little change in the
prevalence of asymptomatic neurocognitve
impairment (ANI) and mild neurocognitive impairment
(MCI) (Tozzi et al. 2007, Simioni et al. 2010)
The prevalence of HAND in HIV is about 40 to 50%
The work of Heaton, Letendre, Tozzi, Simioni, Cysique,
Spudich, and others suggests that the CNS provides an
independent reservoir for HIV
 
Treatment as Prevention: CNS as
Independent Reservoir for HIV Replication
 
Starting ARVs as soon as the diagnosis of HIV is made
may prevent the development of an independent
reservoir for HIV replication in the CNS and thus
prevent future development of HAND and HAD
Pre-exposure prophylaxis (PrEP) and post-exposure
prophylaxis (PEP) can prevent HIV transmission and
also can prevent HAND
Treatment as prevention of HIV, HAND, and HAD
 
Heaton RK, Franklin DR, Ellis RJ, McCutchen JA, Letendre SL et al. HIV-associated
neurocognitive disorders before and during the era of combination antiretroviral
therapy: differences in rates, nature, and predictors. J Neurovirol. 2011; 17:3–16
Karim SSA et al. NEJM 2012;367:462
Jay SJ and Gostin LE. JAMA 2012 ;308:867
Marrazzo JM et al. JAMA 2014:312:390.
 
 
 
 
 
 
 
 
 
 
 
Prevalence of HAND in the ART Era
 
Current Estimate is about 40% to 50%
Cysique LA, Maruff P, Brew BJ. Prevalence and pattern of neuropsychological impairment in human immunodeficiency virus-
infected/acquired immunodeficiency syndrome (HIV/AIDS) patients across pre- and post-highly active antiretroviral therapy eras: a
combined study of two cohorts. J Neurovirol 2004; 10:350–357
Cysique L, Murray JM, Dunbar M, Jeyakumar V, Brew BJ. A screening algorithm for HIV-associated neurocognitive disorders. HIV
Medicine 2010;11:642-649.
Heaton R, Franklin D, Clifford D et al. Persistence and progression of HIV-associated neurocognitive impairment (NCI) in the era of
combination antiretroviral therapy (CART) and the role of comorbidities: the CHARTER study. 5th International AIDS Society
Conference on HIV Pathogenesis, Treatment and Prevention. Cape Town, South Africa. July, 2009. (Abst)
Heaton RK, Clifford D, Franklin DR, Woods SP et al. for the CHARTER Group. HIV-associated neurocognitive disorders persist in the era of
potent antiretroviral therapy: CHARTER Study. Neurology 2010; 75:2087–2096
Heaton RK, Franklin DR, Ellis RJ, McCutchen JA, Letendre SL et al. HIV-associated neurocognitive disorders before and during the era of
combination antiretroviral therapy: differences in rates, nature, and predictors. J Neurovirol. 2011; 17:3–16
Goodkin K, Cahn P, Concha M et al. Prevalence of HIV-1-associated Neurocognitive Disorders in Argentina. 5th International AIDS Society
Conference on HIV Pathogenesis, Treatment and Prevention. Cape Town, South Africa. July, 2009. (Abst)
Garvey L, Yerrakalva D, Winston A. High rates of asymptomatic neurocognitive impairment (aNCI) in HIV-1 infected subjects receiving
stable combination anti-retroviral therapy (CART) with undetectable plasma HIV RNA. 5th International AIDS Society Conference on
HIV Pathogenesis, Treatment and Prevention. Cape Town, South Africa. July, 2009. (Abst)
Vassallo M, Harvey-Langton A, Malandain G et al. The Neuradapt Study: Clinical, Radiological and Immunovirologic Findings in Patients
with HIV-associated Neurocognitive Disorders. 17th Conference on Retroviruses and Opportunistic Infections. San Francisco, United
States of America. February, 2010. (Abst)
Ciccarelli N, Fabbiani M, Di Giambenedetto S et al. Prevalence and Correlates of Minor Neurocognitive Disorders in Asymptomatic HIV-
infected Outpatients. 17th Conference on Retroviruses and Opportunistic Infections. San Francisco, United States of America.
February, 2010. (Abst)
Robertson KR, Smurzynski M, Parsons TD, Wu K, Bosch RJ, Wu J,McArthur JC, Collier AC, Evans SR, Ellis RJ. The prevalence and incidence
of neurocognitive impairment in the HAART era. AIDS 2007;  21:1915–1921
Royal W, Akomolafe A, Habib A et al. Neurocognitive Impairment and HIV in Nigeria: Functional and Virologic Correlates. 17th
Conference on Retroviruses and Opportunistic Infections. San Francisco, United States of America. February, 2010. (Abst)
Simioni S, Cavassini M, Annoni JM, Rimbault Abraham A, Bourquin I, Schiffer V, Calmy A, Chave JP, Giacobini E, Hirschel B, Du Pasquier RA
(2010) Cognitive dysfunction in HIV patients despite long-standing suppression of viremia. AIDS 24:1243– 1250
 
Prevalence of Neurocognitive
Impairment 
in Relation to
 ART Era
 
Definitions of Mild Cognitive
Syndromes, Dementia, and Delirium
 
Asymptomatic neurocognitive impairment (ANI): Mild to
moderate impairment in at least two cognitive domains but
without obvious impairment in daily functioning
Mild cognitive impairment (MCI): Mild to moderate
impairment in at least two cognitive domains that at least
mildly interferes with daily activities
Dementia: A clinical syndrome not entirely due to delirium
consisting of global cognitive decline with several areas being
affected and significant impact on daily functioning
Delirium: A clinical syndrome of global impairment of
cognition especially orientation and attention, including
abnormal sleep-wake cycle, thinking, perception, language
and affect with acute onset and fluctuating course
 
 
Delirium – Terms Used
 
Acute brain failure
Acute cerebral insufficiency
Acute confusional state
Encephalopathy
Intensive Care Unit (ICU) Psychosis
Reversible toxic psychosis
 
Delirium Subtypes
 
Hyperactive Delirium
Hypervigilance
Restlessness
Fast/loud speech
Anger/irritability
Combativeness 46%
Impatience
Uncooperative
Laughing
Swearing/singing 30%
Euphoria
Wandering
Easy startle
Distractibility
Nightmares
Persistent thoughts
Misdiagnosed as psychosis, mania
 
 
Meagher, 1996
 
Hypoactive Delirium
Unawareness
Lethargy
Decreased alertness
Staring
Sparse/slow speech
Apathy
Decreased motor activity
Often misdiagnosed as depression
 
Delirium can be
Hyperactive
Hypoactive
Mixed
Superimposed on dementia
 
 
 
 
Liptzin and Levkoff. Br J Psych 1999
 
 
 
 
 
Delirium vs. Dementia
 
Delirium
Acute or abrupt onset
Fluctuation of symptom severity
over 24-hour period
Reversible when cause is treated
Impaired level of consciousness
Impaired attention, orientation,
memory, executive functions
Illusions, hallucinations (visual)
Delusions – poorly formed,
fleeting and paranoid
Reversal of sleep-wake cycle,
insomnia
Affective lability
Irritability
Hypoactive – often misdiagnosed
as depression
Hyperactive – often misdiagnosed
as psychosis
 
