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British Columbia Funds C$5M HIV Clinical Sequencing Project

NEW YORK (GenomeWeb News) – A team of clinical researchers in Vancouver has received C$5 million (US$4.8 million) in new funding to use next-generation sequencing to improve methods for testing for drug resistance in HIV/AIDS patients, Genome British Columbia said today.

The effort, led by Richard Harrigan, head of genomics research at the BC Centre of Excellence in HIV/AIDS at St. Paul's Hospital in Vancouver, will seek to improve upon previous methods for detecting drug resistance, develop drug-resistance surveillance tools, and devise methods for basing treatment strategies on each patient's own genomic information.

The project is being funded by Genome BC; Genome Canada; Genome Quebec; the Canadian Institutes of Health Research; ViiV Healthcare; and the St. Paul's Hospital Foundation.

Harrigan told GenomeWeb Daily News today that resistance testing has been a part of HIV treatment for about a decade, but the development of new classes of drugs has required the co-development of Sanger-based sequencing tests for each new drug. What he and his partners are working on is combining all of the current Sanger-based tests into one test, for which they will be using Illumina's MiSeq-based sequencing.

"So, instead of having every [HIV patient] take four or five tests, we just will automatically give everybody one test," said Harrigan. "That is not only more convenient, it also means that in this one test we will have more sensitivity to detect low levels of drug-resistant variants that would have been missed by the older methods."

He said the St. Paul's Hospital team engages in a "double pharmacogenetics" approach, which involves sequencing the virus and the patient.

Harrigan explained that his team conducts the sequencing before patients receive a therapeutic regimen, just in case a patient was infected with a drug-resistant virus. They also tests the patient for the HLA-B*57:01 variant, which indicates that a patient will have an adverse reaction to a commonly used HIV drug.

He said his group also will look for additional markers for adverse side effects in the patients, based on sequencing analyses.

The tests they plan to employ have already been developed, he said, but now his group will use the MiSeq to serve as a fixed technology to validate that these tests really work.

"Truly validating [such tests] takes a lot of effort, because we need valid clinical outcome data," Harrigan said, noting that his group already has such data in hand, which it now plans to analyze.

They also are looking at both the virus and human genetics to discover more markers that could be used to develop more advanced tests in the future.

The biggest benefit of using next-gen sequencing in viral drug-resistance testing is the level of specificity it provides, said Harrigan. Such increased specificity could help physicians avoid a situation where someone is cleared as not having a drug-resistant virus when they actually do, and then prescribing treatment with incorrect information.

Harrigan also said that his group plans to share their methods with researchers in other countries with the aim of spreading their findings and helping patients beyond British Columbia.