1. Lesson 2: Neurocognitive Disorders and Mental Illness
Core Competency 5: Subpopulations of HIV/HCV Co-infected Persons
Lesson 2: Neurocognitive Disorders and Mental Illness
July 2017

2. Authors and Funders
This presentation was prepared by Francine Cournos, MD, (Northeast/Caribbean AETC) for the AETC National Coordinating Resource Center in July 2017.
This presentation is part of a curriculum developed by the AETC Program for the project: Jurisdictional Approach to Curing Hepatitis C among HIV/HCV Co- infected People of Color (HRSA ), funded by the Secretary's Minority AIDS Initiative through the Health Resources and Services Administration HIV/AIDS Bureau.

3. Lesson Objectives
Understand how neurocognitive impairment, substance use disorders, other mental disorders (especially depression) affect the care continuum for HIV mono-infection and HIV/HCV co-infection
Select screening instruments for diagnosing common mental disorders (including substance use disorders) most applicable to this population
Cite resources for the management and treatment of substance use and other mental disorders most relevant to this population
Discuss patient engagement in mental health care

4. Neurocognitive Disorders and Mental Illness May Manifest:
Due to HCV infection alone
Due to HIV infection alone
Due to co-infection with HCV and HIV
Neurocognitive disorders and mental illness can result from 1) HCV infection alone; 2) HIV infection alone or; 3) coinfection of HIV and HCV.

5. Cognitive Impairment in HCV Infection1,2
Chronic HCV infection is associated with:
Impaired attention
Psychomotor slowing
Impaired working memory
Impaired executive function
Chronic HCV infection is also associated with an increased risk for dementia

6. Cognitive Impairment in HCV Infection
Potential Causes:
Direct HCV effects on the brain
Severity of liver disease, including hepatic encephalopathy
Alcohol and substance use—both past and present
Depression and other mental illnesses
INF treatment—infrequently used now

7. HIV-Associated Neurocognitive Disorders (HAND)3
Specific Disorder
Neuropsychological Testing
Function
Mild Neurocognitive Impairment (MND)
Mild-moderately impaired in at least two cognitive domains
Typically mild to moderate impairment
HIV-associated Dementia (HAD)
More severely impaired in at least two cognitive domains
Typically more severe impairment
Asymptomatic Neurocognitive Impairment (ANI)
Any degree of impairment in at least two cognitive domains
No identified impairment
Cognitive Impairment in HIV Infection:
Is better studied than cognitive impairment in HCV mono-infection or HIV/HCV co-infection
Has well-defined criteria for specific neurocognitive disorders, although these criteria are based on neuropsychological testing which is often not available
Overlaps with cognitive impairment seen in HCV infection, especially in the areas of attention, working memory and executive function

8. Neuropsychological Impairment in the Era of Effective ART4
HIV infection without cognitive impairment
Asymptomatic Neurocognitive Impairment
Mild Neurocognitive Disorder
HIV-Associated Dementia
CHARTER Study (n=1,555 HIV-infected adults)
52% had NP impairment: HAD 2%, MND 12%, ANI 33%
Figure modified from Li, 8 8

9. Clinical Features of Impairment due to HAND5
Cognition
Memory loss
Concentration
Mental slowing
Comprehension
Behavior
Apathy
Depression
Agitation, Mania
Slide from Valcour; Atlanta 2013
Motor
Unsteady gait
Poor coordination
Tremor
Valcour, 2013

10. Impact and Consequences of HAND
Poorer survival6,7
Diminished self-care ability and quality of life8
Deterioration in work performance, higher unemployment rate9
Suboptimal drug adherence10,11
Impaired driving, increased accident risk12
Significant personal, economic and societal burden
Slide modified from Li, 10

11. Problems with Recognition of HAND13
The vast majority of patients with HAND have mild or no symptoms
Patients may not volunteer symptoms from lack of awareness or insight
Clinicians caring for people with HIV infection may not have relevant training for diagnosing HAND
Practical difficulties with routine screening for HAND in busy clinic settings
Limited access to formal neuropsychological testing
Slide modified from Li,

12. Management of HAND13 Exclude and manage reversible causes
Optimize of ART regimen:
Complete HIV VL suppression in blood and CSF
Genotypic resistance testing
Consider possibility of ARV toxicity
Adjunctive therapy has only small benefits (primarily methylphenidate for attention problems)
Medication adherence management
Cognitive rehabilitation
Support for activities of daily living
Slide modified from Li,

13. Cognitive Impairment in HIV/HCV Co-infection
People with HIV/HCV co-infection14
Were more likely to have impairments in global deficit score than people with HIV mono-infection
Had significantly poorer information processing speed than people with HIV mono-infection
Did not differ in cognitive domains from people with HCV mono-infection15
There are a limited number of studies that compare cognitive problems seen in people with HIV/HCV co-infection to cognitive problems seen in people with either HIV or HCV mono-infection or to controls
14. Fialho et al, AIDS Care, Review of these limited studies in 2016.
15. Clifford et al, Neurology, This study suggests that liver damage may play a significant role in those studies that find people with HIV/HCV co-infection have greater cognitive impairment than those with HIV mono-infection.

