The recent rash of new findings all refer to individuals
diagnosed and treated very soon after infection. For people with established,
or chronic, HIV infection, these findings may raise hopes of a cure, but as yet
there is no well-documented case of a cure in a chronically infected person
apart from the unusual case of the 'Berlin patient', Timothy Brown.
Dr Tony Fauci commented, “It is a greater possibility that we
aren’t going to have a pristine cure that is going to cure everybody.”
Something more than very early antiretroviral treatment will
be needed to achieve a functional cure in people with chronic HIV infection,
scientists at the meeting agreed. Chronic infection poses a challenge because HIV infects very long-lived immune system
cells and forms a reservoir of latent, inactive virus that can restore viral
load to pre-treatment levels within weeks if fully suppressive antiretroviral
treatment is halted.
Flushing out virus from this reservoir of cells will require
the identification of agents that can activate cells and deplete a substantial
proportion of virus. One round of treatment is unlikely to be enough, and
experiments with the use of candidate agents called HDAC inhibitors are still
at an early stage.
“We also need to understand how to safely and repeatedly
activate cells over time,” said Professor David Margolis, who has been studying
the use of vorinostat and other agents to induce lately infected cells to
produce HIV. It is likely that a combination approach to activation will be
required, he went on.
Others have suggested that gene therapy – taking stem cells
from a person with HIV and engineering them to become resistant to HIV
infection – may pave the way for a functional cure in people with fully
suppressed HIV. This hope is based on the Timothy Brown, the 'Berlin patient',
who received a bone marrow transplant from a donor who lacked the CCR5 receptor
used by HIV to gain entry to CD4 cells.
“Is the Berlin patient proof of concept for gene therapy?
Not really, because he had chemotherapy which wiped out his immune system,”
said Paula Cannon of the University of Southern California. “If we don’t
completely ablate [eliminate] with chemotherapy, the patient’s immune system needs to be
re-populated gradually [by repeat infusions of genetically modified cells], so
a suitable conditioning treatment is needed in order to help infused modified
cells to home to the bone marrow."
Further advances may also be necessary in order to maximise
the contribution of antiretroviral treatment to curing HIV infection. For
example, scientists need to know more about how different combinations of antiretroviral
drugs compare in reducing immune activation, which could be important in
preparing people for curative interventions, said Professor Judith Currier of
the University of California Los Angeles. If virus in the central nervous
system proves to form an important reservoir, drugs with a greater capacity to
penetrate into the cerebrospinal fluid might be needed, she said.
Scientists also need better tools to help them evaluate
whether efforts to rid the body of HIV have worked, said Professor Sharon Lewin
of Monash University, Melbourne, Australia. Researchers will need to be able to
measure whether cells are producing infectious virus in response to
interventions designed to flush out HIV from latently infected cells, and what
proportion of cells respond to the intervention.
Gregg Gonsalves, who presented an HIV community perspective
on HIV cure research at the meeting, warned that budget cuts in Europe and
North America are “a dagger at the heart of biomedical research”. He noted that,
in the United States, federal funding for scientific research and development
will fall back to 2002 levels as a result of recent funding cuts. “Austerity is
killing the great biomedical enterprise that marked the second half of the
twentieth century,” he said.
He called on scientists to become activists in order to
stand up for HIV and other biomedical research in the face of public spending