August 1, 2006 (AIDSmeds)—Independent Forensics, an Illinois-based companyspecializing in paternity testing and DNA evidence used in criminalinvestigations, has begun marketing a genetic assay intended forHIV-positive people. The test, called Basepair, looks for geneticvariations in human DNA that can affect the function of CCR5, areceptor on CD4+ cells (also known as T4 cells) that is needed by HIV to enter cells,reproduce, and eventually damage the immune system. Knowing whichgenetic variations are present, the company suggests, may helpHIV-positive people determine if they may progress to AIDS more slowlyor quickly than usual and assist them in making important treatmentdecisions. In fact, one of the genetic variations that the test looksfor has been associated with “immunity” to HIV, meaning that the assaymay be of significant interest to people who aren’t infected with thevirus. But some experts question the value of such testing, in light ofthe fact that the study of human genetics – as it applies to HIVsusceptibility and disease progression – is still fragmented and hardlycomplete.

The study of human genetics as it relates tomedicine is a rapidly expanding research field. While genes play a rolein obvious physical characteristics, such as eye or hair color, theyalso play a major role in biological processes, including the body’ssusceptibility to certain diseases and the way it responds toinfections.

In recent years, a great deal of researchfunded by the U.S. National Institutes of Health (NIH) has found thatspecific genetic variations, or haplotypes, can affect people’ssusceptibility to HIV infection and, among those already infected withthe virus, the rate of progression to AIDS. The CCR5 receptor on CD4+cells, for example, is regulated by a gene. Some variations in thisgene can render the receptor ineffective, meaning that it can’t be usedby HIV to infect cells. Other variations have more subtle effects onCCR5, but may have a significant impact on the way HIV uses it toenters cells, potentially resulting in slower or more rapid diseaseprogression.

Independent Forensics’ assay identifies the nucleotides – building blocks of DNA – atseven different positions near the CCR5 gene. Other genetic variationsexamined by the test include those involving CCR2, believed to beimportant among HIV-positive African Americans. It also looks for thedelta-32 form of the CCR5 gene, believed to be a genetic factorresulting in resistance to HIV infection.

As explainedby Karl Reich, PhD, Chief Scientific Officer for Independent Forensics,all human beings are made up of two complete copies of their genes: onecopy from their mother, the other copy from their father. “Our testdoes not determine the origin of the gene, such as which copy came frommom or dad, but it does determine the actual DNA sequence of bothcopies,” he said. “This is important, as each copy can affect thefunction of CCR5 and therefore the progression of HIV infection.”

Forexample, people who inherit the delta-32 form of the CCR5 gene from oneparent can be infected with HIV, but may experience slower diseaseprogression. Conversely, people who inherit the delta-32 form from bothparents often have near-complete protection against infection with thevirus.

While the Independent Forensic test looks forthis delta-32 form, Dr. Reich stressed that the existence of thedelta-32 gene variant – inherited from both parents – isvery rare. “It is not a genetic ‘free pass’ for immunity from HIVinfection,” he says. “In fact, delta-32 individuals can still becomeinfected with other HIV variants and progress to AIDS,” referring totransmissible viruses that use another receptor on CD4+ cells, calledCXCR4, instead of CCR5.

The real benefit of the test,Dr. Reich argued, is the evaluation of haplotypes that have been foundto be associated with slower or rapid disease progression. For example,HIV-positive Caucasians who have inherited an “HHE” CCR5 variant fromboth parents may progress quickly to AIDS, whereas HIV-positive AfricanAmericans who inherit the “HHA” CCR5 variant from one parent and the“HHF*2” variant from the other parent may experience much slowerdisease progression. Slower and more rapid disease progression CCR5haplotypes have been defined for people of both races.

“Ourgoal is to provide information to clinicians and patients in order tohelp them better manage their disease,” he said. “HIV-positive patientswho are slow progressors may benefit from decreased drug dosages toreduce side-effects. This information may also influence choices ofanti-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.”

Thetest costs approximately $250, but is currently priced at $179 to markthe launch of the assay in June. Independent Forensics hasn’t yet madean effort to push for insurance coverage, although it is interested indoing so. The test can be ordered by doctors, or independently andanonymously by patients, notably through the company’s website. A testpacket is sent by the company, involving a cotton swab that is rubbedaround the inside of the cheek, and then shipped to the IndependentForensics laboratory in Hillside, Illinois. DNA is extracted from theswab and then analyzed for variations in the CCR5 gene. A reportindicating 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 itrequire FDA oversight, as it is not a diagnostic test. He alsoconfirmed that Basepair has not been evaluated in clinical trials. Theinformation used to analyze test results come from the NIH-fundedstudies. “We are simply taking these important results and making themavailable for a competitive price to the public,” he says.

Notall experts believe that CCR5 haplotype testing is useful, at least notoutside the realm of scientific research. John Moore, PhD, Professor ofMicrobiology and Immunology at Weill Cornell Medical College in NewYork and an active researcher in the field of human (host) genetics asit relates to the entry of HIV into cells, does not recommend that thetest be used by healthcare providers or patients. The use of this testin the medical management of HIV, he said, “is a mistake, given thepresent state of the science. CCR5 genetics are but one contribution todisease progression rates, and information on CCR5 genetics, taken inisolation, could be highly misleading.”

Dr. Moore alsoindicated that he is unaware of any data indicating how thisinformation could be used to influence treatment options. “I wouldthink drinking a cup of tea, pouring the dregs away and looking at thepattern of the tea leaves would be just as valuable right now,” hewryly commented.

For Dr. Reich, the time is right tobegin using genetic information to help personalize medicine and toaddress the individual needs of patients. “There are many good exampleswhere knowing the genetics of the host improves outcomes, includingreduced costs, decreased errors, improved diagnostics, and sometimesall four,” he said. “However over hyped ‘personalized medicine’ may bein the media, the tide of genetic information is in fact, irrevocable.”At the same time, he conceded that, “CCR5 genetics are one contributionamong many and should not be taken in isolation or as the entire storyof host-HIV interaction.”