Deborah Persaud from Johns Hopkins gave an update on the "Mississippi Baby" – now nearly four years old – who just before the conference was found
to still have HIV after having had an undetectable viral load while off antiretroviral
therapy (ART) for more than two years.
Though disappointing for the child – who has resumed ART and is in good
health – "we have learned a lot from this case and it provides a strong
rationale for moving forward with a clinical trial" of very early
combination therapy for infants, Persaud said.
"We're looking at the moment at achieving long-term remission, and how
long can we go [without antiretrovirals]," said AIDS 2014 co-chair Sharon
Lewin from Monash University. "We've realised in the past year that the
virus can really hang around for a very long time and pop up unexpectedly."
The Mississippi case "shows we need much better tools to detect HIV"
in the body and "need to learn how to eliminate long-lived
Nicolas Chomont from the Vaccine and Gene Therapy Institute in Florida
reported on the development of a new assay called Tilda that – unlike current
tests used in cure research – uses only a small amount of blood, is less
expensive, and does not require specialised equipment. Tilda "can be
implemented in pretty much any lab in the world," according to Chomont.
Dan Barouch from Beth Israel Deaconess Medical Center described a study in
this week in Nature,
showing that HIV seeds itself in cell and tissue reservoirs very soon after
sexual exposure – even before viral load is detectable in the blood. Very
early ART reduced the size of the reservoir, but it did not prevent
re-emergence of virus after treatment was stopped. "Even very early is not
early enough," Barouch said.
One strategy widely used in HIV cure research is dubbed "kick and
kill", the idea being to reactivate latent virus in resting cells. Once
the virus is "woken up" and starts replicating, it becomes visible to
the immune system and is susceptible to antiretrovirals.
Ole Schmeltz Søgaard from Aarhus University Hospital in Denmark described
his team's research using the HDAC inhibitor romidepsin to kick cells
containing dormant HIV out of their resting stage. In a small study of six people with long-term viral suppression on ART, romidepsin was indeed able to
activate latently infected cells, but "it doesn’t look like [this led to]
a significant reduction in the viral reservoir," Søgaard explained.
Results such as these indicate that neither very early antiretroviral
treatment nor agents that re-activate latent virus are likely to be enough to
enable a functional cure, or prolonged time off ART without disease
"The Mississippi and Boston
[bone marrow transplant] cases make me wonder if we will ever get rid of
the entire reservoir," said Steven Deeks from the University of California
at San Francisco. "We may get rid of big chunk of it...but we need a way
to control what's left." Deeks predicted that the cure field will move in
the direction of therapeutic vaccines or other immune-based therapies that can
be used in combination approaches.
"We should not oppose vaccine and cure research, and probably we will
need both," predicted IAS President Françoise Barré-Sinoussi. Added
Barouch, "It's two sides of the same coin."