Neuropsychiatric Aspects of HIV_025557.pptx

Important one

1. Neuropsychiatric Aspects of HIV Presenter- Dr. Sunil Regmi Moderater - Dr Sucheta Saha Chairperson- Dr Vijay Krishnan

2. Intro Epidemiology Risk factors pertinent to psychiatric conditions Psychiatric disorders common in HIV Treatment approach Drug Interaction of ARV and Psychotropics Stigma New Challenges like Chemsex HIV survival double edged sword Counselling Conclusions Bibliography Overview

3. Originated from primates in Africa HIV/AIDS discovered in 1981 in gay population Retrovirus, HIV I (80%) & HIV II Single strand RNA virus belonging to Retroviridae family Multiply by reverse trasnscriptase in host white cells AIDS is the most advanced stage of infection Introduction

4. Unprotected anal intercourse- 1.4% Unprotected vaginal sex- 0.8% Contaminated needles to inject drugs- 0.67% Occupational needlestick injury- 0.24% Blood Transfusion- >90% Mother-to-child Not on ART- 25% On ART- 0.8% Routes of Transmission

5. Infect the immune cells CD4+ T-cells and macrophages CD 4 <200/µL vulnerability to opportunistic infections Clinical stages Asymptomatic HIV infection Mild symptomatic stage Moderately symptomatic stage Severely symptomatic stage or AIDS Chronic disease for most of the patient after advent of HAART Pathogenesis

6. Disease Progression

7. Estimated 39.0 million people worldwide living with HIV at the end of 2022 1.5 million are children below 15 yrs Since 2010, the number of people acquiring HIV has been reduced by 38% SEAR 3.9 millions 2.40 millions in India (NACO 2021) Epidemiology of HIV WHO 2022

8. PSYCHIATRIC CONDITIONS IN THE HIV

9. Bidirectional Psychiatric disorders play several roles in the HIV transmission, in elements of treatment, and in co-morbidity Co-relation Nedelcovych et. al., May 2017

10. Health anxiety Pretest Anxiety Post test stress Vulnerable individuals like victims of abuse Secondary opportunistic infections/ tumors of CNS Context of arising Psychiatric Problems Oxford handbook, 4 th edition

11. Untreated Mental Illness can be important vector More likely to engage in high risk behaviour Sex and substance use in unsafe way and in more frequency Decreased access to care Decreased adherence to HIV therapies Increased medical comorbidity Treatment of mental illness is considered as prevention strategy Mental Illness and HIV transmisssion

12. H/O psychiatric disorder preceding HIV CNS HIV infection CNS opportunistic illnesses and cancers Substance intoxication and withdrawal Neuropsychiatric complication of HCV infection and its treatment S/E of HIV medication Drug-drug interaction Endocrinologic abnormalities D/D of Psychiatric disorders in Patients with HIV

13. Myer et. al., 2008, South Africa Nedelcovych et. al., 2017,USA A cross-sectional study in Ethiopia revealed upto 28% had common mental disorders Another cross sectional study in South Africa shows the prevalence of depression, PTSD and alcohol dependence or abuse was 14% , 5% & 7% respectively Similarly, a study in USA revealed Substance Use 40−74% Depression 22−50% Anxiety Disorders 2−40% PTSD ∼30% Sleep Disturbance 10−50% Severe Mental Illness/Psychosis 0.2−15% High Rates of Psychiatric Complications in HIV/ AIDS Patients

14. Mostly acquire the infection from maternal transmission Vulnerable to growing up in stressful environment Parents death Stigma Poor social support 45% had a lifetime prevalence of any psychiatric illness Depression, anxiety, disruptive disorders and hyperactive disorders are common Psychiatric comorbidity in HIV infected children Rao et. al.

15. Transitory syndrome after knowing the positive status Generally melts down within hours to days Can present altered behaviour, panic attacks or social isolation Acute Stress Reaction

16. Prevalence of depression and anxiety among HIV patients was 41.2 % and 32.4 % respectively and both 24.5% d/d Non pathological state of grief and mourning and d/o related to both psychological and physiological disturbances Dysthymia, dementia, delirium, demoralization, intoxication, withdrawal(cocaine), CNS injury or infection, acute medical illness, etc. CNS syphillis Depression Tesfaw et. al., 2016, Ethiopia

17. Risk Factors Chronicity of the illness with huge psychological burden Significant losses and isolation Complex medical treatments( medication that alter the mental function) Comorbid neurological illness Comorbid substance use ...Depression

18. Rather than Drug itself, adequate dose and duration of treatment determines improvement. General rule “start low and go slow to a full dose or therapeutic serum level) Managing side effects is vital for adherence Augmentation ( Lithium, T 3 , atypical neuroleptics , or an alternative t/t) Psychotherapeutic Treatment Treatment