Dementia
Insidious
Non-fluctuating
Progressive, 85% not reversible
Clear level of consciousness
unless delirium is superimposed
or the dementia is end-stage
Impaired memory
Can have visual or auditory
hallucinations
Delusions – paranoid and fixed
Apathy
Apraxia
Agnosia
Aphasia
Amnesia
 
 
 
 
Signs and Symptoms of
Normal Aging versus Dementia
 
    
Normal Aging and Cognition
New onset beginning at age 50
Lack of progression
Subjective memory complaints
Annoying but not disabling
Frequent problems with name
retrieval
Minor difficulties in recalling
detailed events
Problems related to
overloaded neuronal systems
Not associated with any other
signs or symptoms
May be intermittent
Prevalence is estimated at 18%
 
    
Alzheimer’s Dementia
Insidious onset
Unrelentingly progressive
impairment
Prominent memory
impairment
Leading cause of dementia
and functional disability in the
elderly
50 to 75% of all dementia is
Alzheimer’s
The 4 As of Alzheimer’s
Dementia:
     Amnesia, Aphasia, Apraxia,
Agnosia
Prevalence is 6.5%
 
 
 
Neuropsychological Profile
Normal Aging versus Dementia
 
   
Normal Aging
Loss of speed and efficiency
of information processing
Impaired fluid abilities –
novel problem-solving
Deficiencies in memory
retrieval
Modest declines in delayed
free recall
Decrements on executive
tests of visuoperceptual,
visuospatial, and
constructional functions
 
Alzheimer’s Dementia
Impaired memory
consolidation with rapid
forgetting
Diminished executive skills
Impaired semantic fluency
     and naming
Impaired visuospatial
analysis and praxis
Rapid forgetting of new
information after brief
delays
 
Cortical versus Subcortical
Dementia
 
  
Cortical Dementia – 4 As
Amnesia - not helped by
cues
Aphasia
Agnosia
Apraxia
Alexia
Affective disorders – not
frequent
Loss of initiative
Psychomotor retardation
Gait – normal until late
Extrapyramidal signs - late
Pathological reflexes –
grasp, snout, suck,
Babinski - late
 
 
 
 
Subcortical Dementia – 4 Ds
Dysmnesia - helped by cues
Dysexecutive – difficulty with
planning and decision-making
Delay – slow thinking and moving
Depletion – reduced complexity
of thought
Affective disorders – severe
Apathy and inertia
Absence of the 4 As
Slow diminution of cognitive
functions
Psychomotor retardation
Abnormal gait
Loss of initiative, vitality, physical
energy and emotional drive
Extrapyramidal signs
 
Neuropsychological Profile
Normal Aging versus Dementia
 
   
Normal Aging
Loss of speed and efficiency
of information processing
Impaired fluid abilities –
novel problem-solving
Deficiencies in memory
retrieval
Modest declines in delayed
free recall
Decrements on executive
tests of visuoperceptual,
visuospatial, and
constructional functions
 
Alzheimer’s Dementia
Impaired memory
consolidation with rapid
forgetting
Diminished executive skills
Impaired semantic fluency
     and naming
Impaired visuospatial
analysis and praxis
Rapid forgetting of new
information after brief
delays
 
Definition and Classification of HIV-Associated
Neurocognitive Disorders (HANDs)
 
Asymptomatic Neurocognitive Impairment – ANI
– mild to moderate impairment in at least 2
domains without obvious impairment in daily
functioning
Mild Neurocognitive Impairment – MCI – mild to
moderate impairment in at least 2 domains with
at least mild interference with daily functioning
HIV-Associated Dementia – HAD – a subcortical
and cortical dementia that is severe enough to
cause functional impairment and is characterized
by slowed information processing, deficits in
attention and memory, and impairments in
abstraction and fine motor skills
 
HIV-Associated Neurocognitive Profile
 
Fronto-subcortical pattern in the following domains:
 
 
Attention / Working Memory
 
Executive Functioning
 
Information Processing Speed
 
Verbal Fluency
 
Learning
 
Motor Function
 
Verbal Memory
 
Differentiating Delirium from
HIV- Associated Dementia
 
 
Clinical Pearls for Differential Diagnosis of Psychiatric
Symptoms in HIV and AIDS
 
There is a need for a comprehensive biopsychosocial approach
to psychiatric symptom evaluation in persons with HIV/AIDS
This comprehensive approach to differential diagnosis includes
exploring clues for infectious, neurologic, and psychiatric causes
and requires complete medical, psychiatric, and psychosocial
assessments as well as ancillary evaluations
Delirium is prevalent in inpatient medicine and may be
superimposed on HIV-associated dementia
  
Cohen, 1987, 1992; Cohen et al., 2010; Cohen and Alfonso, 2004; Cohen and Chao,2008;
   Cohen and Gorman, 2008; Cohen and Weisman, 1986, 1988;
   Peterson et al. J Am Geriatr Soc 2006; Pandharipande et al. IntensiveCare Med, 2007;
Khurana et al Geriatr Gerontol Int, 2011
 
Clinical Pearls for Prevention and
Recognition of HANDs
 
Each person with HIV needs a complete cognitive
assessment at baseline and on a semi-annual or
at least annual basis and whenever there is
evidence of a change in cognitive function
HIV-associated dementia can be prevented by
early diagnosis of HIV infection and initiation of
antiretroviral therapy immediately upon exposure
to or diagnosis of HIV
HAND can be prevented by pre-exposure (PrEP)
prophylaxis and post-exposure prophylaxis (PEP)
Cognitive impairment can contribute to
nonadherence at any age or stage of HIV infection
 
Clinical Pearls for Prevention and
Recognition of Cognitive Disorders
 
Antiretroviral therapy may prevent HAND,
prevent HAND progression, and, at times, reverse
cognitive impairment
HAND is still prevalent and is the most common
treatable cause of dementia in persons under 50
years of age (Ances and Ellis, 2007)
Hypoactive delirium is prevalent in persons with
HIV and AIDS, can masquerade as depression, can
be superimposed on HIV-associated dementia,
    and is easily resolved if or when the underlying
cause is identified and treated
 
 
 
 
Risk Factors for HAD
 
Older age
History of CNS disease
Shorter duration of antiretroviral treatment
Low CD4 (current and nadir)
Asymptomatic neurocognitive impairment (ANI)
Mild neurocognitive impairment (MCI)
Co-infection with hepatitis C (HCV)
Insulin resistance, cardiovascular illnesses, metabolic syndrome
Seroconversion disorder
Anemia
Vitamin deficiencies (B6, B12)
High CSF viral load
Depression
Alcohol, amphetamines, cocaine
 
 
Valcour V, Sacktor N, Paul R et al. 
Insulin resistance is associated with cognition among HIV-1-
infected patients: the Hawaii Aging with HIV cohort.
  J Acquir Immun Defic Syndr
2006;43:405-410.
Cysique L, Murray JM, Dunbar M, Jeyakumar V, Brew BJ. 
A screening algorithm for HIV-associated
neurocognitive disorders. HIV Medicine 2010;11:642-649.
 
