Last month we featured a
news report about a couple of studies,1,2 presented at a recent conference,
which found that certain groups of HIV-positive people could expect to live as
long as comparable HIV-negative people.
A study from the Netherlands
looked at people who were diagnosed between 1998 and 2007 and then excluded
those who had had to go on treatment within six months of diagnosis. Once this
group, who’d mostly have been diagnosed with a low CD4 count, was excluded,
then the average remaining life expectancy of someone who was diagnosed at the
age of 25 was calculated to be 52.7 years – in other words they would die, on
average, at the age of nearly 78: just five months short of a 25-year-old
member of the general Dutch population.
This group had a high
average CD4 count of 480 cells/mm3, and the study extrapolated life
expectancy from an average of just 3.3 years of mortality data, and a maximum
of ten; we need to be careful about interpretation because, as we see below,
things may take a turn for the worse later.
The other study was an
analysis of the COHERE cohort, a group of over 80,000 HIV-positive people from more
than 30 European countries. It included all people in COHERE who had started
treatment later than 1998, thereby excluding people who had taken pre-HAART
drug regimens, who are the ones most likely to have significant drug
resistance. It didn’t estimate a life expectancy: instead it calculated
something called the standardised mortality ratio (SMR). This is the amount the
death rate in a group differs from the death rate in the general population.
The headline finding was a
correction to any assumption that most people with HIV are now living normal
lifespans. Over the whole group, which included people of every CD4 count, the
death rate was 4.4 times what you’d expect to see in 80,000 people of the same
age and sex picked at random from the general population.
However, the SMR in men whose
current CD4 count was over 500, and who had maintained it for over three years
(or just one year if you excluded injecting drug users) was 1.1: statistically,
the same as people without HIV.
There were fewer actual deaths
in women than men, but mortality in HIV-positive women was twice as high as in
women in the general population because the death rate amongst HIV-negative women
of similar age is considerably lower than in men.
There’s no doubt that life
expectancy for people with HIV, at least in the developed world, has improved
vastly since treatment became available. But is it continuing to improve? Will
more of us achieve a normal lifespan as time goes on? And what do we need to do
to ensure this happens?
Several other studies have
addressed this question in the last decade.
One of the problems
besetting life-expectancy studies is that very different groups of patients are
selected for study. For instance, a study from the USA3 found that,
from the point of diagnosis, people with HIV on average lived 21 years fewer than
HIV-negative people of the same sex and age. But one-third of this group had a
CD4 count under 200 cells/mm3, and many were not accessing health care.
Another problem is that
very different measures of mortality are used so it’s not easy to make
comparisons. These include absolute mortality, the excess mortality compared
with the general population (as in COHERE): the expected average number of years
of life lost, given this excess mortality (for
instance, smokers will lose an estimated ten years of life to their habit,
compared to non-smokers), and life expectancy.
Jonathan Sterne of the Antiretroviral Therapy Cohort
Collaboration, author of one of the studies we quote in this piece, says: “Life
expectancy is a strange concept in that it extrapolates into the future a
present state of affairs. It says: ‘Given the current mortality rates, if
nothing changes, how long can people expect to live’?
“It’s rarely going to
reflect what people’s average lifespan actually ends up being, because it can’t
take account of future developments.
“For instance, the life
expectancy of people with HIV may improve, because treatments get better. But
on the other hand, it may also unexpectedly decrease if we see in future a
sudden increase in the death rate at a certain age, or after a certain time
spent taking HIV drugs.”
There’s no doubt that life
expectancy for people with HIV, at least in the developed world, has
vastly since treatment became available. But is it continuing to
One study4 of
another cohort, called CASCADE, took account of this by observing the excess
mortality, compared with the general population, over specific two-year slots
This study found that there
were 1239 deaths in 7034 patients diagnosed between 1996 and 2006, where in the
general population you’d only expect 178.7 deaths. That means over the whole study
period deaths in people with HIV were sevenfold higher than they were in HIV-negative
However, this excess
mortality went down in every period of the study. In 1996-97 people with HIV
had 17 times the death rate of the general population. By 2004-2006 it was 3.4
times the rate.
Furthermore, because in
this study the date people were infected was approximately known, changes in
the number of excess deaths over time could be looked at.
By the year 2001, people who
had been under 35 at diagnosis were no more likely to die than the general
population in the first five years after being diagnosed, and by the year 2006
this had extended to people diagnosed under 45. By this time the ten-year death rate was also starting to
approach normal among the under-45s.
However, the death rate
amongst people diagnosed for 15 years was still very much higher than in the
general public amongst all groups: seven times higher in people diagnosed up to
the age of 25 (meaning they’d be up to 40 years old now): 5.5 times higher in
people diagnosed before 35 (so now in their 50s): and 2.4 times higher in
people diagnosed up to the age of 45 and now in their 60s.
Here’s the possible reason
why the death rates seen in this study, and the life expectancy one might
derive from them, are higher in this study than in the Dutch one that predicted
normal life expectancies. If you only look at death rates in people with HIV
for the first decade after they test positive, you may miss most of the excess
deaths, whereas CASCADE followed some people up to 24 years after infection.
In the CASCADE study the
death rate in people with HIV, as measured in 2006, was very little higher than
in the general population until about eight to nine years after infection.
After this it began to outpace the expected death rate.
Was this because eight to
nine years after seroconversion is when HIV starts to make people ill? Or were
people with HIV diagnosed before 1998 more likely to have taken suboptimal drug
regimens which led to the development of drug resistance?
Kholoud Porter of the UK
Medical Research Council says that using ‘time since infection’ rather than age
to distinguish different mortality rates was vital because “a 45-year-old may
have only just been infected, or they may have had 25 years of living with HIV
and HIV medications. If you don’t take time since infection into account you
may over- or underestimate mortality.”
Just two weeks after the
CASCADE study came out, an even larger study called the Antiretroviral Therapy
Cohort Collaboration study5 was published, which did extrapolate
life expectancy in 43,355 patients from North America and Europe.
It found that deaths had
declined, from one death per 60 patients a year in 1996-99 to one per 100 in 2003-05.
And it found that life expectancy had increased, from 36.1 years for a
20-year-old in 1996-98 (so they could, on average, expect to live till they
were 56) to 43.1 in 2003-5 (living till 63). Thirty-five-year-olds could expect
to live till 60 in 1996-99 and 72.3 years in 2003-5. But SMRs were still in the
region of six to eight times that of the general population, depending on year