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University of Pittsburgh researchers are
developing a method for detecting dormant HIV in asymptomatic patients – an
important step in identifying a cure for the virus.
Scientists working at the University of Pittsburg
School of Public Health, led by Phalguni Gupta, have developed a test that they
describe as “faster, less labor-intensive, and less expensive than the current
‘gold standard.’” It also seems to be much more effective.
In experiments, their so-called TZA test was able
to detect a 70-fold increase in the amount of “hidden” HIV found in
asymptomatic patients with undetectable viral loads.
In a study published in the journal Nature
Medicine, the researchers describe the test, which they hope could hold part of
the answer to a long-standing question among doctors trying to find a cure for
HIV: How can we determine when someone is truly cured?
“All this time infected people are taking the
drugs and we don’t see any virus in the plasma, but actually the virus is
hiding in the cells,” said Gupta, senior author on the study and vice chair of
the department of infectious diseases and microbiology at the University of
Pittsburg.
Current medicine has revolutionized the lives of
those living with HIV. Thanks to antiretroviral treatment, known as ART, an
infection that was once considered a death sentence has since become a
manageable condition. But the treatment is still not able to completely
eliminate HIV from the body.
HIV spreads throughout the body by infecting CD4+T
cells, commonly referred to as T cells, which are a kind of white blood cells
that plays an important role in protecting the body from infection. Currently,
antiretroviral treatment can suppress HIV in active cells to levels that are
virtually undetectable — to as little as one virus per million CD4+T cells.
But even when the viral load is undetectable,
dormant HIV can remain in inactive CDT+4 cells. This so-called “latent HIV
reservoir” is what the team at the University of Pittsburg hopes to identify
and characterize. If the reservoir could be effectively reduced, patients would
be able to go off of antiretroviral treatment while maintaining undetectable
viral levels.
“We have to eradicate the virus in the latent
condition — once we do, people can’t live without any drug,” Gupta said.
“That’s the ultimate goal.
Last fall, a team in the United Kingdom announced
the development of a “kick and kill” drug that they claimed would be able to
draw HIV out of inactive cells and stimulate the immune system against infected
cells. But before such a drug can be used, Gupta explained, scientists have a
precise way to quantify the latent HIV reservoir, which would allow for the
effectiveness of the drug to be measured.
While most of the DNA of HIV that has integrated
into the inactive cells is defective and therefor unable to cause infection in
the patient, creators of the TZA test note that there is the potential for this
dormant HIV to be awakened, replicating, and causing a relapse of an otherwise
healthy patient. For this reason, researchers say its crucial not only to
identify this latent HIV reservoir, but also test its ability to replicate.
Gupta and his team have done this by identifying a
specific gene that is activated only when replicating HIV is present. Once the
replicating HIV is flagged, scientists say that technicians should be able to
quantify it with greater ease.
Currently, this process is done by way of a test
called a “quantitative viral outgrowth assay,” or Q-VOA, which authors describe
as having a number of drawbacks. Aside from giving a minimal estimate of the
latent HIV reservoir, the test requires a large volume of blood, and is
labor-intensive, time-consuming, and expensive.
The TZA test, by contrast, requires much less
blood, which offers a major advantage in pediatric applications. It is also
expected to be cheaper, more accurate, and able to deliver results in just one
week ¬— half the time needed to grow out a viral sample with the Q-VOA test.
While optimistic about the results, Gupta and his team are cautious to avoid
sweeping conclusions about the significance of the test.
Currently the only person to have been cured of
HIV is American Timothy Brown, the so-called Berlin patient. He received a bone
marrow transplant from a donor with natural immunity to the virus.
“This would be used as a tool that would give
technicians a chance to know how much virus is present,” said Gupta. “But I’m
not making a big thing of it until we do a bigger lab study.”
