BioWorld International Correspondent

LONDON - A not-for-profit company called RDI Ltd. was launched to lead an international collaboration to use pharmacogenomics in combating HIV drug resistance and improving the treatment of patients with AIDS.

RDI (Resistance Response Database Initiative) will collect HIV genotype data from patients around the world to track the development of drug resistance in the virus and advise physicians on the best combination of drugs to treat individuals, depending on the strain of HIV with which they are infected.

Andrew Revell, CEO of RDI, told BioWorld International: "This is a new concept in international collaboration. No one hospital or clinic would have sufficient data to build a mathematical model like ours, which will tell physicians which combination of drugs to give patients, depending on the strain of HIV they are infected with.

"That's why we have set [RDI] up as not for profit: we want people to give the data for free, and we will make the findings freely available."

To date, funding has come from the National Institute of Allergy and Infectious Diseases, a division of the National Institutes of Health in Bethesda, Md., and RDI now is looking for further sponsors, including pharmaceutical and biotechnology companies.

The main reason for failing HIV treatment is that the virus readily develops resistance to antiretroviral drugs. HIV replication is highly error prone and mutations can make HIV less susceptible to one or more drugs.

In developed countries, HIV genotype testing often is used to help identify the drug combination that will overcome resistance in particular patients. But there are more than 200 known mutations that can affect drug resistance and an enormous number of drug combinations available.

"Generally the choice of drugs is made by individual clinicians using differing sets of rules, and there are a number of systems for interpreting what drugs should be administered," Revell said.

RDI intends to build a database that defines the relationship between changes in the genetic code of HIV and the response of patients to different drug combinations. Response is measured as the change in viral load after taking the drugs. RDI aims to collect genotyping, treatment and treatment responses from 10,000 patients.

"Once this data is assimilated, it should be possible to submit the genetic code of HIV from an individual patient and predict the best combination of drugs," Revell said.

At the end of January the company had data on 750 patients.

RDI also is looking for funding to carry out a survey of HIV strains in Africa. It is thought that resistance to antiretrovirals is more likely to develop there because patients do not have access to all available drugs, they may not be able to financially keep taking drugs for the longer term, and compliance is poor.

"If you are taking three or four drugs and they are suppressing the viral load, it is difficult for the virus to mutate," Revell said. "But if you take two drugs and then stop, that is the ideal situation for the virus to mutate."

RDI has the backing of several organizations, including the British Columbia Center for Excellence in HIV/AIDS in Vancouver, the U.S. Military HIV Research Group in Washington and HIV Monitoring Service at the University of Siena in Italy. Revell said he hopes to get backing from pharmaceutical and diagnostic companies that make AIDS drugs and HIV genotyping kits.

"I think when resistance was first identified, pharma companies didn't want to know about it," he said. "Now they recognize the best way to deal with resistance is to be on the cutting edge. They need to know the resistance profile of their drugs."