19. 3% to 44.4% including various types of anxiety disorder has been seen Increased risk of GAD, panic disorder, PTSD and OCD Mostly comorbid with depression Anxiety Disorder Brandt et al, Clin Psychol Rev. 2017 Feb Chandra et al, 1996, India

20. Life threatening traumatic events provoke terror, anxiety and stress in most individuals often leading to PTSD Women & Adolescents are more vulnerable PTSD among HIV-positive women is 30% , which was over 5 times national sample Comorbid psychiatric d/o is upto 80% depression substance use sexual promiscuity or prostitution PTSD or traumatic stressors symptoms a/w lower CD 4 T cell count Simultaneous treatment of concurrent conditions is a must PTSD Risk factors for HIV Machtinger et al, 2012, USA

21. 70-80 % throughout the course of infection Classify based on severity Asymptomatic Neurocognitive Impairment(ANI) Mild Neurocognitve disorder(MND) HIV associated Dementia (HAD) CD 4 count, opportunistic infections and viral load contribute to the risk Higher medical comorbidity- increased severity Rates of HAND are still remarkably high, though HAD has declined after HAART Aging of HIV infected population is a confound HIV associated Neurocognitive Disorder(HAND)

22. Involves Cortical loss impairment in memory(learning) and executive function like that of Alzheimer disease And subcortical loss impairments in motor skills, cognitive speed and verbal fluency International HIV Dementia Scale or MoCA After CART- Incidence has markedly declined No clear effective t/t has emerged till date ...HAND

23. Previously termed AIDS Dementia complex Vs CMV encephalitis, PML, cerebral toxoplasmosis, cryptococcal meningitis, CNS lymphoma HIV itself can be the causative factor Present with Cognitive, Motor or Affective symptoms HAART can slow progression Mean survival after HAD is 6 months HIV Associated Dementia (HAD)

24. Occurs in upto 30% patients with AIDS Older age and Patients with HIV associated Dementia(HAD) are at increased risk Either direct infection of the brain or sec. Infection D/D AIDS mania Major depression Bipolar depression Panic disorder Schizophrenia Substance withdrawal Delirium Oxford handbook, 4 th edition

25. Often a/w substance abuse and impulsive behaviour Risk factor for spreading of infection “garden variety” vs AIDS mania Bipolar(Manic-Depressive)

26. Late stage HIV infection A/w cognitive impairment and lack of previous episodes and family history 8% of all patients with AIDS Comorbid dementia or other cognitive impairment indicating brain damage were often seen. AIDS Mania

27. AIDS mania vs Bipolar Mania More cognitive slowing and dementia Irritable mood Prominent psychomotor slowing Severe and malignant Less seen Euphoria Hyperactivity Less

28. Early stage of HIV Mood stabilizer, anticonvulsants and antipsychotic agents Advanced HIV With low CD 4 counts Double edge sword with antipsychotics (preferred atypical ) Lithium is problematic (high rates of delirium, cognitive difficulty, GI symptoms, DI, combination with Tenofovir (renal s/e), rapid fluctuation in blood level) Valproic acid has been success( Hepatotoxicity , hematopoietic) Lamotrigine ( rashes, SJS) Carbamazepine - sedation, bone marrow suppression Gabapentine , oxcarbazepine , and topiramate can be tried Treatment AIDS Mania

29. No evidence HIV causing schizophrenia but SCZ causes behaviour lead to HIV infection High risk sexual behaviour, injecting drug usage,etc Risk Behaviours Questionnaire(RBQ) can be applied Treatment principles are same but close ties with HIV care providers is vital ARV same but recommended avoiding EFAVIRENZ- based regimen Schizophrenia

30. Substance is a primary vector for the spread of HIV Injection drug users as well as disinhibited & impulsive act under intoxication leading to unsafe sexual practices Issues with attachment to health care services and compliance to long term treatment Vulnerability due to Psychiatric, psychological and personality factors. Co- occurring medical problems like chronic pain, opportunistic infections and surgical procedures may cause exposure to opioids or sedatives which can lead to addiction Substance use Disorder

31. Medical implications of ongoing substance use Overlapping symptoms of HIV infection and substance intoxication/withdrawal Chronic use increased immunocompromised state and medical sequelae IDUs contract other bacterial infections and predispose to TB, STDs, viral hepatitis, etc. Lymphoma more frequent in HIV infected drug users SUD and HIV