 
Alzheimer’s Dementia (AD) versus
HIV-Associated Dementia (HAD) – Note Overlap
 
   AD
Age over 65 years
Insidious onset
Unrelentingly progressive
impairment
Prominent memory impairment
Amnesia
Aphasia
Apraxia
Agnosia
Impaired semantic fluency
      and naming
Impaired visuospatial analysis and
praxis
Rapid forgetting of new
information after brief delays
May have incontinence
May have cortical release signs
 
 
 
HAD
Can occur at any age over 18
Can be prevented
Can be reversed with antiretrovirals
Cognitive slowing
Psychomotor slowing
Impaired attention and
concentration
Impaired impulse control
Impaired executive function
Apathy
Regression
Psychosis
Mood disorders
Dropping things
Impaired balance
Ataxia, tremor
Incontinence can occur late
 
 
 
 
What is Your Diagnosis of Mr. A’s
Cognitive Impairment?
 
Mr. A is a 64 year old with AIDS diagnosed in 1997
when he was found to have late-stage AIDS and a
CD4 of 17 who self-referred in 2012 because of
memory impairment, difficulty retaining new
information, and multitasking
Fluent in Greek, Russian, Italian, Portuguese,
Spanish, French, and English, he resigned from his
job at an international firm because he himself
noticed that he was making mistakes
He mourns both the loss of his job and the loss of his
excellent memory that was once a source of great
pride
 
What is the Differential Diagnosis of
Mr. A’s Memory Impairment?
 
 
What is the Differential Diagnosis of
Mr. A’s Memory Impairment?
 
Delirium
Mood disorder with depressive features
Substance use disorder
Mr. A had no evidence of delirium, depression, or
substance use
MMSE is 30 and his clock and Bender drawings,
formal tests of recall, registration, Mental Alternation
Test (verbal Trailmaking), similarity testing, proverb
interpretation, and serial 7s are all within normal
limits
 
 
What is the Diagnosis of Mr. A’s
Memory Impairment?
 
His own complaints and validation by collateral
informants suggest that his diagnosis is probably
consistent with HIV-associated mild neurocognitive
impairment (MCI) however, since he performed well
on cognitive testing and did not have NP testing we
cannot make this diagnosis.
    There is  a need for a complete comprehensive
cognitive assessment of persons with HIV/AIDS,
    better criteria for diagnosis of HAND, and at times
for neuropsychological testing.
 
 
HIV/AIDS:
A Paradigm for Comprehensive and Compassionate
Care with a Biopsychosocial Approach
 
Complex and severe medical and psychiatric
illness
Persons with HIV/AIDS are vulnerable
Medically
Psychiatrically
Socially
 
Cohen MA and Gorman JM. 
Comprehensive Textbook of AIDS
Psychiatry
. Oxford University Press, New York, 2008
      
Cohen MA, Goforth HW, Lux JZ, Batista SM, Khalife S, Cozza
         KL, and Soffer J. 
Handbook of AIDS Psychiatry
. Oxford
         University Press, New York, 2010.
 
 
 
 
Adherence to Prevention and Treatment
Adherence to Prevention and Treatment
 
Vulnerable Populations
Vulnerable Populations
 
Women
 
African-
American
 
Latino-
American
 
Men who
have sex
with men
 
Children
 
Addicted
 
Taboo
Taboo
Topics
Topics
 
Prevention
Prevention
 
Barrier contraception
Drug treatment
Safe sex
Sterile works
Trauma prevention
 
Sex
Trauma
Drugs
Infection
Death
 
 
 
Lethalit
Lethalit
y
y
 
 
Stigmatized Illness
Hepatitis C  STDs  TB
PTSD    Dementia    Delirium
Psychosis   Injecting Drug Use
 
Severe Multisystem
Severe Multisystem
Illness
Illness
 
 
 
Cardiac
Dermatological
Endocrinological
GI
Infectious
Neurological
Oncological
Ophthalmologic
Psychiatric
Pulmonary
Renal
 
 Elderly
 
 
 
Need for Recognition and Treatment
of Psychiatric Disorders
 
  
Vectors of HIV
  Barriers to adherence
  Psychiatric treatment:
      
  transmission
, morbidity, mortality, suffering
      
  adherence
 
Adherence
 
Need 95% adherence to ARVs
Need 100% adherence to safer sex
Need 100% adherence to use of sterile works
In the USA, only 29% of persons with HIV and
on ARVs have achieved viral suppression
Only 69% are linked to care and 59% are
retained in care
Thompson MA 
et al. 
Guidelines for improving entry into and retention in care
and antiretroviral adherence for persons with HIV: evidence-based
recommendations from an international association of physicians in AIDS
care panel. 
Ann Intern Med 
2012; 156:817-833
 
 
 
Adherence to Appointments and
Mortality in Persons with HIV
 
Mugavero and colleagues found that
adherence to HIV clinic appointments is
an independent predictor of all-cause
mortality in persons with HIV
 
Mugavero MJ et al. Beyond Core Indicators of Retention in HIV
Care: Missed Clinic Visits are Independently Associated with
All‐cause Mortality. 
Clinical Infectious Diseases 
2014; 59:1471-
1479
 
Tragic Results of Psychiatric Barriers to
Adherence
 
Lack of access to care
Nonadherence to care
Stopping and starting ARVs
Emergence of  viral mutations and viral
multidrug resistance
Development of independent CNS reservoirs
Dying of AIDS and other causes of mortality in
persons with HIV
 
Mr. B is a 37 year old disabled former investment
banker with AIDS (CD4 112 and elevated viral load)
who was admitted to a nursing home when he was
no longer able to care for himself in the community
or perform activities of daily living (ADLs) or
instrumental ADLs (IADLs). He was referred for
refusal to stay in the nursing home.
Mr. B’s history revealed that he was no longer able
to care for his partner or himself, wandered away
from their apartment and got lost, and did not
believe that he was ill or that he had AIDS.
 
 
 
 
 
 
 
 
 
 
 
What Psychiatric Disorder is a Factor
in Mr. B’s Refusal to Remain in a
Nursing Home?
 
On initial psychiatric consultation Mr. B denied being
ill or needing care. He wanted to return home to live
with his partner.
What is your diagnosis?
 
 
 
 
 
 
 
 
 
 
 
Diagnosis and Treatment of Mr. B
 
On initial psychiatric consultation Mr. B denied being
ill or needing care. He wanted to return home to live
with his partner.
He had impairment of memory, abstract thinking,
planning, and executive function.
Mr. B had anosognosia, constructional apraxia on
clock and Bender drawings, psychomotor
retardation, and profoundly diminished intellectual
functioning relative to his educational (MBA) and
occupational levels. He was incontinent of urine and
feces.
 
