NPM OF HIV and aids manifestation with neurosyphillis

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1. NEUROPSYCHIATRIC Manifestations OF HIV/AIDS Dr. RONAK prajapati 2 ND YEAR RESIDENT department of psychiatry Dr. m. k shah medical college

2. INTRODUCTION The retrovirus subfamily to which HIV belongs is called lentivirus ( lenti : slow) The main disease mediator is the infection and destruction of T4 helper cells or CD4 cells critical in cell mediated immunity. 3 stages – asymptomatic AIDS-related complex (ARC) and finally AIDS. The WHO currently stages HIV by clinical symptoms 1 to 4 with increasing clinical severity. These are not based on laboratory testing but instead on clinical presentation for use in resource limited settings. The term “AIDS” is used to describe the syndrome in which patients develop opportunistic medical conditions.

3. EPIDEMIOLOGY UNAIDS 2020 – 1.7 million – newly infected 38 million – PLHI India – Prevalence – 0.22% Maximum – North eastern states - 0.8 to 3.2 % for unprotected anal intercourse - 0.05 to 0.15 % with unprotected vaginal sex - 0.32 % after puncture with an HIV-contaminated needle - 0.67 % after using a contaminated needle to inject drugs Male-to-male transmission has been the most common route of sexual transmission in North America

4. The populations at highest risk are : Homosexual men Intravenous drug users Female partners of intravenous drug users. Those who trade sex for money / drugs. Health workers

5. ETIOLOGICAL AGENT It has 2 types HIV 1 & HIV 2 , the former causes most human infections. The virus is an icosahedral particle (outer envelope & viral core) RNA virus with 2 major envelope proteins gp120 & gp41 . The main receptor for gp120 is CD4 molecule on T lymphocyte helper cell . HIV is a single-stranded ribonucleic acid (RNA) virus . Carries the enzyme reverse transcriptase (RNA-dependent deoxyribonucleic acid [DNA] polymerase).

6. STIGMA ATTACHED WITH HIV INFECTION : HIV/AIDS stigma is perceived as an individual‘s deviance from socially accepted standards of normality & can include deviances such as immorality, promiscuity, perversion, contagiousness & death. Stigma is socially constructed & is attributable to cultural, social, historical & situational factors . Stigmatised individuals are subjected to feelings of shame & guilt . Women are more vulnerable to the stigma. There are 3 broad types of HIV/AIDS-related stigma. 1. Self stigma - occurs through self blame & self-deprecation. 2. Perceived stigma - related to the fear that individuals have that if they disclose their HIV positive status. 3. Enacted stigma - occurs when individuals are actively discriminated against because of their HIV status.

7. Support groups for AIDS in INDIA – SAATHII (Solidarity & Action Against The HIV Infection in India) - Chennai, ASHA Foundation - Bangalore, THE HUMSAFAR TRUST - Mumbai, Indian Network for People Living with HIV/AIDS(INP+)- Chennai, Save the Children, Bal Raksha , Bharat - Delhi

8. Neuropsychiatric condition with HIV/AIDS Delirium Dementia MDD Bipolar disorder Schizophrenia Personality traits/disorder Substance abuse PTSD

9. DELIRIUM : Prevalence of delirium in Hiv -infected populations has been reported to be b/w 43 to 65 %. Clinical presentations are inattention, disorganized thinking / confusion, & fluctuations in level of consciousness. Emotional changes are common & often unpredictable, & hallucinations & delusions are frequently seen. Acute / sub-acute onset . Risk factors include: Older age Multiple medical problems Multiple medications Impaired visual acuity & Previous episodes of delirium Pts with Hiv -associated dementia (HAD) are at an increased risk to develop delirium.

10. The differential diagnosis of delirium includes : Hiv -associated dementia AIDS mania Minor cognitive–motor disorder Major depression, bipolar disorder Schizophrenia Delirium can usually be differentiated from the above conditions based on its rapid onset, fluctuating level of consciousness, & link to a medical etiology . History of illness, physical examination, relevant investigations, review of all medications are needed. A variety of causes may be found like toxins, metabolic, infectious, cardiovascular, endocrine, pulmonary, traumatic etc. EEG may show diffuse slowing of background alpha rhythm which resolves as confusion clears.

