Two studies presented at the17th British HIV Association (BHIVA) conference last week suggest that the proportion of people who have subtle brain impairment due to HIV may not be as high as previously thought, and may in fact be little higher than in the general population.
Several studies measuring neurocognitive impairment (deficits in memory, thinking and movement) in people with HIV in the last few years have concluded that a high proportion of people with HIV have subtle impairments. These may not cause symptoms that interfere with daily life, but can be detected by psychological tests.
About 16% of the general population has some degree of neurocognitive deficit. It therefore caused a lot of concern when in 2010 the large CHARTER trial in the USA found that 52% of 1526 people with HIV had evidence of neurocognitive impairment.
A quarter of these people had other conditions that were probably the major cause of their brain impairment, but that still meant that 39% of all HIV-positive patients had brain impairment without any other obvious cause, and 36% of patients who had never had an HIV-related illness. Of these 71%, or 28% of the entire group, had no obvious neurological symptoms. CHARTER, therefore, suggested that HIV more than doubled the risk of brain impairment in otherwise healthy people, raising concerns that it might become even more common with age.
One study presented at BHIVA, however, found a rate of asymptomatic neurocognitive impairment of only 19% in a group of patients with suppressed viral loads, very little in excess of the general population rate. Another study found that young people who had been born with HIV had rates of neurocognitive impairment no higher than their HIV-negative siblings. This study, and a third study that looked at rates of neurocognitive impairment in the over-50s, found some evidence that some psychological tests that rely on self-report might not be detecting actual difficulties in thinking and memory, but rather people’s fear of them.
The St Mary’s Study
Dr Lucy Garvey from St Mary’s and Hammersmith Hospitals in west London reported on a survey (which won a prize for best presentation at the conference) of 101 patients who were on stable antiretroviral therapy without any obvious neurological symptoms or other illnesses. They had all had HIV for more than six months.
The study subjects were given two types of psychological test, a 20-minute computerised cognitive assessment test called Cogstate, and the International HIV Dementia Scale (IHDS), a short, validated screening test for dementia employing three simple memory and motor tasks.
Neurocognitive impairment was defined as scores more than one standard deviation below the mean age-matched population data in at least two areas of functioning – roughly within the lowest one-sixth of performance scores.
The median age of the subjects was 53, and the majority (77%) were white men. They had been HIV-positive for an average of 14 years, with a mean CD4 count of 559 and lowest-ever CD4 count (nadir) of 185. A high proportion – 25% – had hepatitis C, which is also associated with neurocognitive disorders.
The overall rate of neurocognitive impairment was 19% in this group, only 3% above the rate in the general population. The pattern of domains affected was familiar from other studies of people with HIV, in that fine muscular movement, multitasking and executive function (prioritising and planning) were particularly impaired, and CD4 nadir was associated with a high IHDS score, but nonetheless the impairments seen were slight.
“Many cohorts have reported HIV-associated neurological disorder, but their antiretroviral therapy status and health have been widely variable,” commented Dr Garvey. “This is one of the first studies to look at neurocognitive impairment only in stable HIV-asymptomatic patients on suppressive antiretroviral therapy.”
The St Mary’s team will now conduct further studies to look at neurocognitive disorder in drug-naive patients with unsuppressed HIV.
Young people and brain impairment
The results from this study were echoed by another study from St Mary’s that looked at neurocognitive function in young people who had been born with HIV. It studied 31 young people aged 16-25 (mean age 20) and compared their performance with 14 of their HIV-negative siblings. The two groups were matched for age, ethnicity (both 85% black African) and gender (33% and 29% respectively were male in the positive and negative groups). Seventy-nine per cent of the positive subjects were on antiretrovirals of whom 70% were virally suppressed (55% of the whole group).
These subjects were given the Cogstate computerised tests and the IHDS, and were also given the prospective and retrospective memory scale (PRMQ) questionnaire, a self-reported rating of problems with recall and retention of information. A minority of both groups were also given an MRI brain scan to detect signs of inflammation.
The positive and negative group had identical scores on the IHDS and on the Cogstate test in all domains. The PRMQ score was significantly worse (p=0.023) for the HIV-positive young people, and there were also high levels of activity of certain neurotransmitters in the basal ganglia area of the brain, a finding seen in other studies.
However presenter Jane Ashby commented that the PRMQ questionnaire, as a self-report, could measure subjects’ concern about memory problems as much as actual ones, and so far no study in HIV has established whether the inflammation seen in MRI scans is actually associated with neurocognitive performance.
Screening for brain impairment
The idea that some psychological tools might be reporting HIV-positive people’s fears of dementia rather than actual impairment, and might over-report neurological problems, has led London’s first dedicated HIV clinic for people over 50, at the Chelsea and Westminster Hospital, to include two ten-minute psychological questionnaires for generalised anxiety disorder and depression as standard first steps in psychological assessment of patients, only proceeding to tests for neurological function once these are eliminated.
The researchers comment that “high levels of anxiety, depression and concern about cognitive function” are common in older patients and that “memory loss, mental slowing and psychomotor disorder are common manifestations of these conditions” and should therefore be assessed and treated first.
Garvey L et al. Features of neurocognitive performance in over 100 neurologically-asymptomatic HIV-infected adults receiving combination antiretroviral therapy (cART). Seventeenth BHIVA Conference, Bournemouth. Abstract O5. 2011.
Ashby J et al. Cerebral function in perinatally HIV-infected young adults and their HIV-uninfected sibling controls. Seventeenth BHIVA Conference, Bournemouth. Abstract O30. 2011.
De Silva S et al. Over 50 Clinic: how to screen for neurocognitive disorders? Seventeenth BHIVA Conference, Bournemouth. Abstract P172. 2011.