Gene Sequencing Helps Doctors Individualize HIV Patients’ Treatment Plans
Viral genotypic resistance testing sequences the genes of HIV, allowing doctors to individualize patients' treatment regimens, choose the most effective anti-HIV drugs from the approximately 15 available and avoid ones to which the virus is resistant, the New York Times reports. Toronto-based Visible Genetics has developed a new genotypic test to search for mutations in the virus' genes that confer drug resistance and, pending FDA approval expected early this year, the company hopes to donate sequencers to doctors' offices, hospitals and clinical laboratories to which it will then sell its test kits.
'Eeny, Meeny, Miney,' Geno
Gene sequencing, once seen as a "future promise," is becoming practice, as the fight against AIDS has companies "racing" to establish themselves. Gene sequencing is one of two types of resistance tests currently offered. One test, phenotyping, involves testing several different drugs on a viral sample to find the one that works best. Although this seems to be the more "obvious" method, it is "extremely difficult" to perform and relatively expensive. Genotypic testing, however, costs roughly half of the $700 to $1,000 charged for phenotyping, and results are available in one to two weeks, half the time of the other test. Because of the lower cost, Laboratory Corporation of America reports a 3:1 ratio of genotypic to phenotypic tests performed. Resistance testing has had an "enormous impact" on drug therapy, according to Dr. Gary Cohan, managing director of the Pacific Oaks Medical Group in Beverly Hills, Calif. "Before resistance testing, we used what I lovingly referred to as the eeny, meeny, miney, mo method [of drug selection]," he added.
Despite endorsements from the Department of Health and Human Services and the International AIDS Society, some "experts" remain skeptical of the testing, arguing that the benefits to patients "have not been adequately proved." Charles Flexner of the AIDS Clinical Trials Unit at the Johns Hopkins University School of Medicine said that doctors are being "rushed" into using resistance testing "because the technology is available." He added that the tests are "prone to error" and the results are "too complicated for most doctors to interpret." There are more than 100 possible mutations in the two genes that are sequenced during the genotypic test, and because of HIV's mutability, "novel mutations" keep appearing. A technician must undergo three months of training to operate Visible's test. "Given the difficulties of testing," many physicians and hospitals may choose to send blood to clinical labs that have already developed their own tests, the Times reports. Visible, however, hopes that FDA approval will make its test the "de facto standard," replacing the "home brew" tests currently used in clinical labs. But the laboratories claim they are outside of FDA regulation and not required to use Visible's test, if approved, because they perform tests in-house and are not selling them to an outside market, as Visible does. With 300,000 patients currently receiving multi-drug therapy, and an average time of treatment failure of six months, Visible CEO Richard Daly predicts the struggling company will turn a profit four to five quarters after FDA approval. He anticipates 500,000 to 800,000 genotypic tests will be performed each year in North America, representing $100 million to $200 million in annual sales. Resistance testing also offers hope for treatments for cancer, Alzheimer's, diabetes and cardiovascular disease, Jorge Leon, vice president for applied genomics at Quest Diagnostics, said. The tests are a "model for what's going to happen in the future," he added (Pollack, New York Times, 1/17).