 
 
 
 
 
 
 
 
 
 
Diagnosis and Treatment of Mr. B
 
Mr. B met criteria for HIV-associated dementia (HAD).
After two years of directly administered ART in the
nursing home setting, evidence of HAD could not be
detected on psychiatric examination. Mr. B was able
to resume independent living and went from
disabled young man in diapers to dapper investment
banker.
     Dementia can occur at any age in persons with HIV
infection. Early treatment with ART and early
recognition of HAND can lead to decrease or
resolution of cognitive impairment and restoration of
function in some persons with HIV/AIDS.
 
 
 
 
 
 
 
 
 
 
 
 
 
Diagnosis and Treatment of Mr. B
 
This vignette illustrates that although ART has had a major
impact on both morbidity and mortality in persons with AIDS,
HAND is still prevalent and is the most common treatable
cause of dementia in persons under 50 (Ances and Ellis, 2007)
It is important to diagnose HIV infection early and begin ART,
since there is evidence that HIV has an affinity for neural
tissue and can establish independent reservoirs in the brain
Every person with HIV infection needs a comprehensive
evaluation for cognitive impairment at baseline and at least
twice yearly to ensure early diagnosis and of HAND
Comprehensive psychiatric assessment for HAND and other
psychiatric disorders in persons with HIV and AIDS is described
in the 
Handbook of AIDS Psychiatry
HAND is a prevalent diagnosis young persons as well as in
elderly persons with HIV/AIDS
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Diagnosis and Treatment of
HAND
 
HAND is found in 69% of virally suppressed persons with
HIV (Simioni et al. 2010)
Current estimates of HAND prevalence is 40% - 50%
(CHARTER 2014)
Neurocognitive disorders can resemble depression and
are seldom diagnosed
Diagnosis requires complete cognitive assessment but
brief screening can help lead to diagnosis
HAD leads to nonadherence with HIV care
HAD may reverse with ART
Once treated, adherence improves, preventing illness
progression
 
 
 
 
 
 
 
 
 
 
 
 
HIV-Associcated Neurocognitive
Disorder (HAND)
 
The “gold standard” is a full battery of neuropsychological
testing administered by a neuropsychologist
Unavailable in most clinical settings
Often available only as part of a research study
Unavailable in resource-limited settings
Efforts are made to develop reliable and valid screening
tools but no screening tool has been identified thus far
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Screening for HIV-Associated
Neurocognitive Disorders (HAND)
 
Do you experience frequent memory loss - do you forget the
occurrence of special events even the more recent ones?
  Do you feel that you are slower when reasoning, planning
       activities, or solving problems?
  Do you find it more difficult to perform activities that used to be
       automatic for you (paying bills, writing checks, making plans)
  Do you have difficulties paying attention (to a conversation, a
       book, or a movie)?
  Do you have difficulty with complex learned tasks that were
       previously  easy for you (playing the piano, speaking a second
       language, knitting a sweater)?
 
Simioni et al, AIDS 2010 - adapted with additions
 
 
 
 
 
 
 
 
 
 
HIV-Associated Neurocognitive Disorders:
Screening with Simioni Questions
 
The HIV Dementia Scale (HDS) was developed to screen
for HAD
The International HIV Dementia Scale (IHDS) was
developed for global use
The Montreal Cognitive Assessment (MoCA) was
developed to screen for HAND but reliability and validity
are not adequate
 
Power C, Selnes OA, Grim JA, McArthur JC. HIV Dementia Scale: a rapid screening test. 
J Acquir Immune
Defic Syndr Hum Retrovirol
 1995; 8:273–278
Sacktor NC, Wong M, Nakasujja N, Skolasky RL, Selnes OA, Musisi S, et al. The International HIV
Dementia Scale: a new rapid screening test for HIV dementia. 
AIDS
 2005; 19:1367–1374
Koski L, Brouillette MJ, Lalonde R, Hello B, Wong E, Tsuchida A, et al. Computerized testing augments
pencil-and-paper tasks in measuring HIV-associated mild cognitive impairment. 
HIV Med
 2011; 12:472–
480
 
 
 
 
 
 
 
 
 
 
 
 
 
 
HIV-Associated Neurocognitive Disorders:
The Use of Screening Tools is Controversial
 
Zipursky AR et al. Evaluation of brief screening
tools for neurocognitive impairment in
HIV/AIDS: a systematic review of the
literature.
 AIDS
 2013; 27:2385–2401.
 
There is no adequate, reliable, valid screening
tool for the diagnosis of HAND
 
 
 
 
 
 
 
 
 
 
HIV-Associated Neurocognitive Disorders:
The Use of Screening Tools is Controversial
 
Controversy in Diagnosis of HAND
 
No reliable and valid screening instrument has
been developed as yet
The best approach is neuropsychological
testing – can be abbreviated and utilized
Do not use the Mini Mental State Examination
Can use the Simioni questions and clock
drawing for a baseline and semiannual
assessment
 
Controversy in Treatment of HAND:
How Important is CPE Rank?
 
Initially thought to be important, the ability of
ART to cross the blood brain barrier, or the
CNS penetration effectiveness (CPE) rank is
now in question
Is lowering CNS viral load correlated with
clinical improvement?
Letendre S et al. Arch Neurol 2008;65:65
Caniglia EC et al. Neurology 2014
Ellis RJ et al. CID 2014;58:1015.
 
 
 
Crisis Intervention
 Individual psychodynamic psychotherapy
 Supportive psychotherapy
 Cognitive behavioral therapy
 Group psychotherapy
 Couple therapy
 Family therapy
 Bereavement therapy
 Substance use treatment
 Palliative psychiatry
 Psychoeducational approaches to prevention
 Psychopharmacology
 
 
 
 
 
 
 
 
 
 
 
 
Treatment of Psychiatric
Disorders in Persons with HAND
 
 
Provide a safe environment to discuss concerns about HIV,
its stigma, and its treatments
Provide support from both members and leaders
Confidential
Non-judgmental
Compassionate
Caring
“All in the same boat”
Acceptance and sense of family
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Treatment of Psychiatric Disorders in
Persons with HAND: Support Groups
 
 
 
Exercise emphasizing walking, balance, core strength
 Relaxation response
 Yoga, Qigong, Tai Chi
 Music therapy, dance therapy
 Reading, crossword and jigsaw puzzles, Ken Ken, movies
 Brain games including computer use
 Education and involvement of family in care
 Spiritual assessment and support
 Development of support networks if family or friends are
     unavailable
 Directly observed ART and other medications where
     indicated
 
 
 
 
 
 
 
 
 
 
 
 
Integrative Treatments for Persons
with HAND: Alleviation of Symptoms
 
 
 
High prevalence of multimorbid psychiatric disorders
 Increased risk of suicide
 Vulnerability to all side effects of medications
 Increased vulnerability to the psychiatric side effects of
     antiretroviral medications
 Increased vulnerability to anticholinergic side effects of
     medications (includes antihistamines, antispasmodics,
     most psychotropic medications, some ARVs, and warfarin)
 Special affinity of HIV to basal ganglia makes for high risk
     for extrapyramidal side effects especially psychotropic
     medications and antiemetics (except ondansetron)
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Psychopharmacologic Treatment of
Psychiatric Disorders in Persons with
HAND
 
