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Neurocognitive Impairment, Symptomatic Peripheral Neuropathy and Depression are Highly Prevalent in

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... Gavin McCormack, Margaret Hellard, Kate Cherry, Justin McArthur and ... 658 HIV outpatients and 161 HIV- controls enrolled. 10 sites across 8 countries ... – PowerPoint PPT presentation

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Title: Neurocognitive Impairment, Symptomatic Peripheral Neuropathy and Depression are Highly Prevalent in


1
Neurocognitive Impairment, Symptomatic Peripheral
Neuropathy and Depression are Highly Prevalent in
HIV infected Outpatients within the Asia Pacific
Region Findings of the Asia Pacific NeuroAIDS
Consortium (APNAC) Study
Edwina Wright, Bruce Brew, Arkhom Arayawichanont,
Kevin Robertson, Kanoksri Samintharapanya,
Subsai Kongsaengdao, Megan Lim, Saphonn
Vonthanak, Luxshimi Lal, Chel Sarim, Sarah
Huffam, Patrick Li, Darma Imran, Jenny Lewis, Wen
Hui Lun, Adeeba Kamarulzaman, Goa Tau,
Sophaginine Ty Ali, Kamal Kishore, Margaret Bain,
Rosamond Dwyer, Gavin McCormack, Margaret
Hellard, Kate Cherry, Justin McArthur and
Steve Wesselingh on behalf of the APNAC
Study Team
2
The Asia-Pacific NeuroAIDS Consortium
  • Formed 2002
  • PNG
  • Cambodia
  • India
  • Fiji
  • Indonesia
  • Thailand
  • Hong Kong
  • Singapore
  • Malaysia
  • China
  • Australia

UNAIDS 2003
3
Prevalence HIV Neurological Disease in
Asia Pacific Region
3 million people in Asia Pacific Region have
advanced, largely untreated HIV disease 2,3
  • In western countries
  • ? 1/3 of patients with advanced, untreated HIV
    disease develop neurological disorders 4
  • Thus ? 1 million people at risk of HIV-related
    neurological disease in AP Region

8.3 million HIV people live in the Asia
Pacific Region1
www.thebody.com/
1. UNAIDS/WHO, AIDS Epidemic Update Dec 2005 2.
Zhou et al, J Acquir Immune Defic Syndr 2005. 3.
UNAIDS/WHO, Progress on Global Access to
Antiretroviral therapy. An update on 3X5, Dec
2005. 4. Snider et al Ann Neurol 1983
4
Exact Prevalence Estimates
1. Nakagawa et al, Int Med 1997 2. Oh et al, CID
1999 3. Satischandra et al, Indian J Med Res
2000 4. Portegies et al, AIDS 1993 5. McArthur
et al, Neurol 1993 6. Sacktor et al, J
Neurovirol 2002 7. Cysique et al, Arch Neurol
2004 8. Schiffito et al, Neurol 2002
5
The APNAC Study Aims
  • To determine the prevalence of
  • HIV-related Neurocognitive Impairment (NCI)
  • Symptomatic Peripheral neuropathy (SN)
  • In HIV infected outpatients across the Asia
    Pacific Region

6
APNAC Study Methods
  • Cross-sectional study at 10 sentinel outpatient
    sites in 8 APNAC countries
  • Standardised training at all sites
  • Enrolled HIV outpatients and HIV negative
    controls for 2-3 week periods

7
APNAC Study Tools
  • Neurocognitive Function
  • Neuropsychological test battery1
  • Timed gait
  • Grooved pegboard
  • Finger tapper
  • Semantic fluency
  • Depression screening tool CES-D2,3,4
  • Alcohol and substance use questionnaire5,6
  • Symptomatic Peripheral Neuropathy
  • ACTG Peripheral Neuropathy Screening Tool7

1. Price et al, AIDS 1999 2. Radloff, Appl
Psychol Meas 1977 3. Cockram et al, Aust NZ J
Med 1999 4. Mackinnon et al, J Gerontol B
Psychol Sci Soc Sci 1998 5.NHMRC Australian
Alcohol Guidelines, 2001 6. NIAAA. US Dept
Health Human Services 2005 ed. 7. Cherry et al,
Neurol 2005.
8
Study Definitions
  • Neurocognitive Impairment
  • Patients were defined as impaired if they scored
    2SDs below the mean scores obtained from local
    HIV negative controls on two of the four
    neuropsychological tests1,2,3
  • This degree of NCI plus evidence of major
    functional decline plus no intercurrent condition
    HIV Associated Dementia
  • This degree of NCI alone moderate-severe
    neurocognitive impairment
  • Depression
  • A score gt16 on CES-D screening tool4,5,6

1. Grunseit et al, J Clin Exp Neuropyschol 1994
2. Cysique et al, J Neurovirol 2004 3. Woods et
al, Clin Exp Neuropyschol 2004 4. Radloff,
Appl Psychol Meas 1977 5. Cockram et al, Aust NZ
J Med 1999 Mackinnon et al, J Gerontol B
Psychol Sci Soc Sci 1998.
9
Study Definitions
  • Symptomatic Peripheral Neuropathy
  • Definite
  • Symptoms plus absent ankle reflexes plus
    vibration sense at great toes ?10 seconds
  • Probable
  • Symptoms plus EITHER absent ankle reflexes OR
    vibration sense at great toes ?10 seconds