11. Treatment consists of 3 parts: Identification and removal of the underlying cause . Reorientation of the patient by maintaining a normal diurnal variation of light cycles, providing orienting stimuli, such as calendars, clocks, & a view of the outside world, & active engagement & reorientation by staff members, family, & friends. Management of behaviour / psychosis - low doses of high-potency antipsychotic agents. Benzodiazepines should be used with caution.

12. HIV and Cognitive Impairment Viral proteins such as gp120 and Tat are directly neurotoxic. Virus and virally infected cells induces a chronic inflammatory process with nitric oxide, quinolinic and arachidonic acids. This cytokine production and the chronic inflammatory process cause indirect neurotoxicity. Mainly Categorised in 3 types : Asymptomatic neurocognitive impairment (ANI) Mild Neurocognitive Disorder (MND) HIV Associated Dementia (HAD)

13. HAD (2-8) - acquired impairment in at least two of the cognitive domains, measured as more than two standard deviations away from age-adjusted population norms and with marked impairment in activities of daily living. MND (20-30%) - acquired impairment in two or more of the cognitive domains by at least one standard deviation away from age-adjusted population norms, with some impairment in activities of daily living. ANI(30%) – same as MND but without any impairment in activities of daily living.

14. HIV-ASSOCIATED DEMENTIA : In the ICD -10 classification Dementia in human immunodeficiency virus disease is included under Organic mental disorder & prevalence is estimated at 15%. Autopsy studies of demented AIDS patients revealed characteristic white matter changes & demyelinization , microglial nodules, multinucleated giant cells, & perivascular infiltrates but a marked absence of HIV within neurons. Thus neuronal loss occurs through the action of macrophages & microglial cells &/or the through activation of cytokines & chemokines that trigger abnormal neuronal pruning. Typical late findings show an approximate 40% reduction in frontal and temporal neurons . Risk factors : Higher HIV RNA viral load Lower educational level Older age Anemia Illicit drug use Female sex

15. Clinically typical triad of symptoms —memory & psychomotor speed impairments, depressive symptoms & movement disorders . Apathy is a common early symptom. A frank depressive syndrome also commonly develops, typically with irritable mood & anhedonia instead of sadness & crying spells. Sleep disturbances are common. Restlessness & anxiety may be complicating factors. Psychosis develops in a significant number of patients, typically with paranoid ideas , although hallucinations are seen. Modified HIV Dementia Scale is a very useful bedside screen & can be administered serially to document disease progression.

16. On examination : Impaired saccadic eye movements Dysdiadochokinesia Hyper- reflexia . Frontal release signs (grasp, root, snout, & glabellar reflexes). In late stages, motor symptoms may be quite severe, with marked difficulty in smooth limb movements, especially in the lower extremities. Treatment : includes aggressive treatment with CART(COMBINED ANTIRETROVIRAL THERAPY) & treat associated symptoms aggressively. (Memantine, Selegiline) Depression-antidepressants Methylphenidate / other stimulants may be useful in the treatment of apathy.

17. Mild Neurocognitive Disorder (MND) Clinical Features :- Mild impairment in functioning Impaired attention or concentration Memory/concentration problems Low energy/slowed movements Impaired coordination Personality change, irritability or emotional lability Patient Complaints/Symptoms :- Patients may not recognize the problem since their is mild functional impairment Has difficulty with complex tasks Mild memory problems Distractibility/confusion Needs to make lists Adherence problems May make excuses for forgetting

18. Mild Neurocognitive Disorder (MND) The disorder is confirmed when mild impairments are present in at least 2 of the following domains : Verbal/language, attention, memory (recall / new learning), abstraction & motor skills. Prevalence data for MND are variable, often suggesting up to 60 % prevalence by late-stage AIDS. HAART may be of some benefit in slowing progression.

19. Major Depression in Patients with HIV Disease : 4-40 % HIV infected patients meet criteria for depressive disorder & a much higher % have depressive symptoms. Depression is a risk factor for HIV due to it’s impact on behaviour, intensification of substance abuse, exacerbation of self destructive acts & poor choice of partners in relations. Conversely HIV increases the chances of depression by direct injury to sub-cortical areas of brain, chronic stress, worsening social situation, demoralization etc. Some HIV related conditions can produce depression- (toxoplasmosis, cryptococcus, lymphoma) & patients with low testosterone levels / patients getting interferon alpha for co-morbid HCV treatment may have depression.