14. Management and Treatment of Cognitive Impairment in HIV/HCV Co-infection
The primary approach is to establish and maintain undetectable HIV VL and HCV SVR
Early treatment helps to preserve cognitive functioning
Co-morbid disorders that impair cognition also need attention

15. Mental Disorders and PWID
Multiple studies of PWID demonstrate:
Nearly universal opioid dependence
Dependence on multiple other non-opioid substances (including alcohol) exceeding 50%
Elevated rates of mood and personality disorders
Reference documents at

16. Common Mental Disorders among PLWH
Depressive disorders
Anxiety disorders
Alcohol/Substance use disorders
Psychotic illnesses and bipolar disorder
Stress disorders, including PTSD
Somatic problems: insomnia, pain, fatigue, sexual dysfunction
Reference documents at

17. Depression in PLWH Is Associated with:
Increased morbidity and mortality
women living with HIV and chronic depression are twice as likely to die
Failure to initiate ART
Failure to adhere to ART once initiated
Slower virologic suppression
Higher rates of sexual risk behavior
Reference documents at

18. Alcohol/Substance Use in PLWH Is Associated with:
Failure to initiate ART treatment
Failure to adhere to ART once initiated
Faster virologic failure
Higher rates of sexual risk behavior
Increased mortality
Reference documents at

19. Mental Disorders Are Co-morbidities of HIV/HCV Co-infection
HIV infection, HCV infection, and mental disorders are syndemic
People with mental disorders have elevated rates of both HIV and HCV infection compared to the general population
PLWH and/or HCV infection have higher rates of mental disorders than the general population

20. Depression

21. Depression Is a Common Co-morbidity of HIV Infection17
Present in about 30%-50% of PLWH in HIV care and treatment settings
Rates vary by study design (e.g., population, severity threshold, measurement tools); and range from 0%-80%
Major depression is as much a physical illness as it is a mental illness.
AFFECTIVE
Depressed mood
Loss of interest
Guilt, worthlessness
Hopelessness
Suicidal ideation
SOMATIC
Appetite/Weight loss
Sleep disturbance
Agitation/retardation
Fatigue
Loss of concentration

22. Screening for Depression: PHQ-221
Over the last two weeks how often have you been bothered by any of the following problems:
2. Feeling down, depressed or hopeless
0=Not at all
1=Several days
2=More than half the days
3=Nearly every day
1. Little interest or pleasure in doing things.
0=Not at all
1=Several days
2=More than half the days
3=Nearly every day
The Patient Health Questionnaire – 2 is a validated diagnostic instrument for depression with 2 questions.
Online Version:
National HIV Curriculum:
Downloadable and in Spanish:
Depression Screening Tools:
If the score is 3 or more, major depression is likely; continue screening with the PHQ-9.

23. PHQ-9
The Patient Health Questionnaire – 9 is a validated diagnostic instrument for depression with 9 questions.
Online Version:
National HIV Curriculum:
Downloadable and in Spanish:
Depression Screening Tools:

24. Assessment for Depression
Evaluate for contributing biological factors, for example prescribed medications, alcohol and other substances, hypothyroidism, hypogonadism, etc.
Try to rule out bipolar disorder
Ask: Past history or family history of mania?
Ask: In the past year, while not high or intoxicated, did you ever feel extremely energetic or irritable and more talkative than usual?

25. Antidepressants: Limited Studies in HIV Treatment
In general, SSRIs are well tolerated, safe, and have lower rates of drug discontinuation in studies with PLWH – all have equal efficacy
SSRIs are the most studied
Check for drug-drug interactions
SSRIs have proven efficacy in clinical trials with depressed patients living with HIV
Drug interactions need to be considered with fluoxetine and paroxetine
Avoid paroxetine in pregnancy (category D)

26. Psychotherapy for Depression
Effective psychotherapies (eg, CBT, IPT) for mild-moderate depression and/or to augment antidepressant medication in moderate-severe depression
May not be available in HIV primary care setting
Factors contributing to limited availability
Cost of training providers and number of providers
Poor reimbursement for therapy
Poor dissemination of research-based approaches
Lack of priority

