The Bay Area Reporter - June 29, 2000
David Batterson

Data From NARVAL study

Visible Genetics Inc. reported that preliminary six-month data from the NARVAL study showed a benefit to HIV patients who received HIV drug-resistance genotype testing over those patients who received standard care treatment. The NARVAL study - a French study - looked at the value of drug resistance testing in HIV treatment and patient management.

The 24-week data presented involved a total of 541 patients enrolled into three groups: standard of care, phenotyping, and genotyping. This is the largest prospective resistance testing study presented to date.

Patients in the study consisted of heavily pre-treated patients who had received a median of seven prior HIV drugs; they had an average viral load of 4.3 log copies/ml and an average CD4+ count of 300 cells/ml. The standard of care group was treated without any resistance test information provided to the physician. In the other two groups, resistance testing was performed either by genotyping or phenotyping.

Visible Genetics' Trugene HIV-1 Genotyping Kit was used in the genotyping group. Results showing the percent of patients achieving viral suppression (less than 200 copies/ml), at 24 weeks were 36 percent for genotyping, 27 percent for standard of care, and 26 percent for phenotyping. Results showing the percent of patients achieving viral suppression at both 12 and 24 weeks were 29 percent for genotyping, 17 percent for standard of care and 22 percent for phenotyping.

Visible Genetics CEO Richard Daly said the company was "pleased at the further confirmation that drug resistance testing using genotyping appears to be of benefit in the management of HIV patients undergoing antiretroviral therapy. These data are consistent with results from previous studies and provide a compelling argument for the use of genotyping in HIV patient management."

In the last six months, support for resistance testing has grown significantly. In May, the International AIDS Society recommended drug resistance testing after first and multiple treatment failures.

Visible Genetics Inc. is a leader in the emerging field of pharmacogenomics, which uses genetic information in the identification and analysis of genes to improve patient care and reduce health care costs. VGI manufactures and markets high performance automated DNA sequencing systems and complete kits for the analysis of genes linked to disease. More information is available at www.visgen.com.

Studies show accuracy of PhenoSense test

A number of studies presented at the workshop demonstrated the superior accuracy and sensitivity of PhenoSense HIV, a phenotypic HIV drug resistance test developed and marketed by ViroLogic Inc. Phenotypic tests such as PhenoSense HIV directly measure the resistance of a patient's HIV to antiviral drugs, and help physicians optimize therapy for HIV patients.

Several studies, the company stated, add to the growing body of research indicating phenotypic testing is superior to other methods in its ability to measure resistance and detect subtle differences in HIV's makeup that can affect the course of treatment, even before clinical symptoms are observed.

One study pointed out the potential clinical significance of a key distinction between the two HIV resistance testing methods - genotyping and phenotyping. This presentation focused on the differences between the two resistance testing methods. The study examined the drug resistance profiles of HIV patients by using PhenoSense HIV - which directly measures drug resistance - as well as a genotypic test, which predicts resistance by analyzing patterns of genetic mutations in a patient's virus.

Through use of PhenoSense HIV, researchers showed that viruses with two common "primary" mutations, previously believed to confer drug resistance, often remain vulnerable to many AIDS drugs.

Dr. Neil Parkin, senior scientist at ViroLogic and lead author of the study said "the phenotypic assay was able to provide a correct measure of resistance that looked beyond the accepted genotypic interpretations, providing information that can help physicians make better treatment choices for their patients."

ViroLogic is a biotechnology company developing and marketing innovative products to guide and improve treatment of viral diseases. Its proprietary technology called PhenoSense tests for drug resistance and susceptibility in viruses that cause AIDS, hepatitis B, and hepatitis C.

Results of Antivirogram phenotypic HIV resistance test

Data presented showed that HIV patients whose physicians used the results of Antivirogram - Virco's phenotypic HIV resistance test - to guide their choice of therapy, received more active drugs and responded much better than those who did not. This was the first major prospective clinical trial to show the benefit of an HIV phenotypic drug resistance test, in contrast to the traditional approach of using medical history when switching HIV therapy.

