HIV through the Life Cycle

Dr. Adriana Carvalhal, MD, MSc, PhD Assistant Professor - Department of Psychiatry Director Consultation-Liaison Psychiatry – St. Michael‘s Hospital

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The Good News: The impact of HAART

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HIV and the ageing population •  By 2015, nearly 50% of persons living with HIV/AIDS will be >50 years1

•  The number of persons >65 years of age at AIDS diagnosis has grown 10-fold in the last 10 years2

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1. Centers for Disease Control and Prevention. Cases of HIV and AIDS in the United States and Dependent Areas. HIV/AIDS Surveillance Report 2005. Available at

http://www.cdc.gov/hiv/topics/surveillance/resources/reports/2005report/pdf/2005SurveillanceReport.pdf 2. Stoff DM, et al. AIDS 2004;18(suppl 1):S1–S2

Smith C. 16th CROI, 2009, Abstract 145

Causes of death in the D:A:D study

•  This study reiterates the importance of addressing traditional, non-HIV specific risk factors in order to further reduce death rates in HIV positive populations

•  An international observational study of HIV-infected individuals This analysis included:

•  33,347 patients •  2.192 deaths over 158,959 person-year •  13.8 deaths per 1,000 person-years (95% CI: 13.2–14.4)

AIDS-related 32%

Liver-related 14%

CVD-related 11%

Non-natural 9%

Bacterial infection 7%

Lactic Acidosis / Pancreatitis 1%

Renal 1%

Other unknown 13%

Non-AIDS cancers 12%

Peter

•  56 year old man, single, living alone

•  Until recently worked as an investor on Bay street (partner in the company)

•  Over the last 2-3 years progressively with memory problems

•  Coping with several practical strategies and delegating a lot to other (“Not my style!”)

•  Last year made a huge mistake at work and decided to leave the firm

•  “Not sure what to do with my life!”

Peter

•  Short-term memory

•  Difficulties with concentration

•  Difficulties with “multi-task”

•  “I’m not so sharp any more!”

•  “Everything takes longer!”

•  Difficulties to adapt to a different life style

•  Feels lonely - crystal meth

•  Social withdrawal

•  Not enjoying things in the same way – plans for future

Common Mental Health Problems in PHAs

!   Depression !   Substance Use Disorder (SUD) !   HIV-Associated Neurocognitive Disorder (HAND) !   Other conditions can affect mental health:

!   Lipodystrophy !   Social determinants of health !   Side effects from ARVs

Neurocognitive Changes in HIV

HIV-related: !  CNS Lymphoma

!  HAND

Non-HIV related:

!  Aging

!  Depression

!  Substance Use

!  HCV Co-infection

!  Dementia:

!  Alzheimer s

!  Cerebrovascular disease

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BACKGROUND

HAART Era: Dementia Prevalence Decreased, Milder HAND Persists

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Inhibition of grown factor production!

Glutamate levels!

Neuronal Stress

Neuronal Death

Gliosis

HIV: Potential Mechanisms of Brain Injury

Adapt Avison et al, 2002!

CNS: distinct virologic compartment for HIV

Methods

•  Paired CSF and plasma samples collected from HIV-infected patients ARV-naive with middle cognitive impairment

•  NPZ-6 (baseline and 6 months): Logical memory, verbal fluency, word span, visual recognition, Stroop test

•  Treatment with AZT + 3TC + EFZ

Results

•  Differences in response in plasma and CSF viral load

•  70 % of patients with undetectable viral load in 6 months

•  Undetectable CSF viral load was not significantly associated with improvements in cognitive performance

Conclusion

•  Data support hypothesis: CSF and plasma represent virologically distinct biological compartments

•  Limitations: ARV treatment, number of patients, need for longer FU

Carvalhal A et al, 2006 Infection 34(6):357-60!

Definition of HAND(

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Pre-existing cause

Delirium absent

Acquired impairment

in ! 2 cognitive abilities

Interferes with daily

functioning

Asymptomatic neurocognitive impairment (ANI)

No Yes Mild No

Mild neurocognitive disorder (MND)

No Yes Mild Mild

HIV-associated dementia (HAD)

No Yes Marked Marked

HAND: Prevalence

CHARTER 1 ALLRT2 Neuradapt3 OCS4

Prevalence of neurocognitive deficit

51% 39% 23% 59%

N (% men) 1562 (74%) 1160 (87%) 158 (79%) 834 (73%)

Mean age, years 43 41 44 47

ARV 83% 100% 86% 100%

Undetectable VL 40% 70% 54% 92%

Current CD4/ mm3 461 424 558 530

Nadir CD4 NA 213 NA 57% <200

HCV co-infection 26% NA 22% 11%

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Pathophysiology and Risk Factors !%(T#JT),&#'#@&M+*%M(#",+

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Improvement with ARV

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Functional MRI shows that brains of patients infected

with HIV look 15-20 years older than brains without HIV

Cerebral blood flow

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HIV + Aging !  Cause frailty phenotype(C

!  decreased physical function and ability to maintain homeostasis

!  vulnerability to immunological stressors

!   inflammatory dysregulation

!  Age = 50(E

1. Ances et al 2010. JID 201: 336-340!2. Desquilbet L et al 2009 JAIDS; 50: 299-306!

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Dementia - Vascular !  Hypertension 2('. common comorbitidy

!  HIV+ higher risk for cerebrovascular disease !  aging

!  direct impact of HIV infection

!  SE from ARVs: mainly dyslipidemic effect of PIs

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Supportive measures

What happen with Peter ?

•  Neuropsych testing: MND

•  Plasma VL: undetectable

•  MRI: middle cortical atrophy

•  CSF VL: undetectable

•  Rehabilitation: “Brain Fitness Program”

•  Support and mindfulness therapy

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