START VERY LOW AND GO VERY SLOW
The maxim for geriatric psychiatry is even more
significant for AIDS psychiatry because of the
increased vulnerability of this population
In the US, 26% of persons with HIV and AIDS are over
50 years old
Avoid use of psychotropic medications except where
essential for safety or alleviation of distress
Avoid combinations of psychotropic medications if
possible to prevent multiplication of side effects
 
 
 
 
 
 
 
 
 
 
 
Use of Psychotropic Medications
in Persons with HAND
 
HIV/AIDS Psychopharmacology:
Effects on Patients
 
Slowing of Metabolism
Drug-Drug Interactions
Drug–Illness Interactions
vulnerability to dysglycemia
vulnerability to anticholinergic side effects
vulnerability to extrapyramidal side effects
vulnerability to falls
vulnerability to confusion
vulnerability to lipodystrophy
 
 
 
 
 
 
The Role of Collaborative Care in the
HIV Pandemic
 
Prevention
 
Can promote adherence to:
safe sex
drug treatment
harm reduction
needle exchange
 
Treatment
 
Can improve adherence to:
medical care
antiretrovirals
 
Can decrease:
suffering
morbidity
mortality
 
Academy of Psychosomatic Medicine
HIV/AIDS Psychiatry Special Interest Group
and World Psychiatric Association Section on HIV/AIDS Psychiatry
 
Founded 2003, meets annually at the APM
To develop networks
To present work and share findings
To develop consensus on treatment
To develop collaborative research
To educate other clinicians and trainees
Has 337 mental health clinician members
We welcome new members
Presentations at WPA meetings throughout the world
macohen@nyc.rr.com
 to join – no dues
www.apm.org/sigs/oap
 
 
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HIV/AIDS presents complex medical and psychiatric challenges, including HIV-Associated Neurocognitive Disorders (HANDs), which impact patients, families, and caregivers. This presentation by Dr. Mary Ann Adler Cohen provides insights into the prevalence, impact, diagnosis, and treatment of HANDs, emphasizing the importance of preventing and managing HIV-associated dementia. With a focus on adherence to treatment and risk reduction, understanding HANDs is crucial in holistic HIV care.

  • HIV
  • Neurocognitive Disorders
  • HIV/AIDS Psychiatry
  • Medical Care

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  1. A Practical Approach to HIV-Associated Neurocognitive Disorders Drexel University College of Medicine Division of Infectious Diseases and HIV Medicine Grand Rounds January 16, 2015

  2. Mary Ann Adler Cohen, MD, FACP, FAPM, DLFAPA Clinical Professor of Psychiatry Icahn School of Medicine at Mount Sinai Chair and Founder, Academy of Psychosomatic Medicine HIV/AIDS Psychiatry Special Interest Group Chair and Co-Founder of the World Psychiatric Association Section on HIV/AIDS Psychiatry Former Director, AIDS Psychiatry, Mount Sinai Medical Center Former Director, Consultation-Liaison Psychiatry Service Metropolitan Hospital Center

  3. Disclosure: Mary Ann Adler Cohen, MD With respect to the following presentation, there has been no relevant financial relationship between the party listed above (and/or spouse/partner) and any for-profit company in the past 24 months which could be considered a conflict of interest

  4. Introduction HIV/AIDS: severe, stigmatized, and complex multimorbid medical and psychiatric illnesses with a profound impact on patients, families, and caregivers HIV-Associated Neurocognitive Disorders (HANDs) magnify HIV-associated discrimination and stigma Understanding HANDs can provide you with the tools to prevent and treat HIV-associated dementia

  5. Outline of Presentation Prevalence of HAND and its Impact on Adherence to Risk Reduction, Medical Care, and ART Treatment as prevention of HAND Definition and Classification of Cognitive Disorders and HANDs Controversial Aspects of HANDS: Diagnosis, Screening and Treatment of HAND Clinical Pearls for Treatment of HAND

  6. Prevalence of HAND The prevalence of HIV-associated dementia (HAD) decreased following the development of effective combination antiretroviral therapy (ART) in 1995 In persons with access and adherence to ART, HAD prevalence is estimated to have decreased from 15% (MacArthur et al. 1993) to less than 5% (Heaton et al. 2010) However, there has been little change in the prevalence of asymptomatic neurocognitve impairment (ANI) and mild neurocognitive impairment (MCI) (Tozzi et al. 2007, Simioni et al. 2010) The prevalence of HAND in HIV is about 40 to 50% The work of Heaton, Letendre, Tozzi, Simioni, Cysique, Spudich, and others suggests that the CNS provides an independent reservoir for HIV

  7. Treatment as Prevention: CNS as Independent Reservoir for HIV Replication Starting ARVs as soon as the diagnosis of HIV is made may prevent the development of an independent reservoir for HIV replication in the CNS and thus prevent future development of HAND and HAD Pre-exposure prophylaxis (PrEP) and post-exposure prophylaxis (PEP) can prevent HIV transmission and also can prevent HAND Treatment as prevention of HIV, HAND, and HAD Heaton RK, Franklin DR, Ellis RJ, McCutchen JA, Letendre SL et al. HIV-associated neurocognitive disorders before and during the era of combination antiretroviral therapy: differences in rates, nature, and predictors. J Neurovirol. 2011; 17:3 16 Karim SSA et al. NEJM 2012;367:462 Jay SJ and Gostin LE. JAMA 2012 ;308:867 Marrazzo JM et al. JAMA 2014:312:390.

