HIV and Brain Func.on. Tristan J Barber Research Physician St Stephen s AIDS Trust Chelsea and Westminster Hospital

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1 HIV and Brain Func.on Tristan J Barber Research Physician St Stephen s AIDS Trust Chelsea and Westminster Hospital

2 HIV and the Brain When can HIV affect the brain? Seroconversion Long term infected (not on treatment) HIV vs. AIDS Long term infected (on treatment) Old age What can be measured, or not? How do we diagnose it?

3 Prac.cal aspects the history Nature of the onset Time course Type of memory failure If the history suggests that the cogni.ve problems are limited to memory alone, think of non HIV related causes of memory loss e.g. Alzheimer s Memory loss in the context of other cogni.ve changes increases suspicion of HAND aten.onal difficul.es psychomotor retarda.on execu.ve problems (difficulty with high level cogni.ve processing, such as planning, problem solving, and mul. tasking)

4 Important other considera.ons Other causes (may also present with slowly progressive cogni.ve changes) Sleep apnoea vitamin B12 deficiency thyroid disorders Acute onset memory changes are more o[en associated with strokes or infec.ons (herpes simplex encephali.s) Deficits of aten.on can occur in a number of se\ngs sleep depriva.on excessive stress fa.gue chronic pain medica.on side effects

5 HAND Triad of cogni.ve, motor and behavioural dysfunc.ons Memory Poor concentra.on, reading difficul.es Delayed speech with long pauses between words Poor thought, lack of emo.onal content and spontaneity Social withdrawal?depression Gait abnormali.es Frontal release signs, spas.city and brisk deep tendon reflexes

6 HAND Differen.al Diagnosis Psychiatric history common Substance abuse or withdrawal may mimic HAND Co infec.on with HCV and/or its treatment Combina.on of tests to exclude other causes Neuropsychological evalua.on Neuroimaging CSF

7 Older popula.on The prevalence of neurocogni.ve disorders among middle aged and older persons with HIV infec.on in the HAART era has not been well characterized Older HIV posi.ve persons have been found to have a higher prevalence of symptoms related to depression, alcohol abuse, and drug abuse than agematched HIV nega.ve controls, and these factors would probably influence the prevalence of neurocogni.ve problems

8 Modified from Ellis et al, Nat Rev Neurosci 2007 and Grant et al., CROI 2009 HAD HIV associated demen.a MND HIV associated mild neuro cogni.ve disorder ANI asymptoma.c neurocogni.ve impairment

9 Damaged brain may heal poorly Legacy of prior damage Nadir CD4 count CHARTER analysis suggest significant impact of nadir <350 Data too limited to test higher nadirs Implies earlier treatment could be helpful CROI 2010, Poster 429, Ellis, et al

10 Viral Load Plasma viral load is the strongest correlate of CSF viral load, emphasizing the importance of systemic HIV suppression for control of HIV in the nervous system Without ART, higher CSF VLs also correlated with older age and more advanced current and past immunosuppression With ART, detectable CSF VLs were associated with worse adherence, worse es.mated an.retroviral penetra.on, and non white ethnicity The mechanisms by which age and ethnicity influence CSF VL are unknown Among people not taking ART, worse global neurocogni.ve performance was associated with having CSF VLs that were at least as high as plasma VLs

11 Prac.cal Trailmaking Can t show or do prac.cally as may cause learning effect

12 Anxiety and Depression

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15 Conclusions Most important diagnose neurocogni.ve decline (HAND and other HIV related issues) vs. other problems that may present with similar features Not certain if it is all about ART and CNS penetra.on further studies needed Aspects of mood, diet, physical ac.vity, independence, adherence are most important issues

16 BHIVA Recent Data 101 patients on stable antiretroviral therapy without any obvious neurological symptoms or other illnesses All had HIV for more than six months. Two types of test 20-minute computerised cognitive assessment test Cogstate and the International HIV Dementia Scale (IHDS) Neurocognitive impairment was defined as scores more than one standard deviation below the mean acompared to age-matched population data in at least two areas of functioning

17 BHIVA Recent Data Median age 53 Majority (77%) white men HIV-positive for an average of 14 years Mean CD4 count of 559 and lowest-ever CD4 count (nadir) of 185 A high proportion 25% - had hepatitis C Overall rate of neurocognitive impairment was 19%, only 3% above general population Fine muscular movement, multitasking and executive function (prioritising and planning) were particularly impaired CD4 nadir was associated with a high IHDS score