BC research team to develop drug resistance test, personalized treatment for HIV/AIDS

Builds on advances in genomics

Genome British Columbia is helping to fund an ambitious applied research project that its backers say could contribute to the eventual elimination of HIV/AIDS. The project will see the use of genomics to develop an improved drug-resistance test, an early warning system to monitor and map drug resistance and personalized drug treatment for patients based on their particular DNA profile.

The new test will be made available to all HIV patients in BC and the technology will be shared with laboratories worldwide, as is software that was developed from current testing methods.

The $5-million, four-year project is being undertaken by researchers at the BC Centre of Excellence in HIV/AIDS (BC-CfE) and is one of four BC-based genomics and personalized medicine proposals that were successful in the recent $150-million Large-Scale Applied Research Project competition staged by Genome Canada and the Canadian Institutes of Health Research (CIHR).

"We want to reduce the disease burden and reduce the number of viruses in people so it's less transmissible," says Dr Richard Harrigan, project leader, head of genomics research and director of the laboratory program at BC-CfE. "The funding is not just for new testing methodologies but for the socio-demographics of resistance. The project has at least three deliverables."

Since the formation of BC-CfE in 1992, there has been tremendous progress made in the fight against AIDS, with the introduction of several drugs to combat the disease and a 90% reduction in fatalities. Patients now routinely take a cocktail of antiretroviral drugs (HAART – highly active antiretroviral therapy) which was first introduced at the 1996 Vancouver International AIDS Conference.

But as resistance to certain antiretrovirals increases, researchers have been struggling to determine how best to match drug combinations to specific patients. Harrigan says BC and the BC-CfE offer an ideal environment for pursing personalized HIV treatment.

The project research team has:

• considerable experience developing and validating next-generation methods and their implementation,

• close links to users, guideline committees and policy makers,

• access to clinical samples with consents and matching longitudinal data allowing for validation of new tests from randomized Phase III clinical trials and province-wide registries.

"We a large, centralized facility that delivers all HIV drugs in the province so that we can link outcome data to test results," he says. "If drug resistance is high, we can choose other drugs and there are now a lot of options. The test tells us what drug you don't want to do and we can do this on the virus and human sides."

project holds potential for significant savings

Researchers project annual drug savings from the new resistance test could amount to $15,000 annually for each new HIV case that's avoided. Preventing 50 new HIV infections each year would save $11.25 million, not including other medical tests or lost productivity.

The HIV project is one of four successful proposals submitted by Genome BC to the Genome Canada/CIHR competition last March. Of the other three, two have been announced: personalized treatment of lymphoid cancer ($10 million) and reducing stroke burden with hospital-ready biomarker test for rapid TIA (mini-stroke) triage ($10 million).

The final project — clinical implementation and outcomes evaluation of blood-based biomarkers for management of chronic obstructive pulmonary disease (COPD) — will be officially announced in December.

For Genome BC, the four projects mark a significant turning point in what kinds of projects it funds and fits strategically with its current mandate.

The funding Genome BC has been able to leverage also meets the province's expectations of 3:1. To date, the BC government has provided Genome Canada with $85 million to execute its 2010-2015 strategic plan and is on target to support $340 million in new investments in the priority areas of life sciences, energy, mining, forestry and agriculture.

The HIC project exemplifies how Genome BC is moving research into the social and economic realms.

"We seem to have opportunities in BC in personalized health," says Genome BC?president and CEO, Dr Alan Winter. "This project is an area where the research is at a point where you can use genomics data to stratify patients and benefit the health system. It's not clinical translation yet but it's getting closer."

It's taken nearly 15 years, but the genomics research funded in Canada since the formation of Genome Canada and the six regional agencies is finally leading to actionable understanding of the mechanisms required before therapeutic interventions are made.

"All these areas (covered by the four projects) are advancing and how much the results can be used clinically depends on how tight the link is to genomics research," says Winter. "HIV is an area that's moving ahead and can now be used clinically (so) it's easier to explain (to policy and government people)."

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