  8. Prevalence of HAND in the ART Era Cysique LA, MaruffP, Brew BJ. Prevalence and pattern of neuropsychological impairment in human immunodeficiency virus- infected/acquired immunodeficiency syndrome (HIV/AIDS) patients across pre- and post-highly active antiretroviral therapy eras: a combined study of two cohorts. J Neurovirol 2004; 10:350 357 Cysique L, Murray JM, Dunbar M, Jeyakumar V, Brew BJ. A screening algorithm for HIV-associated neurocognitive disorders. HIV Medicine 2010;11:642-649. Heaton R, Franklin D, Clifford D et al. Persistence and progression of HIV-associated neurocognitive impairment (NCI) in the era of combination antiretroviral therapy (CART) and the role of comorbidities: the CHARTER study. 5th International AIDS Society Conference on HIV Pathogenesis, Treatment and Prevention. Cape Town, South Africa. July, 2009. (Abst) Heaton RK, Clifford D, Franklin DR, Woods SP et al. for the CHARTER Group. HIV-associated neurocognitive disorders persist in the era of potent antiretroviral therapy: CHARTER Study. Neurology 2010; 75:2087 2096 Heaton RK, Franklin DR, Ellis RJ, McCutchen JA, Letendre SL et al. HIV-associated neurocognitive disorders before and during the era of combination antiretroviral therapy: differences in rates, nature, and predictors. J Neurovirol. 2011; 17:3 16 Goodkin K, Cahn P, Concha M et al. Prevalence of HIV-1-associated Neurocognitive Disorders in Argentina. 5th International AIDS Society Conference on HIV Pathogenesis, Treatment and Prevention. Cape Town, South Africa. July, 2009. (Abst) Garvey L, Yerrakalva D, Winston A. High rates of asymptomatic neurocognitive impairment (aNCI) in HIV-1 infected subjects receiving stable combination anti-retroviral therapy (CART) with undetectable plasma HIV RNA. 5th International AIDS Society Conference on HIV Pathogenesis, Treatment and Prevention. Cape Town, South Africa. July, 2009. (Abst) Vassallo M, Harvey-Langton A, Malandain G et al. The NeuradaptStudy: Clinical, Radiological and Immunovirologic Findings in Patients with HIV-associated Neurocognitive Disorders. 17th Conference on Retroviruses and Opportunistic Infections. San Francisco, United States of America. February, 2010. (Abst) Ciccarelli N, Fabbiani M, Di Giambenedetto S et al. Prevalence and Correlates of Minor Neurocognitive Disorders in Asymptomatic HIV- infected Outpatients. 17th Conference on Retroviruses and Opportunistic Infections. San Francisco, United States of America. February, 2010. (Abst) Robertson KR, Smurzynski M, Parsons TD, Wu K, Bosch RJ, Wu J,McArthur JC, Collier AC, Evans SR, Ellis RJ. The prevalence and incidence of neurocognitive impairment in the HAART era. AIDS 2007; 21:1915 1921 Royal W, Akomolafe A, Habib A et al. Neurocognitive Impairment and HIV in Nigeria: Functional and Virologic Correlates. 17th Conference on Retroviruses and Opportunistic Infections. San Francisco, United States of America. February, 2010. (Abst) Simioni S, Cavassini M, Annoni JM, Rimbault Abraham A, BourquinI, SchifferV, Calmy A, Chave JP, Giacobini E, Hirschel B, Du Pasquier RA (2010) Cognitive dysfunction in HIV patients despite long-standing suppression of viremia. AIDS 24:1243 1250 Current Estimate is about 40% to 50%

  9. Prevalence of Neurocognitive Impairment in Relation to ART Era

  10. Definitions of Mild Cognitive Syndromes, Dementia, and Delirium Asymptomatic neurocognitive impairment (ANI): Mild to moderate impairment in at least two cognitive domains but without obvious impairment in daily functioning Mild cognitive impairment (MCI): Mild to moderate impairment in at least two cognitive domains that at least mildly interferes with daily activities Dementia: A clinical syndrome not entirely due to delirium consisting of global cognitive decline with several areas being affected and significant impact on daily functioning Delirium: A clinical syndrome of global impairment of cognition especially orientation and attention, including abnormal sleep-wake cycle, thinking, perception, language and affect with acute onset and fluctuating course

  11. Delirium Terms Used Acute brain failure Acute cerebral insufficiency Acute confusional state Encephalopathy Intensive Care Unit (ICU) Psychosis Reversible toxic psychosis

  12. Delirium Subtypes Hyperactive Delirium Hypervigilance Restlessness Fast/loud speech Anger/irritability Combativeness 46% Impatience Uncooperative Laughing Swearing/singing 30% Euphoria Wandering Easy startle Distractibility Nightmares Persistent thoughts Misdiagnosed as psychosis, mania Hypoactive Delirium Unawareness Lethargy Decreased alertness Staring Sparse/slow speech Apathy Decreased motor activity Often misdiagnosed as depression Delirium can be Hyperactive Hypoactive Mixed Superimposed on dementia Meagher, 1996 Liptzin and Levkoff. Br J Psych 1999

  13. Delirium vs. Dementia Delirium Acute or abrupt onset Fluctuation of symptom severity over 24-hour period Reversible when cause is treated Impaired level of consciousness Impaired attention, orientation, memory, executive functions Illusions, hallucinations (visual) Delusions poorly formed, fleeting and paranoid Reversal of sleep-wake cycle, insomnia Affective lability Irritability Hypoactive often misdiagnosed as depression Hyperactive often misdiagnosed as psychosis Dementia Insidious Non-fluctuating Progressive, 85% not reversible Clear level of consciousness unless delirium is superimposed or the dementia is end-stage Impaired memory Can have visual or auditory hallucinations Delusions paranoid and fixed Apathy Apraxia Agnosia Aphasia Amnesia

  14. Signs and Symptoms of Normal Aging versus Dementia Normal Aging and Cognition New onset beginning at age 50 Lack of progression Subjective memory complaints Annoying but not disabling Frequent problems with name retrieval Minor difficulties in recalling detailed events Problems related to overloaded neuronal systems Not associated with any other signs or symptoms May be intermittent Prevalence is estimated at 18% Alzheimer s Dementia Insidious onset Unrelentingly progressive impairment Prominent memory impairment Leading cause of dementia and functional disability in the elderly 50 to 75% of all dementia is Alzheimer s The 4 As of Alzheimer s Dementia: Amnesia, Aphasia, Apraxia, Agnosia Prevalence is 6.5%

  15. Neuropsychological Profile Normal Aging versus Dementia Normal Aging Loss of speed and efficiency of information processing Impaired fluid abilities novel problem-solving Deficiencies in memory retrieval Modest declines in delayed free recall Decrements on executive tests of visuoperceptual, visuospatial, and constructional functions Alzheimer s Dementia Impaired memory consolidation with rapid forgetting Diminished executive skills Impaired semantic fluency and naming Impaired visuospatial analysis and praxis Rapid forgetting of new information after brief delays

  16. Cortical versus Subcortical Dementia Subcortical Dementia 4 Ds Dysmnesia - helped by cues Dysexecutive difficulty with planning and decision-making Delay slow thinking and moving Depletion reduced complexity of thought Affective disorders severe Apathy and inertia Absence of the 4 As Slow diminution of cognitive functions Psychomotor retardation Abnormal gait Loss of initiative, vitality, physical energy and emotional drive Extrapyramidal signs Cortical Dementia 4 As Amnesia - not helped by cues Aphasia Agnosia Apraxia Alexia Affective disorders not frequent Loss of initiative Psychomotor retardation Gait normal until late Extrapyramidal signs - late Pathological reflexes grasp, snout, suck, Babinski - late

  17. Neuropsychological Profile Normal Aging versus Dementia Normal Aging Loss of speed and efficiency of information processing Impaired fluid abilities novel problem-solving Deficiencies in memory retrieval Modest declines in delayed free recall Decrements on executive tests of visuoperceptual, visuospatial, and constructional functions Alzheimer s Dementia Impaired memory consolidation with rapid forgetting Diminished executive skills Impaired semantic fluency and naming Impaired visuospatial analysis and praxis Rapid forgetting of new information after brief delays

  18. Definition and Classification of HIV-Associated Neurocognitive Disorders (HANDs) Asymptomatic Neurocognitive Impairment ANI mild to moderate impairment in at least 2 domains without obvious impairment in daily functioning Mild Neurocognitive Impairment MCI mild to moderate impairment in at least 2 domains with at least mild interference with daily functioning HIV-Associated Dementia HAD a subcortical and cortical dementia that is severe enough to cause functional impairment and is characterized by slowed information processing, deficits in attention and memory, and impairments in abstraction and fine motor skills

