Eleven Things About HIVAIDS Training Directors Need to Know and Teach Residents

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Eleven Things About HIV/AIDS Training Directors
Need to Know and Teach Residents

• Marshall Forstein, M.D.
• Adult Psychiatry Training Director, The Cambridge
  Health Alliance,
• Harvard Medical School
• Warren Liang, M.D.
• Psychiatry Training Director,
• University of Cincinnati School of Medicine

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Objectives

• To discuss why the teaching of HIV psychiatry is
  important
• To present some basic issues for training
  directors to consider to insure HIV psychiatry is
  part of the residency curriculum
• To present suggestions for using the HIV/AIDS
  Neuropsychiatric Curriculum in a residency program

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Context of the Pandemic

• Psychiatric patients at increased risk for HIV
• Patients who experience stigma and social
  marginalization have decreased access to medical
  as well as mental health care
• Comorbid disorders are the norm, not the
  exception
• People with HIV have opportunities for increased
  longevity but psychiatric disorders and social
  stigma may preclude chronic management of the
  disease

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HIV/AIDS as Paradigm understanding the interface
of Mind, Brain and Body

• Real value in preparing psychiatry residents for
  clinical practice
• Sexual and drug use risk assessment skills
• Neuropsychiatric screening and evaluation
• Application of co-morbid treatment options
• Managing complex medical/psychiatric disorders
• Enhancement of psychopharmacologic understanding
  of drug-drug interactions
• Application of principles and skills to other
  neuropsychiatric disorders

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Applying the Bio-Psycho-Social Model

• BIO HIV invades the Central Nervous System soon
  after infection
• protean manifestations of neurological and
  psychiatric disease
• PSYCHO psychiatric disorders are increased in
  people with HIV, and people with psychiatric
  disorders have increased risks for acquiring HIV
  infection
• SOCIAL People with HIV disease continue to be
  stigmatized, marginalized and have many social
  problems that interfere with adequate mental
  health and medical care

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Outline

• Evaluation Assessment
• 1. Stages of Change Model
• Diagnostic concerns
• 2. AIDS Mania
• 3. Neuro vs. Psych Disorders
• 4. CNS side effects of Sustiva
• 5. Hypogonadism and depression
• Treatment issues
• 6. AIDS Dementia
• 7. HIV Psychosis
• Psychopharmacology
• 8. Antipsychotics and HIV
• Drug interactions
• 9. P450 Drug Interactions
• 10. Ritonavir (Norvir) , and Ritonavir/lopinavir
  ( Kaletra) drug interactions
• Lipodystrophy syndrome
• 11. Impact of metabolic changes on psychological
  and social function

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1. Stages of Change HIV Treatment Readiness
Adherence, Substance Abuse

• Psychiatrists role in assessment of HIV tx
  readiness adherence becoming more recognized
  integrated
• HIV tx recommendations when starting HAART,
  expectation to achieve 95 adherence with tx
  regimes (i.e. achieve optimal outcomes
• Psychiatric D/os, especially Mood, Anxiety,
  Adjustment D/os significantly impact tx
  readiness/adherence
• Active Substance Abuse/Dependence, particularly
  cocaine/crack, has a negative impact on
  readiness/adherence

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1. Stages of Change HIV Treatment Readiness
Adherence, Substance Abuse

• Transtheoretical Model (DiClemente Prochaska)
  of Stages of Change can be incorporated into
  psychiatric assessment tx of HIV pts with HIV
  treatment concerns/ambivalence and/or substance
  abuse
• Stages of Change
• Precontemplation
• Contemplation
• Action
• Maintenance
• Termination or Relapse/recycle

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1. Stages of Change to Assess HIV Treatment
Readiness Adherence, Substance Abuse

• Objective is Harm Reduction
• Assess stage, then help patient through
  motivational interviewing/enhancement (Miller) to
  work through the stages of change towards more
  healthy adaptive behaviors self-beliefs/attitu
  des

