The prescription for old age

What will happen as the HIV-positive population grows older is already the topic most frequently suggested by readers for HIV Treatment Update to cover. It was recently the subject of the annual community symposium at the autumn conference of the British HIV Association.¹Gus Cairns reports.

Will HIV make us age quicker or die sooner? Will we have different needs to the rest of the ageing population? And will those needs be met, or do we need to start campaigning for them now? There’s an awful lot we still don’t know about how HIV and age may affect each other.

Part of the problem is that to any geriatrician (someone who specialises in the medical needs of older people) ‘old’ means over 70 at least, and there simply aren’t the numbers of people this age in the positive population yet to really know if HIV will affect us profoundly - though we are soon going to start finding out.

So far, there is frank disagreement amongst clinicians as to the likely impact of HIV on ageing. At the British HIV Association (BHIVA) autumn conference, a presentation by a geriatrician, Dr Peter Kroker of the Chelsea and Westminster Hospital, predicted that few people with HIV would belong to the group of really hale and hearty elders – people who survive into their 80s and 90s with reasonably good health.

This was immediately challenged, from the audience, by another physician from the same hospital, BHIVA founder Professor Brian Gazzard, who said that he felt the additional disease burden HIV may place on the elderly will only be a relatively small one.

“Most of my older patients are fit. The data that we will age prematurely is not there,” he said.

The older HIV patient: some facts

So what do we know? At the seminar, Brighton’s senior HIV consultant, Martin Fisher, outlined the greying of the HIV-positive population. One in six of the HIV-positive population of the UK is now over 50, and in Brighton that figure rises to one in three. There are now about 2500 over-60s being seen for HIV care in the UK compared with 350 in 2000, and over 500 over-70s.

Not all of those are long-term survivors diagnosed when young. The proportion of over-50s with HIV who have been diagnosed in the last year is the same as in the HIV-positive population generally – one in six. Nearly a third of those were over 60.

This doesn’t mean they’ve all acquired HIV recently. One-in-three people with HIV has a CD4 count below 200 cells/mm³ at diagnosis, usually because they’ve delayed testing; but in the over-50s that rises to 60%.

“Late diagnosis in the older person really is bad news,” said Fisher. If they don’t start taking antiretrovirals (ARVs) immediately, those over 50 are more likely than younger people to develop an AIDS-related condition, to do so at higher CD4 counts and, if they do, to die from it.

If they’re on treatment, though, Fisher said, the situation is less clear. CD4 counts in older people on treatment do rise more slowly and achieve lower peak levels. On the other hand, older people generally adhere to treatment better and are more likely to achieve viral undetectability. This is because although they are more likely to get drug side-effects, they tend to be more stoic about them and therefore less likely to discontinue treatment.

While it's clear that untreated HIV infection mimics age, it's not at all clear that people who are on treatment from diagnosis will age prematurely.

Professor Brian Gazzard

We do know that, on average, HIV shaves about ten years off the future life expectancy of people with HIV, whatever age they are right now, compared with a similar HIV-negative person (see How long have I got, doc? in HTU 195): about as much as being a heavy smoker. But older people on HIV treatment appear to have no additional risk of death, compared with younger HIV-positive people, over and above the increased risk that comes with age for anyone.

People with HIV, even discounting the effect of factors like smoking, are about 60% more likely to get heart disease and 75% more likely to get kidney problems than the general population, however, added Fisher. And as well as the well-known cancers related to viral infections (Kaposi’s sarcoma, anal and cervical cancer, lymphoma, liver cancer), we are also more than twice as likely as a similar HIV-negative person to get lung cancer and many other common ones.

There is also the vexed question of brain impairment and dementia. We do know that about half of all people with HIV have a measurable degree of poor performance when it comes to thinking, concentration and memory (see Scattered pictures, HTU 186), and that the risk rises with age. However, we don’t know how severe this will get in the average person.

We also know that life expectancies continue to improve. A person newly diagnosed with HIV at the age of 35 between 1996 and 1999 could only expect to live till 60. Someone of the same age diagnosed now can expect to live till 73, according to a 2008 study in The Lancet,² and the picture continues to improve.

