HIV-1 Strain and Primary Drug Resistance in Canada
Surveillance Report to June 30, 2002

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Technical Notes

Data collection and reporting

The results presented here represent individuals who sought testing, whose condition was properly diagnosed, and whose results were reported to provincial health authorities and Health Canada. Furthermore, they include only those individuals for whom sufficient sera, taken for the purposes of diagnostic testing, were available to send to the national HIV laboratories and, of these, the subset for whom subtype analysis and/or primary drug resistance genotyping was completed as of June 30, 2002. The quality of samples that are received by the national HIV laboratories also determines whether subtype and primary drug resistance results can be generated. Typically, the laboratories make at least two attempts on samples that are difficult to amplify with the in-house and consensus group M primers. The National Laboratory for HIV Genetics is currently in the process of examining the use of other primer sets for RT-PCR amplification.

The epidemiologic data collected through the CHSDRSP consist of information routinely collected on the national or provincial HIV case reporting forms plus additional data that allow interpretation of the laboratory results. These additional data include type of laboratory specimen sent, date of last negative HIV test, history of seroconversion (if any), antiretroviral treatment history (if any) and viral load count at diagnosis. These enhanced data are usually collected when the affected individual seeks treatment. Not all individuals with a diagnosis of HIV seek treatment; furthermore, linkages with clinical databases may not be feasible to collect these data.

The quality and completeness of epidemiologic data remain problematic (see Data Limitations section), and one of the key roles of federal field surveillance officers is to work with the provincial and territorial health partners to facilitate the collection and timely reporting of these data to Health Canada.

Exposure category hierarchy

HIV cases were assigned to a single exposure category according to an agreed-upon hierarchy of risk factors. The hierarchy is described in more detail in the HIV and AIDS in Canada Surveillance Report, available by contacting the Division of HIV/AIDS Epidemiology and Surveillance or electronically at http://www.phac-aspc.gc.ca/aids-sida/publication/index.html

Analysis of drug resistance

While both genotypic and phenotypic testing methods are well established, each has its limitations. Both tests provide information only on the virus that predominates at the time of sampling and are unable to identify virus that may be present as a result of previous drug exposures or that is present in “quasi” or minority species. This latter point is particularly important, as minority species of virus may become predominant under selective drug pressures that do not completely inhibit viral replication. Both assays are technically difficult to perform when the concentration of virus is < 1,000 copies/mL and may require highly specialized laboratory facilities and personnel. The ability of both assays to quantify resistance to certain drugs has not yet been determined. Phenotypic testing is expensive, at a cost of about US$800/test. With genotypic testing, repeat analyses may be required since mutations strongly associated with drug resistance continue to be “discovered”, and their complex interactions are only now beginning to be understood. For this reason, the list of mutations associated with  drug  resistance  is  updated  annually. The  analyses  that  are  presented  in  this  report  are based on the list of mutations shown in Appendix 2.

Interpretation of drug resistance

The interpretation of genotypic and phenotypic test results for patient care is still uncertain and under active research. The complexity of this task is compounded by several factors: genotypic and phenotypic test results may not correlate with one another; clinical relevance varies from drug to drug; the concentrations at which a drug is ineffective has not been determined in vivo; and the extent to which pharmaceutical interactions influence resistance is not well known. It is anticipated that the list of mutations on which the present results are based will change as new information on drug resistance mutations becomes available over time. International expert review panels meet periodically to review the latest laboratory and clinical findings in the development of guidelines for interpreting genotypic and phenotypic drug resistance mutations for clinical management. A similar panel of national experts to advise the CHSDRSP on drug resistant mutations and their interpretation is being assembled.

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