Genetic
mutations in the HIV virus can confer drug resistance
The
new resistance test can identify individual HIV particles with mutations
Researchers
at the Duke University Medical Center have developed a new resistance test that
can detect antiretroviral-resistant strains of HIV even if they comprise only
1% of an individual's viral load. Current tests can detect drug-resistant strains
only if they make up at least 20% of a person's viral load.
Use of this
new test could allow doctors to give patients the most appropriate treatment earlier
than is currently possible. Information on the new test appears in the journal
Nature Methods.
The
HIV genes mutate very quickly so that most people infected with HIV have many
different forms of the virus in their bodies. In some cases the mutated strains
can become resistant to HIV drugs, making treatment ineffective.
Professor
Feng Gao, who helped develop the new assay, said: "Which resistant viruses
are at hand can have important implications for the successful treatment of that
patient." He said there are already tests available to test for drug-resistant
strains in patients, but these are time consuming and can only detect resistant
strains when they are present at high levels in the patient's bloodstream.
"This
level of sensitivity makes the assay about 1,000 times more sensitive than the
most widely used assays on the market for detecting drug-resistant HIV viruses"
Gao said. "Thus, the assay may permit more accurate prediction of treatment
outcomes."
The
test also can detect when a virus molecule has more than one mutation, a capability
that no commercially available test has achieved, Gao said. This capability may
prove critical for detecting HIV strains that have become resistant to multiple
drugs, a condition that occurs often as many patients are treated with many drugs
at the same time.
How
the Test Works
HIV
genes with mutations known to be linked to drug resistance were identified. Fluorescent
tags were added to genetic material from patient blood samples. Tags designed
to stick to the mutated genes were green. Tags designed to stick to the same places
where the genes were non-mutated were red.
A
computer program counted how many molecules had each color tag attached. The test
could identify single mutated viruses in the sample The test also detected viruses
with more than one mutation If the new test is developed for clinical use as Professor
Gao hopes, it would enable such strains, even if present at only low levels, to
be identified quickly in patients. They could then be treated with the most appropriate
drugs from a very early stage to prevent drug resistant virus particles building
up.
Roger Peabody,
treatment specialist for the Terrence Higgins Trust, said: "Current tests
for resistance to HIV drugs are expensive and hard to interpret."This means
that only one in three people are offered them, despite guidelines encouraging
their use. If this research leads to a simpler and more easily used resistance
test, it will improve treatment outcomes for people living with HIV."
Professor
Gao said the test may also be useful in helping researchers to understand the
process of resistance development in patients, as it is not yet clear which combinations
of virus strains patients need to carry to develop significant drug resistance.
He said: "Our
assay can detect all types of drug resistant strains, giving a more complete picture
than other individual tests, from one blood sample."We can monitor drug resistance
over time, for example which resistant strains appear first, second, third etc.
[This] gives a lot of information on the dynamics of how resistance actually works."
He added that
the test might eventually be useful in detecting mutations conferring drug resistance
to agents causing other diseases such as hepatitis
B, hepatitis C and tuberculosis.