Both Martin Fisher and Peter Kroker, however, were worried that this improvement in lifespan may abruptly reach a limit as people with HIV hit their mid-70s.

The cause of old age

Peter Kroker explained this. He started off his presentation quite optimistically, pointing out that, ever since the second world war, “Every ten years, in virtually the whole western world, we have gained about two years in life expectancy, and we don’t really know why.” In 1900, 50% of people died before they reached the age of 45. Now only 4% of people die before this age.

It used to be thought that ageing was simply a matter of the stresses of the environment (ranging from social inequality through smoking to viral illnesses) eventually outpacing the ability of the body’s organs to recover from them. This probably still explains inequalities in life expectancy, such as the fact that men in Kensington and Chelsea, west London, live on average to 84, but in Glasgow City only to 71.³

It became clear more recently that there wasn’t one primary cause of ageing, however. Instead, researchers have uncovered two very intriguing findings. Firstly, there appears to be a rather precise maximum lifespan which, if everything else is perfect, we are set to die at: “Everything seems to be finely calibrated to achieve a maximum lifetime of about 120 years,” commented Kroker.

Secondly, it has become clear that ageing is not just a question of gradual decline, but that at the end of life, a mysterious process takes over that accelerates ageing. It’s as if at a certain point people lose their resilience so that “something whose physiological impact is relatively slight, such as a hip fracture, triggers rapid ageing”. Many of us may have had a feisty granny who survives into late old age but who suddenly seems to ‘give up’ after some relatively trivial event.

The sign that the person has entered this zone may be that they start to display “frailty”. This is a specific clinical syndrome in older people which includes unintentional weight loss, muscular weakness, exhaustion and low activity, and Fisher said that his older HIV-positive patients were at least three times more likely to develop frailty as other old people, especially if they have a low CD4 count.

There are even some clues, from animal studies, as to what might trigger this self-destruct cycle. Researchers produced longer lifespans in middle-aged mice by feeding them carefully calibrated doses of an immune-suppressant drug called rapamycin (Sirolimus).⁴ Rapamycin works by making immune cells sluggish, so they proliferate less rapidly. Might the sudden ageing seen at the end of life be a phenomenon like AIDS – an overactivation of immune cells which burns out the system?

Will HIV accelerate ageing?

This might spell trouble for people with HIV, and Kroker is concerned that, as people age, HIV infection – whether treated or not – may have characteristics that mean that people with HIV age quicker.

He is most concerned about the threat of cancer. “I expect that the effects of HIV will increasingly be augmented by the ageing process,” he warned the conference, adding that “I especially expect cancer rates to rise exponentially when patients come towards the end of their 60s and older.”

He quotes from a study in The Lancet that compared patients with HIV to patients who had received transplants and were on immune-suppressant drugs, in order to try and compare cancer rates in two groups of people with low CD4 counts.⁵ The researchers found that both types of lymphoma and liver cancer were at least twice as common in people with HIV as they were in transplant recipients. Given, however, that these cancers are related to Epstein-Barr virus and the hepatitis B and C viruses, lifestyle factors in people with HIV can’t be ruled out as the reason for higher rates of cancer.

Fisher suggested that HIV infection gives people a biological age considerably in advance of their actual one: so cardiovascular and kidney function is often characteristic of people ten years older, bone mineral density of people 15 years older and so on. And Kroker points out that HIV infection and age produce very similar immune defects.

One could split the population into groups in terms of mortality, he said. Leaving aside the 4%, previously mentioned, who died aged under 45 of things like accidents, childhood cancer, and so on, there are two distinct categories. There are the two-thirds of people who live beyond the age of 75; in this group the average life expectancy is 90 and they essentially die of old age. This leaves 28% of people who die between the ages of 45 and 75. This includes people where bad genes, bad luck or poor lifestyle has led to a failure to achieve the maximum lifespan.

“I fear that most HIV patients will be in this second category,” was Kroker’s sombre conclusion.

