Other
diseases are becoming far more important than AIDS for people with HIV who have
consistent access and good response to antiretroviral treatment, and management
of age-related comorbidities will become an increasingly important aspect of
HIV medicine worldwide in the coming years, Steven Deeks argued in his keynote
address yesterday at the 7th International AIDS Society Conference on HIV Pathogenesis,
Treatment and Prevention (IAS 2013) in Kuala Lumpur.
Deeks,
from the University of California at San Francisco, has done extensive research
on both ageing with HIV and cure-related strategies. Preceding the conference,
he co-chaired a two-day Towards an
HIV cure symposium with IAS president Françoise Barré-Sinoussi and Sharon
Lewin from Monash University.
Among
people living with HIV who are on effective antiretroviral therapy, the virus is kept
under control, the immune system works pretty well and AIDS-related conditions
are uncommon, Deeks said. "For
people with drug-susceptible virus, who are motivated to take the drugs, and
who have lifelong access to therapy, AIDS is no longer the problem." Instead,
he explained, "HIV is looking a lot like other chronic diseases,"
characterised by persistent low-level immune activation and inflammation.
Several
studies have shown that HIV independently confers an excess risk for
cardiovascular disease and other non-AIDS conditions. A large US veterans
cohort study that compared HIV-positive and -negative people, matched for age and
other factors, found that people with HIV had about a 1.5-fold higher rate of
heart disease – about the same excess risk associated
with having diabetes. Effects of a similar size have been seen for bone loss,
neurological impairment, kidney disease and certain types of cancer, Deeks
noted.
Another
study found that people living with HIV who are in their fifties have as many
comorbidities, on average, as HIV-negative people 10 or 15 years older.
"It looks like [HIV] adds a
decade in terms of age-associated conditions," he said.
People with treated HIV have increased levels of
multiple markers of inflammation. And these markers – especially
interleukin 6 and D-dimer –
predict excess risk of morbidity and mortality.
"If we venture out of the HIV world into
rheumatology, cardiology and especially geriatrics, similar observations are
made," Deeks continued. "Chronic inflammation is at least predictive – and
probably causal –
of comorbidities in study after study."
Heart attacks and the like are uncommon at age 40
to 50, so HIV has not yet had a major effect on absolute numbers, but is likely
to do so as people age, he warned. "While most people with HIV are young now, as people
on therapy get older – into their sixties,
seventies and eighties – all these other diseases
could add up to problems."
"I spend my time in the clinic talking
about exercise, management of lipids, a Mediterranean diet, and so forth...We
should all be helping our patients in their forties and fifties live to their seventies
and eighties, so they're around for a cure." Steven Deeks
Furthermore, these conditions – mostly
studied so far in the US and Europe –
"are now playing out in developing world," Deeks said. "In
Africans we're seeing a higher number of comorbidities even though the
population is younger. The same thing that's happening in the US is likely
happening on a global level." These excess comorbidities and the shift to
chronic disease management could overburden already stretched healthcare
systems.
But
fortunately, Deeks continued, we can do something about it.
We know a lot about mechanisms of inflammation, why
inflammation might cause disease and targets for potential therapies, he said.
There are multiple drugs in the pipeline to try to reverse the process, as well
as increasing evidence that starting antiretroviral treatment early rather than
late may help prevent long-term residual inflammation (now being investigated
in the START study).
Now
that HIV is a chronic disease, Deeks argued, "we need to switch our focus
from acute to chronic care, which requires a whole new set of skills and
changes in the healthcare system."
Ultimately,
he concluded, the various problems associated with chronic HIV disease – excess inflammation, heart
disease, overburdened health systems, not being able to afford lifelong therapy –
"could all be addressed by a cure."
"There's
a tremendous amount of excitement and a bit of optimism that we're making
enough progress that eventually we'll be able to cure the disease," Deeks continued. "But there are also substantial barriers to curing HIV infection – and some
of them may be insurmountable."
Making
an analogy with the development of antiretroviral drugs, he suggested that cure
research is where antiretroviral therapy research was in the late 1980s, when we
were learning about pathogenesis, how to measure HIV and beginning to identify
potential targets to go after the virus.
Today
we are trying to measure residual HIV in long-term treated people and have seen
that certain agents can affect the biology of the virus. But "going after
free virus [in the blood] was a lot easier than virus hidden in cells," he
emphasised. "We have to find some ways to get in there without harming the
patient."
The Towards an HIV cure meeting featured a lot of
cutting-edge research, some of which will be presented during the week at the
main IAS conference. Researchers will talk more about the case report of a baby in Mississippi, presented at this year's Conference on Retroviruses and Opportunistic Infections (CROI), which Deeks thinks "represents a clear-cut cure". There will
be late-breaker presentations on allogeneic stem cell transplantation and small
molecules that can "upset the steady state" of the viral reservoir.
"My geriatrician [colleagues] say if you want
patients to be playing tennis in their 70s, you need to be dealing with that in
their forties," Deeks said. "I spend my time in the clinic talking
about exercise, management of lipids, a Mediterranean diet, and so forth...We
should all be helping our patients in their forties and fifties live to their seventies
and eighties, so they're around for a cure."