Study Presented At ICAAC Points Out Uncertainty in Genotypic Prediction of HIV
Drug Resistance
TORONTO, Sep 18, 2000 (BW HealthWire) --
New Resistance Data on NNRTIs, Integrase
Inhibitors also Presented at ICAAC
Several common HIV mutations do not always confer resistance to antiretroviral
drugs as previously thought, according to data presented here at the 40th
Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC). This
important study highlights the complexity of genotypic resistance testing, which
relies on interpretation of mutations to predict resistance and guide HIV
treatment decisions. Actual resistance levels were determined using the
PhenoSense(TM) HIV assay, developed and marketed by ViroLogic, Inc. (NASDAQ:
VLGC).
"Resistance to anti-HIV drugs often arises from the complex interaction of
genetic mutations in HIV," said Dr. Christos Petropoulos, Vice President of
Research and Development at ViroLogic. "As this study demonstrates, the accuracy
and reliability of genotypic predictions can be problematic since there is an
incomplete understanding of the interaction of genetic mutations in HIV."
The study, conducted by Dr. Neil Parkin and a team of scientists from ViroLogic,
and titled "Discordance Between Genotype-Based Predictions of HIV-1 Protease
Inhibitor Susceptibility and Actual Phenotype in HIV-1 Isolates Containing
Mutations at Positions 82 or 90," employed PhenoSense HIV to determine the
resistance profiles of viruses with mutations at two key positions in their
genetic codes, amino acids 82 and 90 in the protease protein. Phenotypic tests,
like PhenoSense HIV, directly and quantitatively measure HIV's susceptibility by
challenging the virus' ability to replicate in the presence of antiretroviral
drugs.
Using PhenoSense HIV, researchers found that 73% of viruses with mutations at
position 82 were still sensitive to at least one drug that genotyping had
labeled ineffective, and 47% of viruses with the common mutation L90M were
susceptible to at least one supposedly ineffective drug.
Study Reveals Widespread Hypersusceptibility to NNRTIs
In other data presented at ICAAC, scientists reported that hypersusceptibility
to non-nucleoside reverse transcriptase inhibitors (NNRTIs), a commonly used
class of AIDS drugs, is prevalent among patients with previous HIV treatment
experience. Hypersusceptible HIV may be more vulnerable to treatment with
antiviral drugs, as hypersusceptibility was associated in the study with
improved treatment response. This may have important clinical implications for
the use of NNRTIs in treating HIV infection, especially after failure of prior
therapy.
Researchers from the University of California-San Diego, ViroLogic, and six
other academic research institutions examined HIV from 164 patients across the
U.S. using PhenoSense HIV, the only drug resistance test able to consistently
detect and measure viral hypersusceptibility. Their findings, in the study
titled "NNRTI Hypersusceptibility is Common and Improves Short-Term Virologic
Response," suggest that many patients on HIV therapy may benefit from testing
that can identify NNRTI hypersusceptibility.
"Our study shows that information about increased drug susceptibility, as well
as drug resistance, may be useful in optimizing patient therapy," said lead
investigator Dr. Richard Haubrich of the University of California-San Diego.
"Patients who have virus that is hypersusceptible to particular drugs may
respond better to treatment with those drugs, at least in the short term."
The investigators detected hypersusceptibility to at least one NNRTI among 24%
of the study population, and the phenomenon was particularly prevalent among
patients whose virus had grown resistant to one or more nucleoside reverse
transcriptase inhibitors (NRTIs).
The study also found that hypersusceptibility can lead to improved treatment
response. In patients with hypersusceptible virus, administration of NNRTIs
resulted in greater short-term viral load reduction and larger increases in CD4+
cell counts, compared to those patients without hypersusceptible virus.
Researchers Present Data on Integrase Inhibitor Resistance
Scientists at ICAAC presented data on the measurement of HIV resistance to
integrase inhibitors, the newest class of HIV/AIDS drugs. The study was
conducted using PhenoSense HIV, the only commercially available test able to
measure integrase inhibitor resistance.
Researchers from ViroLogic and Merck Research Laboratories examined integrase
inhibitor resistance among a wide range of virus types, including virus
resistant to many of the available AIDS drugs. In the study titled "Measuring
HIV-1 Integrase Inhibitor Susceptibility Using a Recombinant Virus-Based, Single
Cycle Replication Assay," the researchers found no cross-resistance between
integrase inhibitors and other drug classes, indicating that these drugs may be
a useful option for those patients whose virus has grown resistant to most
available antiretroviral drugs.
The researchers concluded that "the PhenoSense HIV assay can be used to evaluate
susceptibility to the newly developed class of integrase inhibitors with high
accuracy and rapid turnaround time."
"With the ongoing development of new AIDS drugs, I believe that physicians will
increasingly turn to reliable, easy-to-interpret resistance tests like
PhenoSense to help guide patient therapy," said Bill Young, Chairman and CEO of
ViroLogic. "To prepare for this, we continue to expand our test to measure HIV
susceptibility in new drug classes like integrase inhibitors and entry
inhibitors, which are currently in clinical trials."
In addition to testing for resistance to integrase and virus entry inhibitors
(e.g. fusion inhibitors, receptor antagonists), ViroLogic is also developing
drug resistance tests for hepatitis B and C.
About ViroLogic
ViroLogic is a biotechnology company developing and marketing innovative
products to guide and improve treatment of viral diseases. The Company's
proprietary technology, called PhenoSense(TM), tests for drug resistance and
susceptibility in viruses that cause serious diseases such as AIDS, hepatitis B
and hepatitis C.
ViroLogic's first product, PhenoSense HIV, is a test that directly and
quantitatively measures resistance of a patient's HIV to antiviral drugs. The
test results provide physicians with important information to help select
appropriate drugs for their HIV patients. The Company is also developing
PhenoSense products for other viral diseases and intends to use the results of
its PhenoSense tests and other clinical data to develop its Therapy Guidance
System(TM) (TGS(TM)), an interactive database to help physicians guide patient
therapy.
Certain statements in this press release are forward-looking. These
forward-looking statements are subject to risks and uncertainties and other
factors, which may cause actual results to differ materially from the
anticipated results or other expectations expressed in such forward-looking
statements. These risks and uncertainties include, but are not limited to,
whether PhenoSense(TM) testing will achieve market acceptance, whether payers
will authorize reimbursement for our products, whether we will be able to expand
our sales and marketing capabilities, whether we encounter problems or delays in
automating our process, whether we successfully introduce new products using our
PhenoSense(TM) technology, whether intellectual property underlying our
PhenoSense(TM) technology is adequate, whether we are able to build brand
loyalty, and other risks and uncertainties detailed in our final Prospectus that
is part of our Registration Statement on Form S-1, as declared effective by the
SEC on May 1, 2000 (File No. 333-30896).
CONTACT: ViroLogic, Inc.
Sidney Ho, Director of Public Affairs, 650/635-1100, x206
sho@virologic.com
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