20. Treatment involves both antidepressant medications & psychotherapy. Pharmacotherapy – SSRIs > TCAs (better S/E profile) Fluoxetine and paroxetine TCAs - neuropathic pain. Bupropion - interactions with the ART drugs ritonavir and efavirenz Modafinil - reduced fatigue in HIV+ patients. EFAVIRENZ & INTERFERON – can cause depression or frank psychosis Psychological management: includes counselling, cognitive behaviour therapy supportive psychotherapy interpersonal psychotherapy .

21. SUICIDE IN HIV/AIDS : affect almost 30% of individuals at the time of testing & attempts tend to cluster in the first 6 months after a positive test result thus underlining importance of pre & post test counselling. Risk factors for attempts include social stigma, withdrawal of family support, loss of friends & partners, long term dependency & prospect of an incurable illness.

22. BIPOLAR ILLNESS IN PATIENTS WITH HIV DISEASE : Pts may have this condition after developing AIDS / already have pre-existing bipolarity prior to developing AIDS. A spectrum of symptoms from hypomanic features to frank mania may be encountered with elevated / irritable mood, decreased need for sleep, talkativeness, increased activity & even delusions & hallucinations. Some patients may have a delusion that they have discovered a cure for HIV & go into euphoria . AIDS Mania - seen in up to 8% of HIV-AIDS patients. a slightly different condition with onset in late stages of disease , lack of family history / past episodes & presence of cognitive impairment. Patients tend to have cognitive slowing / dementia. In AIDS Mania, irritable mood is more typical than euphoria & psychomotor slowing may be observed. This type of mania is usually more severe & has a chronic course with infrequent remissions & tends to relapse after cessation of therapy.

23. Treatment of classical mania early in AIDS is with mood stabilizers Eg :- lithium (cause delirium), valproate, carbamazepine ( cause BM suppression) , lamotrigine & antipsychotics (esp. SGAs). AIDS mania patients typically respond to treatment with antipsychotic agents alone. Late-stage patients are far more sensitive to the therapeutic effects but even more so to the toxic side effects of antipsychotic agents. In late-stage disease the dose of antipsychotic needed may be much lower than normally.

24. Schizophrenia in Patients with HIV Disease : Prevalence rates are b/w 4 & 19 % in both inpatient & outpatient samples. Schizophrenia contributes to behaviours that may lead to HIV infection. Patients with schizophrenia may have high rate of unprotected sex, multiple sex partners, trading sex for money & have sex while intoxicated. Patients with more positive symptoms & more impulsive behaviours may be prone to high risk sexual activities. Management employs antipsychotics for symptom control & psychological support & rehabilitation. Ritonavir has been shown to decrease plasma concentrations of olanzapine.

25. Personality in Patients Infected with HIV : Personality disorder prevalence among HIV infected is 19-36% & the most common is antisocial personality disorder which itself is a risk factor for HIV infection. Unstable extraverts are more prone to engage in HIV risk behaviour despite having knowledge of the consequences, for them the immediate removal of pain/ obtaining of pleasure assumes paramount importance. 2 ND most common (25%) type is the stable extravert .

26. Unstable introverts (14%) consist of the next most common group, who are anxious, moody & pessimistic; they seek drugs / sex not for pleasure but for relief from pain. Stable introvert (1%) they are controlled & even-tempered persons who are least likely to engage in risky behaviour. Personality factors may have significant implications for treatment like non adherence to medication regimes, engaging in high risk behaviours etc. & they have to be addressed during management of such patients. Personality traits were not directly related to HAART adherence. However, clinical experience suggests that non-adherence is more common among extroverted / unstable patients.

27. A cognitive-behavioural approach is most effective in treating patients. 5 Principles Guide Standard Care : Focus on thoughts, not feelings. Use a behavioural contract. Emphasize constructive rewards. Use relapse prevention techniques. Coordinate with medical care providers.

28. Worried Well : The so-called worried well are those high-risk groups who, although they are sero -negative & disease free, are anxious about contracting the virus. Some are reassured by repeated negative serum test results, but others cannot be reassured. Their worried well status can progress quickly to generalized anxiety disorder, panic attacks, obsessive compulsive disorder & hypochondriasis .

