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About CAHCLS Home Page What We Do From the President Executive Members 2008 Meeting Date and Place Registration Agenda 2007 Meeting Agenda Minutes 2006 Meeting Agenda Minutes 2005 Meeting Agenda Minutes Links Last Updated July 31, 2006	National HIV Drug Resistance (Genotyping) External Quality Assessment Program by Dr. John Kim The introduction of new anti-retroviral therapies has resulted in tremendous advances in the treatment of those infected with Human Immunodeficiency Virus (HIV). However as with most drug therapies the development of resistance to these drugs is a reality and remains a major reason for treatment failure. While viral load measurements are useful as indirect tools in measuring the emergence of drug resistance, these tests cannot directly determine if drugs resistant mutations are present. There are two general approaches used to measure HIV drug resistance: (a) phenotyping is a direct measure of resistance which tests the level of sensitivity of a patient’s HIV to particular drugs in cell culture. These tests however are time consuming and costly and are only performed in specialized labs and (b) genotyping, which uses DNA sequencing to determine if specific genetic mutations are responsible for drug failure. In general genotypic assays are considered to be more valuable in determining drug failure rather than drug success. There are several methods of performing DNA genotyping for the drug resistance including both commercial and in-house methods. The DNA sequence that is obtained is compared against one of several interpretative tables or algorithms. These algorithms contain lists of mutations that are directly associated with the development of drug resistance. In the summer of 2002 at the annual meeting of HIV Clinical Lab Testing meeting, a consensus was reached that supported the development and implementation of a quality control/proficiency testing program for labs intending to use DNA genotyping in the clinical care management of HIV-infected persons. This program was subsequently developed by the National HIV/AIDS and Retrovirology Laboratories of Health Canada and the British Columbia Center for Excellence in HIV/AIDS. The first panel in this program was sent to participants in November, 2002. The goal of this panel was to first examine the quality of DNA sequencing prior to addressing differences in drug resistance algorithms. One interesting finding from this panel highlighted the importance of data management prior to sequence submission (see report). The second panel was shipped in November 2003, this time with the goal of examining differences in HIV testing algorithms used by Canadian labs. The final report from this panel was not ready at the time of this article submission but a review of the data showed an extremely high correlation in the quality of the DNA sequence obtained by participating labs. This is encouraging as it implies that any differences in the ‘final’ drug resistance profile will most likely not be due to poor quality DNA sequences and instead will be due to differences in the interpretative algorithms used. The implementation of DNA genotyping is still in its early stages. However, initial findings from this program already indicate that the quality of DNA sequencing obtained within labs involved in HIV clinical care management is extremely high and that HIV infected Canadians will receive the highest level of care possible with this new technology. For further information on: (a) this program please contact: Dr. John Kim Chief-National Laboratory for HIV Reference Services CIPDC PL 0603A Tunney’s Pasture tel: (613) 957-9666 Ottawa, Ontario fax: (613) 957-1163 K1A 0L2 Rick Galli Coordinator-HIV Resistance Testing BC Centre for Excellence in HIV/AIDS 613-1081 Burrard St. Vancouver, BC tel: (604)-806-9145 V6Z 1Y6 (b) DNA genotyping (general) – HIV_Drug_Resistance_No_Nonsense_Guide.pdf (c) copy of the first report – DR.A-02_report.report.May.2003.FINAL.pdf The above two reports are in Adobe .pdf file. To read this file format, you need Adobe Reader, click on the button on the right for a free download. March 04, 2004
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