10
Results
  • July 2005 - March 2006
  • 658 HIV outpatients and 161 HIV- controls
    enrolled
  • 10 sites across 8 countries
  • 80 ARVs and 65 HAART

11
APNAC Study Sites
www.lib.utexas.edu
12
Results Demography
P-value lt 0.05 significant
13
Results Demography
14
Results
  • Neurocognitive Impairment 12
  • 76/647 patients
  • 35 of patients not receiving HAART
  • Depression 36
  • 235/645 patients
  • Few patients on antidepressants
  • Symptomatic Sensory Neuropathy 19
  • 126/640 patients
  • Definite (6) and Probable (13)
  • 63 patients had prior or current use d-drugs1
  • 26 patients were receiving pain relief

1. d-drugs stavudine, didanosine or zalcitabine
15
Risk Factors for NCI, Depression and SN
1. Univariate analysis Agegt35 years 2.
Univariate analysis CD4 nadir (mean)gt 80
cells/uL 3. Diabetes defined as diagnosis of
diabetes or use of diabetic drugs numbers too
small to be included in univariate analysis.
significance p value lt 0.05
16
Risk Factors for NCI, Depression and SN
17
Discussion
  • First study within the Asia Pacific Region to
    report the likely burden of
  • HIV-related Neurocognitive Impairment
  • Symptomatic Sensory Neuropathy
  • Depression
  • Broad relevance of these findings to the AP
    Region
  • Up to 1.0 million people may have HIV associated
    dementia
  • 1.5 million people may have symptomatic sensory
    neuropathy
  • Over 1/3 HIV infected patients may have depression

18
Discussion
  • Further relevance findings
  • NCI, Depression and SN under-diagnosed
  • NCI and depression gt Poor adherence1,2
  • NCIgtIncreased risk job loss3
  • Alternative treatment options required
  • Evidence-based treatment strategies required for
    Asia Pacific region

1. Hinkin et al, Nat Med 2002 2. Yun et al, J
Acquir Immune Defic Syndr 2005 3. Albert et al,
Arch Neurol 1995
19
Summary
  • HIV-related neurocognitive impairment, depression
    and symptomatic peripheral neuropathy are highly
    prevalent in the Asia Pacific Region
  • These findings have implications regarding
    treatment options and the need for further
    research to inform current and future treatment
    strategies

20
APNAC Study Team
Dept Medicine, Sappasithiprasong Hospital,
Ubonratchathani, Thailand Arkhom
Arayawichanont Dept Neurology, University North
Carolina, NC USA Kevin Robertson Dept Internal
Medicine, Division of Neurology, Lumpang
Hospital, Muang District, Thailand Kanoksri
Samintarapanya, Panita Pathipvanich Division of
Neurology, Dept Medicine, Rajavithi Hospital
Bangkok, Thailand Subsai Kongsaengdao National
Centre HIV/AIDS, STD and Dermatology Social
Health Clinic, Phnom Penh Cambodia
Saphonn Vonthanak, Chel
Sarim, Sarah Huffam


Queen
Elizabeth Hospital, Hong Kong Patrick Li, Iris
Chen Dr Cipto Mangunkusomo Hospital, Jakarta,
Indonesia Darma Imran, Jofizal Jannis
Beijing Ditan Hospital, Beijing, China Wen Hui
Lun, Guang Zeng, Key Xu University Malaya
Medical Center, Kuala Lumpur, Malaysia Adeeba
Kamarulzaman, Clarence Sim Port Moresby General
Hospital, Port Moresby PNG Goa Tau Reproductive
Health Clinic and Colonial War Memorial Hospital,
Suva Fiji Sophaginine Ty Ali, Kamal Kishore Dept
Neurology, The Johns Hopkins Hospital, Baltimore,
USA Justin McArthur, Sandy Zhang St Vincents
Hospital, Sydney, Australia Bruce Brew, Margaret
Peggy Bain Burnet Institute, Melbourne, Australia
Steve Wesselingh, Luxshimi Lal, Megan Lim, Jenny
Lewis, Darshini Devadson, Margaret Hellard, Gavin
McCormack The Alfred Hospital, Melbourne,
Australia Rosamond Dwyer, Craig Scholten, Teresa
Girke, Jenny Hoy, Sharon Lewin, Edwina Wright

Study funded by NINDS and NIMH, NIH
21
Study Definitions Depression, Substance and
Alcohol Use
  • Significant risk of underlying depression
  • Score gt 16 on CESD-20 Screening tool
  • Excess alcohol intake
  • More than 4 standard drinks on 4-7 days per week
    in preceding 6 months
  • Significant substance use
  • Use of amphetamines, heroin, ketamine, LSD,
    marijuana, MDMA, methamphetamine, PCP, crack
    cocaine in the preceding 6 months

22
Study Numbers
23
Statistical Methods
  • Controls
  • Student t-test and chi-square
  • Univariate analysis
  • Chi-square test and Fishers exact test
  • Current CD4 cells lt 200/uL, Nadir CD4 cell count,
    Prior ADI, Prior CNS AIDS illness, Prior head
    injury, Education level less than high school,
    CES-D score gt16, Use of pain medication, Use of
    ARVs (none, lt3, gt3), Use of neuroHAART,
    Hepatitis C antibody positivity, Diagnosis of SN,
    Diagnosis of NCI
  • Multivariate analysis
  • Logistic regression

24
PN screening in APNAC study
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