29. Substance Abuse & Addiction in HIV Disease : Substance abuse is a primary vector for the spread of HIV. This impact is directed not only at those who use intravenous drugs & their sexual partners but also at those who are disinhibited / cognitively impaired by intoxication & are driven by addiction to impulsive behaviours and unsafe sexual practices. Diagnosis of substance dependence may be difficult to make because physical symptoms of HIV infection overlap with those of substance abuse / dependence. Neurological symptoms can overlap b/w HIV infection & substance abuse. Double diagnosis refers to Substance abuse & Psychiatric illness. Triple diagnosis refers to a dual diagnosis patient who also has HIV. Most HIV-positive substance abusers would be classified as “unstable extroverts.” These can be found in as many as 49% of all substance abusers.

30. The clinician must be especially mindful of interactions b/w these medications & the abused substances. Eg :- ( Stavudine can cause neuropathy as a side effect which can be exacerbated by alcohol). Treatment of Substance Use Disorders in Patients Infected with HIV : 1. Role induction & motivation 2. Detoxification 3. Treatment of co-morbid conditions 4. Rehabilitation 5. Relapse prevention

31. Other Psychological Problems in Patients Infected with HIV : Acute stress reaction may be seen, most commonly at the time of learning a positive test result. Adjustment disorder may occur in 5-20 % of patients. Obsessive compulsive disorder may occur with / without depressed mood involving repeated bodily scrutiny for evidence of disease progression. Repeated ruminations may occur about death & dying & thoughts of having spread of the virus to others may be present. Other anxiety disorder like GAD, panic disorder may occur. HIV diagnosis can lead to PTSD in some patients. prevalence of PTSD is less than 1% and life time prevalence is 1 to 5% with female to male ratio is 2:1.

32. ART and it’s Psychiatric side effects Acyclovir – Visual hallucination, Confusion, Insomnia, Agitation Amphotericin B – Delirium Efavirenz – Disorientation, Confusion, Nightmares, Depression, Insomnia Ganciclovir – Mania, Delirium Interferon – Depression Lamivudine, Stavudine – Mania Zidovudine – Mania, Depression, Irritability, Insomnia, Headache

33. HIV-SPECIFIC PSYCHOTHERAPEUTIC ISSUES : 1)Pretest , test & posttest counseling issues; 2) Risk behaviour reduction in patients at risk / infected with HIV; 3) Partner notification in patients infected with HIV; 4)Impaired patients with issues of capacity & competence; 5)HAART adherence issues.

34. Pre test counselling

35. Post test HIV Counselling meaning of test results, recommendations for treatment, and risk reduction interventions to stem the spread of HIV infection. should occur in both HIV- negative and HIV-positive patients. psychological reactions including suicidal feelings, anger, homicidal thoughts directed at potentially infecting partners, overwhelming grief, and complete psychological breakdown. Patients with poor coping skills, poor impulse control, history of suicidal faeelings and behaviors, substance abuse disorders, and lack of social supports – spl . Attention!

36. RISK BEHAVIOR REDUCTION IN PATIENTS AT RISK / INFECTED WITH HIV Interventions include: Stress management & relaxation techniques Education Cognitive self-management training Negotiation skills training Psychotherapy directed at emotional distress reduction Relapse prevention models for high-risk behaviour reduction Education directed at eroticizing safer sex Assertiveness training Peer education in bars

37. PARTNER NOTIFICATION Partners should be notified of exposure risk & potential infection as well. Physicians / health department officials to notify partners of HIV-infected patients of their risk. Sex workers & their clients can make their own decisions & should be responsible for their own behaviour all the way to the sentiment that HIV infected sex workers should be arrested & jailed for attempted murder.

38. CAPACITY TO CONSENT/COMPETENCE : Patient must understand that there is a decision before him / her regarding some aspect of care & must understand the consequences not only of each option but also of refusal to make a choice. The patient must be able to manipulate the information involved in a rational way. Patterns of prior behaviour, severity of illness, poor judgment, & psychiatric vulnerabilities complicate these decisions & play an important role in tempering the way in which patients are managed.

39. HAART ADHERENCE Intervention such as cognitive-behavioural psychotherapy, structured psycho-educational psychotherapy, supportive psychotherapy, & group interventions have all been used to improve patient adherence to office visits & medication regimens. HIV medication adherence focuses on technical interventions such as pill box & timer reminders, less complex pharmacological interventions, decreased pill burdens, & increased access to care. Psychotherapy has been shown to improve clinic visit adherence, the best indirect predictor of medication adherence.

40. References : CTP-10 th Edition Volume 1. Lishman’s Organic Psychiatry 4 th Edition. H arrison’s Principles of Internal Medicine 19 th Edition Volume 2.

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