27. Alcohol/Substance Use and HIV

28. Screening, Brief Intervention and Referral to Treatment (SBIRT)
SBIRT is an evidence-based practice used to identify, reduce, and prevent problematic use, abuse, and dependence on alcohol and illicit drugs
SBIRT lends itself to use in primary/HIV/HCV care
SAMHSA-HRSA Center for Integrated Health Solutions:
Other screening tools
Audit-C Questionnaire22
DAST 10
National HIV Curriculum:

29. Buprenorphine for Opioid Use Disorders24
Buprenorphine treatment integrated into medical care for HIV, HCV, and HIV/HCV co-infection can improve adherence to treatment among people with opioid use disorders
Opioid substitution treatment is significantly associated with a lower risk of HCV reinfection following successful HCV treatment

30. Tobacco Addiction

31. Impact of Tobacco Use among PLWH25
A study of tobacco smoking was conducted from in Denmark where HIV care and treatment is free
2,921 PLWH age 35 or over were followed for 14,281 person years and compared to controls
The number of life-years lost in association with HIV was 5.1
The number of life-years lost in association with HIV and smoking combined was 12.3

32. Study Results: Survival by Age, HIV, and Smoking Status25
Kaplan-Meier curve showing survival by age, stratified by human immunodeficiency virus and smoking status for all study subjects. People who smoke are represented by the lowest line on the graph and have a dramatically reduced life span when compared to people who are HIV negative and don’t smoke (top line), people who are HIV negative and smoke (this shortens life span by four years), people who are HIV positive and don’t smoke (this shortens life span by five years), and people who are both HIV positive and smoke (this shortens lifespan by 12 years, showing a synergistic effect).
Helleberg, 2014

33. Smoking and Mental Illness26
Rates of smoking by type of mental disorder:
No mental disorder: 21 %
Any anxiety disorder: 38 %
Any mood disorder: 45 %
Any substance use disorder: 64 %
Tobacco addiction is a substance use disorder that is comorbid with other mental illnesses.
U.S. National Comorbidity Survey-Replication,

34. Smoking and Mental Disorders
Almost half of all cigarettes in the U.S. are consumed by people with mental disorder(s)
Bupropion and varenicline increase smoking abstinence rates in smokers with mental disorders, and studies suggest they are safe to use in this population

35. Post Traumatic Stress Disorder (PTSD)

36. Primary Care PTSD Screening Tool (PC-PTSD-5)
Examples given for such an event(s) on the screener are as follows:
a serious accident or fire
a physical or sexual assault or abuse
an earthquake or flood
a war
seeing someone be killed or seriously injured
having a loved one die through homicide or suicide
Primary Care PTSD Screen for DSM-5 (PC-PTSD-5)
Online tool:
Downloadable PDF:

37. PTSD Prevalence 8% of adult U.S. population; 12% in women
Highest rates found with interpersonal violence:
Survivors of rape (especially when under 16 years)
Military combat and captivity
Genocide
Studies of rates of PTSD among PLWH vary from 5% - 74%
Varies with the population studied
Women in care for HIV in the U.S. have a rate of PTSD of about 30%

38. PTSD in Response to an HIV Diagnosis27
PTSD may occur after a person receives an HIV diagnosis, but:
The HIV diagnosis is usually not the exclusive reason
This tends to occur in the context of an already traumatic life

39. Impact of PTSD on Course of HIV Disease28
There are few studies
The common PTSD co-morbidities of depression and alcohol/substance use disorders are associated with worse HIV outcomes and should be treated
PTSD is associated with more unexplainable pain and more HIV physical symptoms
Patients with PTSD often have trust problems. Meet the patient where s/he is and work from there to meet mutually agreed upon goals. Show continued interest and concern.

40. Care Components for Neurocognitive and Mental Disorders
Screen
Confirm diagnosis
Link to care
Retain in care
Provide successful treatment
Just as with HIV, HCV and HIV/HCV co-infection, the treatment of neurocognitive disorders and mental illnesses have their own cascades. Screening with effective follow-up does not produce successful outcomes.

41. Provider Attitudes that Make the Therapeutic Alliance More Difficult
I know best what the patient needs
It’s my role to advise the patient and to get them to follow that advice
The patient is treatment resistant
The patient is manipulative
The patient doesn’t want help
The patient refuses my help, so I’m not responsible
The patient doesn’t deserve help

42. Provider Attitudes that Enhance the Therapeutic Alliance
“We’re in this together” (us versus your problems)
“What do YOU want help with?”
“I care about your opinion of my recommendations”
“It's okay for us to disagree”
People should be allowed (and encouraged) to take control over their own lives
People do things to feel better
Patients’ perception of their reality is critical

43. Disclaimer and Permissions
Users are cautioned that because of the rapidly changing medical field, information could become out of date quickly.
You may use or present this slide set and other material in its entirely or incorporate into another presentation if you credit the author and/or source of the materials.
The complete HIV/HCV Co-infection: An AETC National Curriculum is available at:

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