32. Alcohol users has faster progressions of HIV disease and poorer response to ARV therapy Active substance use is highly a/w nonadherence and reduced access to ARV medication Neurological symptoms can overlap AIDS dementia & drug intoxication (apathy, disorientation, aggression & altered consciousness) Drug withdrawal & opportunistic CNS infections IDU with HIV higher risk for brain spinal cord fungal and bacterial infections Alcoholics of older age vulnerable to cognitive decline ...SUD and HIV

33. General standards of treatment principals Mindful of ARV & abused substances interaction. Eg Didanosine causing peripheral neuropathies worsened by alcohol use Opioid users on methadone- Rifampicin and other ARVs increases the elimination leads to withdrawals necessitating dose adjustments Buprenorphine is promising with minimal interaction Treatment of SUD

34. Dual Diagnosis Drug use disorder with another co-occurring psychiatric disorder Triple Diagnosis Dual diagnosis patient who also has HIV infection

35. Effects of Drugs Symptoms spectrum Implicated agents Depression Efavirenz , Raltegravir , IFN- α , steroids, Isoniazid Mania Didanosine , Efavirenz , Zidovudine Psychosis Abacavir , Efavirenz , Acyclovir, INH, Steroid Anxiety Didanosine , Gancyclovir Vivid Dreams Abacavir , Nevirapine , Efavirenz Suicidal ideation Abacavir , Efavirenz Peripheral Neuropathy Didanosine , Stavudine

36. Interactions Enzyme Inhibitors Effects Fluvoxamine (CYP1A2/CYP3A4) Protease Inhibitors(PI) toxicity ↑NNRTI Fluoxetine , Sertraline & paroxetine (CYP2D6) Protease Inhibitors toxicity Ritonavir (CYP 3A4) Increased BZDs leading to oversedation or respiratory depression Ritonavir Clozapine , Pimozide . Also other antipsychotics Ritonavir ( CYP 2D6 ) Augment levels fluoxetine , citalopram , paroxetine , and sertraline with reported cases of serotonin syndrome Darunavir (CYP 3A4) ↑ Risperidone , Quetiapine , Aripiprazole , Trazodone Nelfinavir (CYP 3A4,CYP2B6) ↑ Bupropion Efavirenz , Nevirapine (CYP3A4) ↓ Carbamazepine ( ↑ by PI)

37. Bidirectional relationship- sleep and immunity. Also with emergence of HAART, ageing & comorbidity is added risk factors Self reported sleep disturbance is upto 58% Insomnia, OSA and poor quality sleep are common Early stages of infection, sleep-promoting cytokines could mediate sleep disturbances Chronic immune activation, in addition to side effects of ARVs, may impact sleep homeostasis further contribute to an inflammatory state Sleep Disturbances

38. Prevalence of 19-36% among HIV infected and 15-20% HIV at risk population ( vs general population rate 10%) ASPD the most common HIV infected with persistent High Risk Behaviours has been the major challenge Sex and drug risk behaviours Knowledge is not enough for these individuals Effective prevention and treatment programs must consider specific personality factors ISSUES OF PERSONALITY

39. Extraversion Sexual promiscuity Desire for sexual novelty Multiple sex partners Neuroticism Unprotected anal sex Psychoticism Multiple sexual partners and unprotected sex Personality traits and Risk Behaviours Drug and Alcohol Addictions

40. HIV is a significant risk factor Immediate psychological reaction, Chronic recurrent illnesses/infections, P/H/O Psychiatric illnesses and suicidal behaviour Co-morbid depressive, anxiety behaviours is added risk factors Suicide risk assessment is recommended whenever potential risk is apparent. Suicide

41. Upto 80% of patients experience chronic widespread pain( polyneuropathy ) or chronic headache HIV itself or drug induced peripheral neuropathy & chronic inflammation Often leading to frequent self medication eg opioids putting them at risk of substance dependence Decreased quality of life and a high rate of disability Chronic Pain

42. Viewed as deviant from social standards as immorality, promiscuity, perversion, contagiousness Mainly due to inequality in economy & gender, lack of knowledge and socio-cultural norms Stigmatised individuals -feelings of shame and guilt Women are more vulnerable to stigma HIV/AIDS related stigma can be Self stigma- self blame and self deprecation Perceived stigma- fear of disclose of infection(97%) Enacted stigma- actively discriminated due to HIV status(26%) Joining the support group helps decreasing stigma Stigma attached with HIV Infection Thomas et al, AIDS care, Oct 2005 NACO

43. Chemsex is use of drugs in sexual contexts  to facilitate, initiate, prolong, sustain, or intensify the sexual encounter Mostly among gay, bisexuals or MSM Seen in more than 4 % visiting to HIV clinic and 9.9 to 93.7% among MSM Use of potent drug like methamphetamine Potentially harmful drug interactions with ARVs ( ritonavir and cobicistat ) Also involves intoxication & overdose HIV and Chemsex Alder et al, HIV Med, Aug 2022 Strong et al, Lancet HIV, Oct 2022

