August 1, 2006 (AIDSmeds)—Independent Forensics, an Illinois-based company
specializing in paternity testing and DNA evidence used in criminal
investigations, has begun marketing a genetic assay intended for
HIV-positive people. The test, called Basepair, looks for genetic
variations in human DNA that can affect the function of CCR5, a
receptor on CD4+ cells (also known as T4 cells) that is needed by HIV to enter cells,
reproduce, and eventually damage the immune system. Knowing which
genetic variations are present, the company suggests, may help
HIV-positive people determine if they may progress to AIDS more slowly
or quickly than usual and assist them in making important treatment
decisions. In fact, one of the genetic variations that the test looks
for has been associated with "immunity" to HIV, meaning that the assay
may be of significant interest to people who aren't infected with the
virus. But some experts question the value of such testing, in light of
the fact that the study of human genetics – as it applies to HIV
susceptibility and disease progression – is still fragmented and hardly
complete.
The study of human genetics as it relates to
medicine is a rapidly expanding research field. While genes play a role
in obvious physical characteristics, such as eye or hair color, they
also play a major role in biological processes, including the body's
susceptibility to certain diseases and the way it responds to
infections.
In recent years, a great deal of research
funded by the U.S. National Institutes of Health (NIH) has found that
specific genetic variations, or haplotypes, can affect people's
susceptibility to HIV infection and, among those already infected with
the virus, the rate of progression to AIDS. The CCR5 receptor on CD4+
cells, for example, is regulated by a gene. Some variations in this
gene can render the receptor ineffective, meaning that it can't be used
by HIV to infect cells. Other variations have more subtle effects on
CCR5, but may have a significant impact on the way HIV uses it to
enters cells, potentially resulting in slower or more rapid disease
progression.
Independent Forensics' assay identifies the nucleotides – building blocks of DNA – at
seven different positions near the CCR5 gene. Other genetic variations
examined by the test include those involving CCR2, believed to be
important among HIV-positive African Americans. It also looks for the
delta-32 form of the CCR5 gene, believed to be a genetic factor
resulting in resistance to HIV infection.
As explained
by Karl Reich, PhD, Chief Scientific Officer for Independent Forensics,
all human beings are made up of two complete copies of their genes: one
copy from their mother, the other copy from their father. "Our test
does not determine the origin of the gene, such as which copy came from
mom or dad, but it does determine the actual DNA sequence of both
copies," he said. "This is important, as each copy can affect the
function of CCR5 and therefore the progression of HIV infection."
For
example, people who inherit the delta-32 form of the CCR5 gene from one
parent can be infected with HIV, but may experience slower disease
progression. Conversely, people who inherit the delta-32 form from both
parents often have near-complete protection against infection with the
virus.
While the Independent Forensic test looks for
this delta-32 form, Dr. Reich stressed that the existence of the
delta-32 gene variant – inherited from both parents – is
very rare. "It is not a genetic ‘free pass' for immunity from HIV
infection," he says. "In fact, delta-32 individuals can still become
infected with other HIV variants and progress to AIDS," referring to
transmissible viruses that use another receptor on CD4+ cells, called
CXCR4, instead of CCR5.
The real benefit of the test,
Dr. Reich argued, is the evaluation of haplotypes that have been found
to be associated with slower or rapid disease progression. For example,
HIV-positive Caucasians who have inherited an "HHE" CCR5 variant from
both parents may progress quickly to AIDS, whereas HIV-positive African
Americans who inherit the "HHA" CCR5 variant from one parent and the
"HHF*2" variant from the other parent may experience much slower
disease progression. Slower and more rapid disease progression CCR5
haplotypes have been defined for people of both races.
"Our
goal is to provide information to clinicians and patients in order to
help them better manage their disease," he said. "HIV-positive patients
who are slow progressors may benefit from decreased drug dosages to
reduce side-effects. This information may also influence choices of
anti-HIV medications in order to decrease the rate of viral resistance.
Fast progressors may benefit from more aggressive treatment, more tests of viral load, more frequent monitoring or similar interventions."
The
test costs approximately $250, but is currently priced at $179 to mark
the launch of the assay in June. Independent Forensics hasn't yet made
an effort to push for insurance coverage, although it is interested in
doing so. The test can be ordered by doctors, or independently and
anonymously by patients, notably through the company's website. A test
packet is sent by the company, involving a cotton swab that is rubbed
around the inside of the cheek, and then shipped to the Independent
Forensics laboratory in Hillside, Illinois. DNA is extracted from the
swab and then analyzed for variations in the CCR5 gene. A report
indicating the results is then sent back to the patient or doctor.
Dr.
Reich noted that the test is not approved by the FDA, nor does it
require FDA oversight, as it is not a diagnostic test. He also
confirmed that Basepair has not been evaluated in clinical trials. The
information used to analyze test results come from the NIH-funded
studies. "We are simply taking these important results and making them
available for a competitive price to the public," he says.
Not
all experts believe that CCR5 haplotype testing is useful, at least not
outside the realm of scientific research. John Moore, PhD, Professor of
Microbiology and Immunology at Weill Cornell Medical College in New
York and an active researcher in the field of human (host) genetics as
it relates to the entry of HIV into cells, does not recommend that the
test be used by healthcare providers or patients. The use of this test
in the medical management of HIV, he said, "is a mistake, given the
present state of the science. CCR5 genetics are but one contribution to
disease progression rates, and information on CCR5 genetics, taken in
isolation, could be highly misleading."
Dr. Moore also
indicated that he is unaware of any data indicating how this
information could be used to influence treatment options. "I would
think drinking a cup of tea, pouring the dregs away and looking at the
pattern of the tea leaves would be just as valuable right now," he
wryly commented.
For Dr. Reich, the time is right to
begin using genetic information to help personalize medicine and to
address the individual needs of patients. "There are many good examples
where knowing the genetics of the host improves outcomes, including
reduced costs, decreased errors, improved diagnostics, and sometimes
all four," he said. "However over hyped ‘personalized medicine' may be
in the media, the tide of genetic information is in fact, irrevocable."
At the same time, he conceded that, "CCR5 genetics are one contribution
among many and should not be taken in isolation or as the entire story
of host-HIV interaction."
