Not all immune systems are created equal.
Without appropriate antiretroviral treatment, most people who have been
infected with HIV will progress towards more serious disease – some more
slowly, others more quickly. However, about one-in-a-hundred HIV-positive
people show a natural ability to at least partially control HIV infection and
really slow down disease progression. These so-called ‘long-term
non-progressors’ are able to maintain close-to-normal health, low viral loads,
and high CD4 cell counts for up to three decades (so far), without the need for
treatment. In addition, some non-progressors, so-called ‘elite controllers’,
are able to maintain ‘undetectable’ viral loads (i.e. below 50 copies/ml)
without the use of antiretrovirals.
Research into long-term non-progression
began in the early 1990s when researchers in San Francisco realised that they had patients
infected between 1978 and 1980, in the very earliest phase of the epidemic, who
were still healthy, with normal immune systems and very low levels of HIV in
their blood. The research,1 by Susan Buchbinder and colleagues
caused excitement at the 1993 International AIDS Conference in Berlin, and led to the
establishment of other studies around the world. It also led to an
understanding that the phenomenon was more common than expected.
“If you talk to anyone who has a practice
of 300 HIV patients, they will have [an ‘elite controller’],” noted Bruce
Walker of Harvard University Medical School during the 2006 launch of the HIV
Elite Controllers Consortium, an international collaboration between
researchers in the United States, Canada, Europe and Australia.2
Naturally, there has been great interest in
why some people are able to control their HIV for long periods of time without
antiretrovirals. Part of the reason may be due to the particular strain of
virus that person has been infected with. HIV has evolved into a wide variety
of strains – some more potent, some less so. Infection with a ‘wimpy’ strain of
virus may mean it does less damage and is more easily controlled by the immune
system.
On the other hand, it may have something to
do with characteristics of the infected person, rather than the virus – these
are known as ‘host factors’. Professor Frances Gotch and her colleagues from Imperial College,
based at London’s Chelsea
& Westminster
Hospital, have identified
a number of long-term non-progressors and, together with several other groups
of researchers worldwide, have shown that there may be a genetic component to
non-progression – some people may simply be lucky enough to have inherited a
protective genetic make-up from their parents.
For those lucky enough to be ‘elite
controllers’, however, both factors – ‘wimpy virus’ and inherited genes – may
apply.
Of course, we cannot pick and choose the
virus we are infected with or the genes we are born with. But Prof. Gotch and
others are investigating what we might be able to learn from the more
genetically fortunate. Once we have identified the characteristics that keep
non-progressors well, the next question is whether it is possible to induce
these characteristics in others.
“Of most interest to us as immunologists,”
Prof. Gotch tells HTU, “is the fact
that many long-term nonprogressors have exceptionally good HIV-specific immune
responses.” Using sophisticated technology to measure the quantity and quality
of such HIV-specific cellular immune responses, Prof. Gotch and her colleagues
at Imperial College have found that their group of long-term non-progressors
“show particularly high levels of CD8 ‘killer cells’ as well as high levels of
effective CD4 T helper cells in the blood; together these seem able to keep the
levels of virus down.”
'Killer' cells
While most people with HIV are well acquainted
with their CD4 cells, which communicate with other immune cells and co-ordinate
the overall immune response, CD4s are actually just one of many types of immune
cells that play distinct but interlocking roles in fighting infections. CD8
cells, often overlooked, are also extremely important. CD8 cells, in addition
to being 'killers', are also able to act as 'suppressors' of viral replication.
Killer CD8 cells destroy infected human cells, sacrificing them in a bid to
keep infection from spreading further.