  19. HIV-Associated Neurocognitive Profile Fronto-subcortical pattern in the following domains: Attention / Working Memory Executive Functioning Information Processing Speed Verbal Fluency Learning Motor Function Verbal Memory

  20. Differentiating Delirium from HIV- Associated Dementia

  21. Clinical Pearls for Differential Diagnosis of Psychiatric Symptoms in HIV and AIDS There is a need for a comprehensive biopsychosocial approach to psychiatric symptom evaluation in persons with HIV/AIDS This comprehensive approach to differential diagnosis includes exploring clues for infectious, neurologic, and psychiatric causes and requires complete medical, psychiatric, and psychosocial assessments as well as ancillary evaluations Delirium is prevalent in inpatient medicine and may be superimposed on HIV-associated dementia Cohen, 1987, 1992; Cohen et al., 2010; Cohen and Alfonso, 2004; Cohen and Chao,2008; Cohen and Gorman, 2008; Cohen and Weisman, 1986, 1988; Peterson et al. J Am Geriatr Soc 2006; Pandharipande et al. IntensiveCare Med, 2007; Khurana et al Geriatr Gerontol Int, 2011

  22. Clinical Pearls for Prevention and Recognition of HANDs Each person with HIV needs a complete cognitive assessment at baseline and on a semi-annual or at least annual basis and whenever there is evidence of a change in cognitive function HIV-associated dementia can be prevented by early diagnosis of HIV infection and initiation of antiretroviral therapy immediately upon exposure to or diagnosis of HIV HAND can be prevented by pre-exposure (PrEP) prophylaxis and post-exposure prophylaxis (PEP) Cognitive impairment can contribute to nonadherence at any age or stage of HIV infection

  23. Clinical Pearls for Prevention and Recognition of Cognitive Disorders Antiretroviral therapy may prevent HAND, prevent HAND progression, and, at times, reverse cognitive impairment HAND is still prevalent and is the most common treatable cause of dementia in persons under 50 years of age (Ances and Ellis, 2007) Hypoactive delirium is prevalent in persons with HIV and AIDS, can masquerade as depression, can be superimposed on HIV-associated dementia, and is easily resolved if or when the underlying cause is identified and treated

  24. Risk Factors for HAD Older age History of CNS disease Shorter duration of antiretroviral treatment Low CD4 (current and nadir) Asymptomatic neurocognitive impairment (ANI) Mild neurocognitive impairment (MCI) Co-infection with hepatitis C (HCV) Insulin resistance, cardiovascular illnesses, metabolic syndrome Seroconversion disorder Anemia Vitamin deficiencies (B6, B12) High CSF viral load Depression Alcohol, amphetamines, cocaine Valcour V, Sacktor N, Paul R et al. Insulin resistance is associated with cognition among HIV-1- infected patients: the Hawaii Aging with HIV cohort. J Acquir Immun Defic Syndr 2006;43:405-410. Cysique L, Murray JM, Dunbar M, Jeyakumar V, Brew BJ. A screening algorithm for HIV-associated neurocognitive disorders. HIV Medicine 2010;11:642-649.

  25. Alzheimers Dementia (AD) versus HIV-Associated Dementia (HAD) Note Overlap AD Age over 65 years Insidious onset Unrelentingly progressive impairment Prominent memory impairment Amnesia Aphasia Apraxia Agnosia Impaired semantic fluency and naming Impaired visuospatial analysis and praxis Rapid forgetting of new information after brief delays May have incontinence May have cortical release signs HAD Can occur at any age over 18 Can be prevented Can be reversed with antiretrovirals Cognitive slowing Psychomotor slowing Impaired attention and concentration Impaired impulse control Impaired executive function Apathy Regression Psychosis Mood disorders Dropping things Impaired balance Ataxia, tremor Incontinence can occur late

  26. What is Your Diagnosis of Mr. As Cognitive Impairment? Mr. A is a 64 year old with AIDS diagnosed in 1997 when he was found to have late-stage AIDS and a CD4 of 17 who self-referred in 2012 because of memory impairment, difficulty retaining new information, and multitasking Fluent in Greek, Russian, Italian, Portuguese, Spanish, French, and English, he resigned from his job at an international firm because he himself noticed that he was making mistakes He mourns both the loss of his job and the loss of his excellent memory that was once a source of great pride

  27. What is the Differential Diagnosis of Mr. A s Memory Impairment?

  28. What is the Differential Diagnosis of Mr. A s Memory Impairment? Delirium Mood disorder with depressive features Substance use disorder Mr. A had no evidence of delirium, depression, or substance use MMSE is 30 and his clock and Bender drawings, formal tests of recall, registration, Mental Alternation Test (verbal Trailmaking), similarity testing, proverb interpretation, and serial 7s are all within normal limits

  29. What is the Diagnosis of Mr. As Memory Impairment? His own complaints and validation by collateral informants suggest that his diagnosis is probably consistent with HIV-associated mild neurocognitive impairment (MCI) however, since he performed well on cognitive testing and did not have NP testing we cannot make this diagnosis. There is a need for a complete comprehensive cognitive assessment of persons with HIV/AIDS, better criteria for diagnosis of HAND, and at times for neuropsychological testing.

  30. HIV/AIDS: A Paradigm for Comprehensive and Compassionate Care with a Biopsychosocial Approach Complex and severe medical and psychiatric illness Persons with HIV/AIDS are vulnerable Medically Psychiatrically Socially Cohen MA and Gorman JM. Comprehensive Textbook of AIDS Psychiatry. Oxford University Press, New York, 2008 Cohen MA, Goforth HW, Lux JZ, Batista SM, Khalife S, Cozza KL, and Soffer J. Handbook of AIDS Psychiatry. Oxford University Press, New York, 2010.

  31. Severe Multisystem Illness Cardiac Dermatological Endocrinological GI Infectious Neurological Oncological Ophthalmologic Psychiatric Pulmonary Renal Taboo Topics Sex Trauma Drugs Infection Death Stigmatized Illness Hepatitis C STDs TB PTSD Dementia Delirium Psychosis Injecting Drug Use HIV/AIDS Psychiatry Prevention Barrier contraception Drug treatment Safe sex Sterile works Trauma prevention Lethalit y Adherence to Prevention and Treatment Men who have sex with men African- American Latino- American Addicted Children Elderly Women Vulnerable Populations

  32. Need for Recognition and Treatment of Psychiatric Disorders Vectors of HIV Barriers to adherence Psychiatric treatment: transmission, morbidity, mortality, suffering adherence

  33. Adherence Need 95% adherence to ARVs Need 100% adherence to safer sex Need 100% adherence to use of sterile works In the USA, only 29% of persons with HIV and on ARVs have achieved viral suppression Only 69% are linked to care and 59% are retained in care Thompson MA et al. Guidelines for improving entry into and retention in care and antiretroviral adherence for persons with HIV: evidence-based recommendations from an international association of physicians in AIDS care panel. Ann Intern Med 2012; 156:817-833