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1. Stages of Change HIV Treatment Readiness
Adherence, Substance Abuse

• Conceptualized as a cycle engagement in tx as
  essential
• HIV Tx Readiness/Adherence
• r/o psychiatric d/o or substance abuse, rx
  accordingly
• pts may not be ready to start life-enhancing/savin
  g tx, but will have greater understanding of
  motivation
• Substance Abuse/Dependence
• Model may be used by psychiatrists to engage pt,
  and prepare for substance abuse tx or may be used
  as part of substance abuse tx itself
• Relapse seen as part of the cycle, not an
  indication for tx termination

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2. AIDS Mania

• Differs from idiopathic Bipolar Disorder in that
  pt often has no personal or family h/o Bipolar
  Disorder
• Similar symptomatology DIG FAST, except mood
  mood is usually more irritable than euphoric
• Often associated with late-stage HIV disease/AIDS
  or AIDS Dementia
• Can be medication or drug-induced AZT, steroids,
  stimulating illicit drugs (cocaine, CM, speed,
  steroids)
• May be associated with CNS involvement
• Risperidone has been shown to be effective in
  treating AIDS Mania, with minimal adverse effects

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3. Neuropsychiatric vs. Psychiatric Disorders

• Neuropsychiatric syndromes may be confused with
  Psychiatric Disorders, especially Mood Disorders
• Neuropsychiatric syndrome complaints may mimic
• Depression apathy, memory changes,
  sleep/energy/appetite changes, functional
  impairment, low mood, social withdrawal, paranoia
• Mania restlessness, distractibility, memory
  changes, decreased sleep, irritability, impaired
  judgment, paranoia

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3. Neuropsychiatric vs. Psychiatric Disorders

• Psychiatric Disorders commonly associated with
  HIV/AIDS
• Mood Disorders
• Adjustment Disorders
• Anxiety Disorders
• Psychotic Disorders
• Substance Abuse Disorders
• Pain Disorders

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3. Neuropsychiatric vs. Psychiatric Disorders

• HIV Neuropsychiatric complications include
• AIDS Dementia (HIV-1 associated Dementia)
• Minor Cognitive-Motor Disorder (MCMD aka Minor
  AIDS Dementia)
• Delirium
• Amnestic Disorders

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Minor Cognitive-Motor Disorder

• American Academy of Neurology, 1991
• Two of
• Impaired attention/concentration
• Mental slowing
• Impaired memory
• Slowed movements
• Impaired coordination
• Personality change/irritability/lability
• Neuro exam (impaired SPEM, hyperreflexia,
  frontal release, slowed RAM, ataxia)

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HIV Cognitive Disorders

• Classification by American Neurological
  Association
• Minor Cognitive Motor Disorder
• 14 of patients with early HIV
• 24 of patients with late HIV
• HIV-Associated Dementia
• Comparable to CDC-defined HIV encephalopathy
• 7-10 of patients with late HIV (21 pre-HAART)

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3. Neuropsychiatric vs. Psychiatric Disorders

• Distinguishing Neuropsychiatric vs. Psych D/os
• Prominent memory and cognitive (executive
  functioning, task completion) difficulties
• Problems with motor function (visuospatial
  difficulties, impaired coordination)
• Speech/language problems (aphasias, parapraxis)
• Fluctuating levels of consciousness/alertness
  acute disorientation
• New onset psychosis (particularly visual other
  non-auditory hallucinations)
• Personality changes

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Distinguishing Neuropsychiatric vs. Psych D/os

• Assessment includes
• careful history mental status
• neurological exam, neurological work-up may
  include neuroimaging, LP, labwork,
• neuropsychological testing
• Differential diagnosis includes
• CNS complications (HAD, MCMD, delirium,
  infections, lymphoma)
• Medical conditions (endocrine, metabolic
  disorders)
• Medication-induced disorders
• Substance-related disorders