44. Needle and syringe programs Promote access to condoms, safer-sex advice Access to HIV and STI testing Post exposure or preexposure prophylaxis Support noninjecting routes of administration Sociocultural strategies and sexual health promotion before, during, and after a chemsex session Self-control coaching to support safer patterns of drug use and safer sex Harm Reduction WHO/ UNAIDS, Technical guides, 2019

45. Only 50 % adhere Challenges Long t/t duration Preventive rather than curative Asymptomatic period Frequent and complex medication dosing Neuroticism, extraverted and unstable increasingly have adherence issue Missed doses of HAART implicates the HIV resistance Cognitive behavioural approach proves to be effective in treatment of such personalities. Adherence to Medication

46. Pretest HIV counselling Meaning of positive and negative result. Discuss and explore patient's fear, concern and potential reactions to severe stresses. Addressing confidentiality concern regarding test and the result Explore High Risk behaviours and recommend risk reducing advices. Documentation of discussion Allowing the patient to ask questions Role of Counselling in HIV

47. Test result interpretation- clarifying distortion Assess understanding and emotional reaction Preventive measures for avoiding transmission Health check up/testing of sexual partner and needle contacts Consider individual or group supportive therapy for psychological assistance Shock of the diagnosis, fear of death, social consequences, grief of potential losses and mention the positive hopes Look for depression, hopelessness, anger, frustration, guilt, impulsive or suicidal thoughts Posttest counselling

48. Often disregarded in HIV clinic for medical decisions for their healthcare HIV dementia and delirium, intoxication or in psychotics it can be overlooked Complicated when cognition present but judgement is colored by affective state, temperament, drug cravings, social situations or simply intolerable discomfort. Capacity to consent

49. Most important factor of treatment outcome Psychiatric issues are major factors the issue Interventions as below is helpful CBT supportive psychotherapy Group interventions Technical interventions like pill box, timer reminder decreased pill burden and increased access to care helps. Adherence Counselling

50. ART has revolutionized the HIV outcomes 20 yr old HIV + ve on ART in the USA or Canada has a life expectancy approaching that of the general population Stigma, loss of friends & social networks, and the detrimental effects that HIV and ARV on aging. More likely to experience mental health and neurocognitive impairment Older LGBT adults are more likely to have experienced mistreatment and discrimination with higher rates of anxiety, depression, and substance use disorders  Treatment fatigue and tolerability Chronic ailments like HTN, DM, cancer, HCV are more common compared to general population Good Prognosis of HIV but.... Kart and Maughan -Brown, Lancet HIV, Aug 2023

51. HIV/AIDS and Psychiatry are intimately linked Psychiatric d/o seen as vectors of transmission and complicating the treatment HIV produces/exacerbates many psychiatric conditions HIV can be seen as a model to role of psychiatry in general medicine and health care Comprehensive diagnostic formulation has to be developed for successful treatment Conclusions

52. Bibliography Sadock B J, Sadock V A, Ruiz P. Kaplan & Sadock’s Synopsis of Psychiatry, 11th ed. Wolters Kluwer . 2015 Nedelcovych MT, Manning AA, Semenova S, Gamaldo C, Haughey NJ, Slusher BS. The Psychiatric Impact of HIV. ACS Chem Neurosci . 2017 Jul 19;8(7):1432–4. O’Brien KE, Riddell NE, Gómez-Olivé FX, Rae DE, Scheuermaier K, von Schantz M. Sleep disturbances in HIV infection and their biological basis. Sleep Med Rev. 2022 Oct;65:101571 David Semple , Roger Smyth. Oxford Handbook of Psychiatry, 4 th Edition, Oxford University Press. 2019 Jayarajan N, Chandra PS. HIV and mental health: An overview of research from India. Indian J Psychiatry. 2010 Jan;52(Suppl1):S269–73 Myer L, Smit J, Roux LL, Parker S, Stein DJ, Seedat S. Common mental disorders among HIV-infected individuals in South Africa: prevalence, predictors, and validation of brief psychiatric rating scales. AIDS Patient Care STDS. 2008 Feb;22(2):147–58 Addis DR, DeBerry JJ, Aggarwal S. Chronic Pain in HIV. Mol Pain. 2020 Jan 1;16:1744806920927276. McArthur JC, Brew BJ. HIV-associated neurocognitive disorders: is there a hidden epidemic? AIDS. 2010 Jun 1;24(9):1367. Nosik M, Lavrov V, Svitich O. HIV Infection and Related Mental Disorders. Brain Sci. 2021 Feb 17;11(2):248.