Looking on the brighter side

Brian Gazzard isn’t so sure. He explained the comments he made at the seminar to HTU.

“In terms of the biochemistry,” he says, “the problem is one of finding the right controls. The studies may have established that there is more immune activation [and potential burnout] in people with HIV compared to the clean-living laboratory assistants they tend to use as controls.

“But what you need to do is compare them to people with the same lifestyles who happen to be HIV-negative: gay men, people from Africa, and so on. Gay men are more likely to have other infections like CMV” (cytomegalovirus, which may cause cancers).

“The same applies to brain impairment. Do you compare it to people who’ve never touched a drug in their lives, to people who’ve taken drugs in the past, or to people who were on crystal meth last night?”

A clue he may be right was provided by a survey at St Thomas’s Hospital (quoted in Scattered pictures). This found more brain impairment in gay men with HIV than in the general UK population – but scarcely less in the HIV-negative gay men it picked as controls.⁶

“Then,” says Gazzard, “we need to appreciate that this is all about relative risk, not absolute risk. Some of these cancers are rare. It’s clear there is a somewhat raised risk of them in people with HIV, but twice the risk of something rare is still rare.

“While it’s clear that untreated HIV infection mimics age, it’s not at all clear that people who are on treatment from diagnosis will age prematurely; the length of time untreated may turn out to be crucial.

“I’m against predicting a holocaust where one has not yet happened. I think the evidence that there will be a lot of dementia and premature ageing in people with HIV is still pretty slim.”

Complex care needs

Whichever scenario applies to people with HIV, no one is in disagreement that as we age we will present with complex care needs, and it may be a bit of a puzzle as to which doctors or set of specialists should be in charge of our health care.

We need better links between the NHS and social care services, and better preventative programmes to help people live healthier, fitter and longer lives.

Garry Brough, Terrence Higgins Trust

Should older people with HIV be managed differently from their younger peers? The problem is that there are very few data to go on, because few drug studies have been done in older people with HIV, as they often have other conditions besides HIV and are frequently on other medications.

Despite his early gloomy predictions, Peter Kroker says that, with ideal management, people with HIV “have the potential to make it into their mid-90s and beyond. But how do I help them get there?”

And who should be in charge of their care? “Do we retrain HIV physicians in general medicine?” asks Martin Fisher. “Or train other specialists to take an interest in HIV? Do we persuade gerontologists who normally only deal with the over-80s to get involved? Do we make a concerted effort to re-engage with GPs, who are quite used to managing older patients with common and complex needs?

“The ideal way forward is probably a combined clinic with specialists physically in the same room, but this may be difficult for smaller clinics and given the direction the NHS is following.”

From outside HIV, Peter Kroker is much clearer. “I don’t think geriatricians should manage antiretroviral therapy,” he says. “I don’t think I would have the time or the intellectual capacity to look after another 20 HIV patients in an outpatients’ clinic that already has 8000 attendances a year. This group would get lost in such a set-up.”

Social care needs

Whatever will happen to HIV-positive seniors over the next few years, we will not only have medical treatment needs, but also social and care needs.

Garry Brough, who works for the Terrence Higgins Trust (THT), gave the third presentation at the community symposium. He ran through the findings from the 50 Plus survey that THT and Age UK (the new charity arising from the merger of Help the Aged and Age Concern) conducted and which THT’s Lisa Power wrote about in HTU this July (see Will a long life be a good one? in issue 198).

“We need better links between the NHS and social care services,” says Brough, “and better preventative programmes to help people live healthier, fitter and longer lives.

“We should especially concentrate on exercise,” he adds. “This is one of the very few things that makes a real difference to most heart problems, bone density, blood pressure, cholesterol levels and depression, as well as helping to reduce social isolation.” Studies have also shown that exercise, in both middle⁷ and old⁸ age, can cut the prevalence of dementia by 40 to 50%.

The prescription for healthy living in old age for people with HIV is, then, the same as it is for everyone. Don’t smoke, don’t stress, do exercise well, eat well, and think well. Remain interested in life and it will remain interested in you.