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4. Psychiatric/CNS Side Effects of efavirenz
(Sustiva)

• Efavirenz, a non-nucleoside reverse transcriptase
  inhibitor (NNRTI), may be used as part of a HAART
  regimen
• Similar to steroids in the range of psychiatric
  symptoms which may be induced

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4. Psychiatric/CNS Side Effects of efavirenz
(Sustiva)

• Psychiatric side effects are common
• Controlled trial of 1,008 pts taking efavirenz,
  635 experienced significant psychiatric adverse
  effects requiring intervention
• Psychiatric s/es include severe depression,
  mania, suicidal ideation, paranoia, psychosis,
  anxiety
• CNS s/es include drowsiness, insomnia (/-
  abnormal dreams), impaired concentration

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5. Hypogonadism and Depression

• When evaluating depressive disorders (Major
  Depressive D/o, Dsythymic D/o, Depressive D/o
  NOS, Adjustment D/o w/depressed mood) in HIV
  men, check testosterone levels, r/o hypogonadism
• HIV men have a greater risk of
  hypotestosteronism than the general population
• Tx of hypotestosteronism consists of testosterone
  replacement (Androderm, Androgel,
  Depo-Testosterone), in addition to tx for
  depression

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5. Hypogonadism and Depression

• The jury is out about any association between
  hormones levels and depression in women
• Hypotestosteronism in HIV transgendered
  depressed patients (male-to-female) must be
  evaluated treated on a case-by-case basis

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6. AIDS Dementia (HIV-1 Associated Dementia aka
HAD)

• Tx primarily consists of antiretroviral
  medication
• Subcortical dementia with deficits in affect
  (dysphoria, blunted), behavior, cognition and
  motor function
• Cannot be diagnosed using Mini-Mental Status Exam
• Use HIV Dementia Scale, Memorial Sloan Kettering
  Rating Scale, Blessed Dementia Scale,
  Neuropsychological Testing
• Medication management (which may include
  psychostimulants, neuroprotective
  anti-inflammatory mediators, immunostimulants,
  nutritional interventions) with vigilance towards
  monitoring adherence, symptomatic tx
  (psychosis, insomnia, aggression, memory problems)

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7. HIV Psychosis

• Often more difficult to treat than other forms of
  psychosis, both diagnostically
  pharmacologically
• Etiology of HIV Psychosis
• Psychosis arising in HIV pt with a pre-existing
  psychotic disorder
• HIV-1 infection, or secondary opportunistic
  infections, may precipitate psychosis
• Comorbid substance abuse may induce psychosis
• Psychosis may be induced by medications used to
  HIV infection or OIs

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7. HIV Psychosis

• Treatment with antipsychotic medications
  adjunctive medications can be problematic
• Use of benzodiazepines for adjunctive tx may lead
  to adverse effects such as paradoxical agitation,
  greater cognitive difficulties /or dependence

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8. Antipsychotic Medication HIV

• In HIV patients
• Tx with traditional high-potency antipsychotic
  medications, may lead to greater risk for
  extrapyramidal side effects (dystonic rxns,
  parkinsonian syndrome, akathisia, akinesia, TD,
  catatonia, NMS)
• Tx with low-potency antipsychotic medications,
  including atypicals, may be more associated with
  anticholinergic side effects (which may
  exacerbate delirium)
• rule of thumb start low (i.e. reduce initial
  dose by 50) and go slow

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9. Cytochrome P450 Drug Interactions

• All Protease Inhibitors (PIs) Non-Nucleoside
  Reverse Transcriptase Inhibitors (NNRTIs) are
  substrates of cytochrome P450
• Therapeutic concerns some psychotropic
  medications (i.e. TCAs) and antiretrovirals
  (ARVs) may have narrow therapeutic indices
  (including PIs NNRTIs)
• Drug interactions b/n psychotropic medications
  ARVs may lead to resistance to not just the
  specific ARV, but all within the same drug class