  34. Adherence to Appointments and Mortality in Persons with HIV Mugavero and colleagues found that adherence to HIV clinic appointments is an independent predictor of all-cause mortality in persons with HIV Mugavero MJ et al. Beyond Core Indicators of Retention in HIV Care: Missed Clinic Visits are Independently Associated with All cause Mortality. Clinical Infectious Diseases 2014; 59:1471- 1479

  35. Tragic Results of Psychiatric Barriers to Adherence Lack of access to care Nonadherence to care Stopping and starting ARVs Emergence of viral mutations and viral multidrug resistance Development of independent CNS reservoirs Dying of AIDS and other causes of mortality in persons with HIV

  36. What Psychiatric Disorder is a Factor in Mr. B s Refusal to Remain in a Nursing Home? Mr. B is a 37 year old disabled former investment banker with AIDS (CD4 112 and elevated viral load) who was admitted to a nursing home when he was no longer able to care for himself in the community or perform activities of daily living (ADLs) or instrumental ADLs (IADLs). He was referred for refusal to stay in the nursing home. Mr. B s history revealed that he was no longer able to care for his partner or himself, wandered away from their apartment and got lost, and did not believe that he was ill or that he had AIDS.

  37. Diagnosis and Treatment of Mr. B On initial psychiatric consultation Mr. B denied being ill or needing care. He wanted to return home to live with his partner. What is your diagnosis?

  38. Diagnosis and Treatment of Mr. B On initial psychiatric consultation Mr. B denied being ill or needing care. He wanted to return home to live with his partner. He had impairment of memory, abstract thinking, planning, and executive function. Mr. B had anosognosia, constructional apraxia on clock and Bender drawings, psychomotor retardation, and profoundly diminished intellectual functioning relative to his educational (MBA) and occupational levels. He was incontinent of urine and feces.

  39. Diagnosis and Treatment of Mr. B Mr. B met criteria for HIV-associated dementia (HAD). After two years of directly administered ART in the nursing home setting, evidence of HAD could not be detected on psychiatric examination. Mr. B was able to resume independent living and went from disabled young man in diapers to dapper investment banker. Dementia can occur at any age in persons with HIV infection. Early treatment with ART and early recognition of HAND can lead to decrease or resolution of cognitive impairment and restoration of function in some persons with HIV/AIDS.

  40. Diagnosis and Treatment of HAND This vignette illustrates that although ART has had a major impact on both morbidity and mortality in persons with AIDS, HAND is still prevalent and is the most common treatable cause of dementia in persons under 50 (Ances and Ellis, 2007) It is important to diagnose HIV infection early and begin ART, since there is evidence that HIV has an affinity for neural tissue and can establish independent reservoirs in the brain Every person with HIV infection needs a comprehensive evaluation for cognitive impairment at baseline and at least twice yearly to ensure early diagnosis and of HAND Comprehensive psychiatric assessment for HAND and other psychiatric disorders in persons with HIV and AIDS is described in the Handbook of AIDS Psychiatry HAND is a prevalent diagnosis young persons as well as in elderly persons with HIV/AIDS

  41. HIV-Associcated Neurocognitive Disorder (HAND) HAND is found in 69% of virally suppressed persons with HIV (Simioni et al. 2010) Current estimates of HAND prevalence is 40% - 50% (CHARTER 2014) Neurocognitive disorders can resemble depression and are seldom diagnosed Diagnosis requires complete cognitive assessment but brief screening can help lead to diagnosis HAD leads to nonadherence with HIV care HAD may reverse with ART Once treated, adherence improves, preventing illness progression

  42. Screening for HIV-Associated Neurocognitive Disorders (HAND) The gold standard is a full battery of neuropsychological testing administered by a neuropsychologist Unavailable in most clinical settings Often available only as part of a research study Unavailable in resource-limited settings Efforts are made to develop reliable and valid screening tools but no screening tool has been identified thus far

  43. HIV-Associated Neurocognitive Disorders: Screening with Simioni Questions Do you experience frequent memory loss - do you forget the occurrence of special events even the more recent ones? Do you feel that you are slower when reasoning, planning activities, or solving problems? Do you find it more difficult to perform activities that used to be automatic for you (paying bills, writing checks, making plans) Do you have difficulties paying attention (to a conversation, a book, or a movie)? Do you have difficulty with complex learned tasks that were previously easy for you (playing the piano, speaking a second language, knitting a sweater)? Simioni et al, AIDS 2010 - adapted with additions

  44. HIV-Associated Neurocognitive Disorders: The Use of Screening Tools is Controversial The HIV Dementia Scale (HDS) was developed to screen for HAD The International HIV Dementia Scale (IHDS) was developed for global use The Montreal Cognitive Assessment (MoCA) was developed to screen for HAND but reliability and validity are not adequate Power C, Selnes OA, Grim JA, McArthur JC. HIV Dementia Scale: a rapid screening test. J Acquir Immune Defic Syndr Hum Retrovirol 1995; 8:273 278 Sacktor NC, Wong M, Nakasujja N, Skolasky RL, Selnes OA, Musisi S, et al. The International HIV Dementia Scale: a new rapid screening test for HIV dementia. AIDS 2005; 19:1367 1374 Koski L, Brouillette MJ, Lalonde R, Hello B, Wong E, Tsuchida A, et al. Computerized testing augments pencil-and-paper tasks in measuring HIV-associated mild cognitive impairment. HIV Med 2011; 12:472 480

  45. HIV-Associated Neurocognitive Disorders: The Use of Screening Tools is Controversial Zipursky AR et al. Evaluation of brief screening tools for neurocognitive impairment in HIV/AIDS: a systematic review of the literature. AIDS 2013; 27:2385 2401. There is no adequate, reliable, valid screening tool for the diagnosis of HAND

  46. Controversy in Diagnosis of HAND No reliable and valid screening instrument has been developed as yet The best approach is neuropsychological testing can be abbreviated and utilized Do not use the Mini Mental State Examination Can use the Simioni questions and clock drawing for a baseline and semiannual assessment

  47. Controversy in Treatment of HAND: How Important is CPE Rank? Initially thought to be important, the ability of ART to cross the blood brain barrier, or the CNS penetration effectiveness (CPE) rank is now in question Is lowering CNS viral load correlated with clinical improvement? Letendre S et al. Arch Neurol 2008;65:65 Caniglia EC et al. Neurology 2014 Ellis RJ et al. CID 2014;58:1015.

  48. Treatment of Psychiatric Disorders in Persons with HAND Crisis Intervention Individual psychodynamic psychotherapy Supportive psychotherapy Cognitive behavioral therapy Group psychotherapy Couple therapy Family therapy Bereavement therapy Substance use treatment Palliative psychiatry Psychoeducational approaches to prevention Psychopharmacology

  49. Treatment of Psychiatric Disorders in Persons with HAND: Support Groups Provide a safe environment to discuss concerns about HIV, its stigma, and its treatments Provide support from both members and leaders Confidential Non-judgmental Compassionate Caring All in the same boat Acceptance and sense of family

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