As
people with HIV survive into old age there is increasing focus on conditions
associated with ageing. The evidence that HIV increases the chance of getting
things like heart disease and some cancers may cause anxiety, but for many the
biggest concern may be whether we are more likely to develop memory loss and
dementia. So it was not surprising that a group of studies on brain impairment
presented at the Conference on Retroviruses and Opportunistic Infections (CROI)
this year raised considerable concern amongst the HIV-positive community.
In
the 1980s, obvious dementia was fairly common in advanced HIV disease, but became
unusual after the introduction of AZT. Mild to moderate neurological disorders
continued to be observed in people with late-stage AIDS,1 but there
was clear evidence of improvement with the introduction of antiretroviral
therapy (ART).2 More subtle neurological symptoms seemed to persist
in some people, though, despite the life-saving therapies that were so
effectively managing other HIV-related conditions.
So
in 2002, the US National Institutes of Health launched a multi-site study
called CHARTER (it stands for CNS [central nervous system] HIV Anti-Retroviral
Therapy Effects Research). It will look comprehensively at the prevalence in
people with HIV of neurological disorders - nerve or brain damage that can be
detected by physical tests - and cognitive disorders - disorders in thinking
and memory that can be picked up in psychological tests. It will try and find
ways of predicting whether people will develop brain impairment and diagnosing
it accurately when they do.
To
some people, CHARTER’s first results were a shock.3 It found that at
study entry, out of the 1555 people with HIV in the United States whose brain
function was measured, more than half – 53% - had some form of neuro-cognitive
impairment. One in ten had clearly noticeable impairment, and one in fifty
moderate HIV-associated dementia, though the prevalence of classic ‘AIDS
dementia’ was under 1%.
So
does this mean that more than half of us are already on the way to losing our
minds? No. The evidence that HIV infection does cause a specific kind of mild
impairment in mental function is strong, but it may not resemble or have the
same causes as classic dementia, will not necessarily progress, and may not be
noticeable in daily life.
Dr
Simon Rackstraw is Medical Director of Mildmay UK, a hospital in Shoreditch,
east London, which is the UK's only specialist unit
for people with HIV-related brain impairment.
“CHARTER’s
findings are robust,” he says, “however I’m not sure how important this mild
impairment is.”
Rackstraw
continues. “Sensitive psychological tests can pick it up, but in real-life
terms it’s not interfering with daily life and people won’t be noticing
symptoms. You’re talking about the sort of things – lack of concentration,
losing things, clumsiness, forgetting names – that most of us experience at
some time or other. The effects these tests pick up are the same sort of things
that could be produced by a hangover, not enough sleep, or depression.
“The
10% with moderate impairment, however, may notice difficulty with relatively
complex tasks like driving. Other people may notice changes better than the
person concerned.
Rackstraw
explains that HIV-related brain impairment often presents a different picture
from classic dementia. “People have difficulties with executive function – the
ability to make choices and decisions – and may put things off more. Muscular
co-ordination may be lost too. On the other hand verbal fluency is usually
retained; people remain mobile and energetic, but get a bit chaotic. One of my
patients talks very convincingly about running a share portfolio – though I’m
not sure how effectively - but can’t open a can of baked beans. Classic
Alzheimer’s is more memory-oriented and people become more apathetic.”
Very
importantly, and of some reassurance to those of us who keep losing their keys,
mild brain impairment appears to be reversible. In another study presented at
CROI, Dr Scott Letendre4 cited the AIDS Clinical Trials Group Longitudinal Linked Randomized
Trials (ALLRT), a study of 1160 HIV-positive people who had been on
therapy for an average of about 20 weeks.5 At the start, despite
most people being on therapy, about 39%
demonstrated at least mild impairment.
When ALLRT re-tested participants 48 weeks later, it found that over half of people who
had impairment at baseline still had it, but in 44% of cases the impairment had apparently reversed – brain function appeared
normal again. However,
among people who had normal results at their first testing and then were re-tested,
just over a fifth (21%) had new impairment.
In
other words HIV brain impairment appears to be on average progressive amongst this group, but slowly, at a rate of
about 4% more patients with some degree of brain impairment a year. But the
average conceals the fact that nearly half of patients who have brain
impairment at one test don’t have it next time.
Even
then, it isn’t clear that HIV-related neurological impairment will always
progress to HIV-associated dementia if left untreated, or even that they’re the
same thing: there may be more than one pathological process involved in the
development of neurological problems in people with HIV.
In
addition, although age is a factor, some recent studies showed that
HIV-specific brain impairment is by no means restricted to older people. One
study from St Mary’s Hospital in west London,6
for instance, found that – relative to others of their age – HIV-related
brain impairment was actually more common in younger people with recent diagnosis. Rackstraw confirms this. “The
youngest I have currently on the ward is 22,” he says, “and I’ve treated a
number of teenagers.” HIV brain impairment and age may not always be linked.