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PI Drug Drug Interactions

• PI inhibition of 3A can lead to Fentanyl
  toxicity( a substrate for 3A )
• Ritonavir induces glucuronyl transferase (which
  metabolizes benzodiazepines), leading to
  decreased bioavailability of a benzo
• 3A inhibition by nefazodone and PIs lead to
  increased levels of benzos and sildenafil

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9. Cytochrome P450 Drug Interactions

• P450 Inhibitors (by level of potency)
• Significant ritonavir
• Moderate indinavir, nelfinavir, amprenavir,
  delaviridine
• Weak saquinavir
• P450 Inducer nevirapine (3A4)
• P450 Inhibitor Inducer efavirenz (Sustiva)
  3A4
• Co-administration of NNRTIs (efavirenz,
  delaviridine, nevirapine) and certain
  psychotropic medications (fluoxetine,
  fluvoxamine, nefazodone) may lead to toxic levels
  of NNRTIs

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10. Drug-drug Interactions and Norvir Kaletra

• lopinavir/ritonavir (Kaletra) , is the only
  combination PI, having ritonavir (Norvir ) as
  one of its components
• Ritonavir (Norvir ) is the ARV with the most
  potential for clinically significant psychotropic
  drug interactions
• Ritonavir is a potent cytochrome P450 3A4, 2D6,
  2C9, 2C19, 2A6, 1A2 2E1 inhibitor
• As with antipsychotic medications, when combining
  Norvir or Kaletra with psychotropics, it is
  safer to start low go slow

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10. Drug-drug Interactions and Ritonavir (Norvir
) Ritonavir/lopinavir (Kaletra)

• Psychotropics contraindicated due to risk of
  toxically increased drug levels
• clozapine, pimozide (incr. risk of QT interval
  prolongation), midazolam triazolam (incr. Risk
  CNS depression)
• Psychotropics with risk of increased drug levels
  reduce initial dose by at least 50
• TCAs, SSRI, bupropion, venlafaxine, maprotiline,
  trazodone, haloperidol, risperidone,
  thioridazine, chlorpromazine, ziprasidone,
  aripiprazole, buspirone, lamotrigine, zolpidem,
  diazepam, flurazepam
• nefazodone, sertraline (greater risk, reduce
  initial dose by 70)
• Psychotropics that may cause toxic Norvir or
  Kaletra drug levels via metabolic inhibition
• fluvoxamine, nefazodone, paroxetine, sertraline,
  venlafaxine, olanzapine, perphenazine,
  thioridazine

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11. HIV-Associated Lipodystrophy

• body shape and metabolic abnormalities
• 3 main categories
• most obvious altered fat deposits
• Subcutaneous fat shrinks in the arms, legs and
  face
• thin limbs with bulging veins
• facial wrinkling with hollow cheeks

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11.HIV-Associated Lipodystrophy

• new fat bulges
• between and above the shoulder blades (dorsal
  cervical fat pads or "buffalo hump")
• abdominal cavity, surrounding the internal organs
  (truncal adiposity or "protease paunch")
• Breast enlargement also occurs, mostly in women

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11. HIV-Associated Lipodystrophy

• More common changes in fat metabolism
• Hyperlipidemia
• Hyperglycemia
• because fat cells are processing less glucose
  into fat stores
• Insulin production may rise to increase the
  removal of sugar from the blood
• elevated production may or may not successfully
  keep sugar levels below normal
• "insulin resistance

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11. Psychological Responses to Physiological/
Metabolic Changes

• HIV- related lipodystrophy syndrome
• Managing Adherence to Anti-HIV meds
• Ambivalence
• Uncertainty
• Delayed gratification
• Grieving and Loss

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Acknowledgments

• Khakasa Wapenyi, MD
• Joseph Murray, MD
• Milton Wainberg, MD
• Arkady Bilenko, MD
• Wade Leon, NP
• Francine Cournos, MD
• Candice Peggs
• Steve Ferrando, MD