of the problems with this kind of study is that like is not being compared with
like. People with HIV will have many differences other than their status and
their medication from the average member of the public, so differences in
mortality could be due to all sorts of other factors.
second study of mortality tried to get around this by comparing death rates in
people who, apart from their HIV status, were closely similar. By doing this, it
was able to tease out the proportion of deaths that were due to AIDS and
therefore whether deaths due to non-AIDS-defining illness were any higher in
people with HIV or on ART than they are in the general population.
study looked at mortality due to AIDS-defining and non-AIDS defining illness in
two long-standing US cohort studies – the Multicenter AIDS Cohort Study
and the Women’s
Interagency HIV Study (WIHS). These long-standing cohort
studies were set up in 1985 and 1993 respectively. MACS has recruited 6972 gay
men who are either HIV positive or at high risk of HIV infection (41% with HIV
at enrolment) and WIHS has recruited 4137 women who are either HIV positive or closely
matched to the HIV-positive women in terms of characteristics (38% with HIV at
study compared mortality rates between the HIV-negative cohort members and the
ones with HIV who were on combination antiretroviral therapy (cART). Because
there were not large numbers of cohort members on cART who were either young or
very old, it only looked at mortality in the ‘middle years’, between 35 and 70.
For the people with HIV it looked only at mortality subsequent to them starting
cART if they were older than 35 when they started. The study looked at
mortality up to the end of 2010, so some people could have been on cART of
various kinds for 15 years or more, if they started in the mid-1990s and were
aged 35 to 55 at the time. Average length of follow-up was in fact 10.2 years:
11.7 years in the HIV-negative people and 7.6 and 8.1 years (depending on CD4
count at cART initiation) in the HIV-positive people on cART.
high proportion of the cohorts – 60% or 6699 individuals – were included in
this study. The first and most obvious fact is that mortality was a lot higher
in the people with HIV, as you might expect: over the years, 540 out of 2953
people with HIV died (18.2%) compared with 165 out of 3854 HIV-negative people
(3.4%). In terms of annual mortality rates, this is 2.32% per year in the people
with HIV and 0.37% per year in the HIV-negative people.
researchers then divided deaths in the people with HIV into AIDS-related and
non-AIDS-related causes: 11.5% of the people with HIV died of AIDS and 6.7% of
one specific group, namely people with HIV who started cART with a CD4 count
over 350 cells/mm3, mortality due to non-AIDS illness was no higher
than it was in the HIV-negative people. However, even in this group, AIDS deaths
predominated, more than doubling mortality, so overall mortality in this group
was approximately 1% per year compared with approximately 0.4% in the HIV-negative
people. This probably reflects the fact that many people would have died in the
early years of sub-standard cART.
is reflected in the fact that if people died of AIDS-related illness, they
tended to do so much younger. Models were done that, based on the mortality
rates seen, projected the likely future mortality rates of people over 70.
These showed that in people who started cART at a CD4 count above 350 cells/mm3
and who died of AIDS, there was a 50% chance of death by the age of 54: in
those who died of non-AIDS-related illness, 50% was not reached till the age of
75, no different from HIV-negative people. Thus people starting ART early were
living near-normal lifespans as long as they avoided early death from AIDS,
probably reflecting the generally improved lifespan and vastly decreased AIDS
incidence of those who survived beyond the early 2000s.
non-AIDS-related mortality in people who started cART at lower CD4 counts,
however, was higher than in HIV-negative people. It was 66% higher in people
starting cART at CD4 counts between 200 and 350 cells/mm3 and 115%
higher in people starting it at CD4 counts below 200 cells/mm3,
reinforcing the message that starting ART early is generally better for the
health, not only because it stops AIDS-related illness. Other factors that
increased the chance of death for people on cART were smoking (50% higher AIDS mortality
and 120% higher non-AIDS mortality in smokers); depression (65% more non-AIDS
mortality and 58% more AIDS mortality); and high blood pressure (42% higher
AIDS and 30% higher non-AIDS mortality).
women in WIHS had 40% higher mortality due to non-AIDS illness than the men in
MACS, but no higher AIDS mortality.
biggest influence on non-AIDS mortality was hepatitis B or C co-infection. This
more than doubled non-AIDS mortality. HIV-negative people with hepatitis B or C
died on average eight years younger than those without, and people with co-infection on cART 15 years younger than those with HIV alone.