Eleven Things About HIV_AIDS Training Directors Need to Know

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 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 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 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 drugdrug interactions • Application of principles and skills to other neuropsychiatric disorders 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 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 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. <2 missed doses per week) to achieve optimal outcomes • Psychiatric D/o’s, especially Mood, Anxiety, & Adjustment D/o’s significantly impact tx readiness/adherence • Active Substance Abuse/Dependence, particularly cocaine/crack, has a negative impact on readiness/adherence 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 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/attitudes 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/saving 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 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 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 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 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 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) 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) 3. Neuropsychiatric vs. Psychiatric Disorders • Distinguishing Neuropsychiatric vs. Psych D/o’s – 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 Distinguishing Neuropsychiatric vs. Psych D/o’s • 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 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 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/e’s include severe depression, mania, suicidal ideation, paranoia, psychosis, anxiety • CNS s/e’s include drowsiness, insomnia (+/abnormal dreams), impaired concentration 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®, DepoTestosterone®), in addition to tx for depression 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 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) 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 OI’s 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 8. Antipsychotic Medication & HIV In HIV+ patients: – Tx with “traditional” high-potency antipsychotic medications, may lead to greater risk for extrapyramidal side effects (dystonic rxn’s, 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” 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 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 PI’s lead to increased levels of benzos and sildenafil 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 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 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 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 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 – 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“ 11. Psychological Responses to Physiological/ Metabolic Changes • HIV- related lipodystrophy syndrome • Managing Adherence to Anti-HIV meds – Ambivalence – Uncertainty – Delayed gratification • Grieving and Loss Acknowledgments Khakasa Wapenyi, MD Joseph Murray, MD Milton Wainberg, MD Arkady Bilenko, MD Wade Leon, NP Francine Cournos, MD Candice Peggs Steve Ferrando, MD