"The final analysis of this randomized, prospective trial provides important evidence that using phenotypic resistance testing to guide therapeutic decision making improves the outcome for our patients," said Dr. Cal Cohen, research director for the Community Research Initiative of New England. "These results support the use of phenotyping as a valuable scientific tool."

HIV can develop resistance to any of the 14 drugs currently available to treat the condition; this is a major reason for treatment failure. The study enrolled 273 patients who had failed to respond to first-line therapy using a combination of drugs, including at least two nucleoside analogue reverse transcriptase inhibitors and a protease inhibitor. The patients were randomized to receive therapy based on phenotypic testing or on treatment history alone (standard of care) and were observed for 16 weeks following treatment change.

The study showed that those using resistance testing experienced a significantly greater drop in viral load, and a greater proportion had a reduction in viral load to undetectable levels. The number of active drugs - drugs to which the patients' virus was still sensitive - was much greater for those whose treatment was guided by resistance testing.

The study was conducted in collaboration with 25 leading AIDS treatment centers and Glaxo Wellcome. Virco, located in the U.S., Belgium, United Kingdom and Ireland, is the only company to provide both genotyping and phenotyping HIV drug resistance testing. For more information, surf to www.vircolab.com.

DAPD in HIV-infected patients

Triangle Pharmaceuticals Inc. presented data on the antiviral activity of nucleoside analogue DAPD in HIV-infected patients who have failed multiple antiviral drugs. The researchers presented two reports: an analysis of the drug candidate's activity in vitro against resistant strains of HIV-1 and HBV, and results from a short-term, Phase I/II clinical trial of DAPD monotherapy treatment of multi-drug failure HIV infected patients.

In the laboratory studies, DAPD was active against AZT, 3TC, and multi-drug resistant HIV isolates. The drug candidate also was active against 3TC and famciclovir resistant HBV isolates in vitro.

In the Phase I/II clinical trial, 20 treatment-experienced patients received oral doses of 200mg, 300mg, or 500mg twice daily of DAPD as a monotherapy. These patients had previously failed an average of seven antiretroviral drugs.

"Proof of antiviral activity in patients who have failed multiple drugs is especially encouraging and confirms the data," said Dr. Franck S. Rousseau, chief medical officer of Triangle Pharmaceuticals. "We are extremely enthused by these data and look forward to the initiation of additional studies in combination therapy later this year."

Triangle Pharmaceuticals Inc. is a specialty pharmaceutical company engaged in the development of new antiviral drug candidates, with particular focus on therapies for HIV, hepatitis B, and hepatitis C. Triangle also is developing other immunotherapies for HIV. More information is available at www.tripharm.com.

CEL-SCI's collaboration with NCI

CEL-SCI Corporation announced a cooperative research and development agreement with the National Cancer Institute to jointly test NCI's HIV peptide epitopes and CEL-SCI's L.E.A.P.S. (Ligand Epitope Antigen Presentation System) platform technology for peptide delivery. The goal of the collaboration with NCI is to develop an improved HIV vaccine. The agreement marks the eighth collaboration with a major research group by CEL-SCI for its L.E.A.P.S. technology.

Geert Kersten, CEO of CEL-SCI, said their "objective is to find the best research teams for certain diseases and to collaborate with them. The ultimate goal is to quickly and cost-effectively advance new therapeutic vaccine candidates into human studies."

The L.E.A.P.S. technology is also the subject of ongoing collaborations at Johns Hopkins University, the U.S. Naval Medical Research Center, the University of Maryland, and the University of Nebraska Medical Center. CEL-SCI Corp. is a biopharmaceutical company that identifies, develops, and commercializes products to mobilize the immune system. For more information, go to www.cel-sci.com.

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