1. Primary HIV Drug Resistance Surveillance in Canada
Surveillance and Risk Assessment Division &
National HIV and Retrovirology Laboratories,
Public Health Agency of Canada
and
Participating Provinces and Territories

2. Canadian HIV SDR Program Partners
Pubic Health Agency
Of Canada (PHAC) British Columbia Manitoba
Chris Archibald Michael Rekart Magdy Dawood
Marianna Ofner Mel Krajden Valerie Mann
Jocelyne Galloway Mark Gilbert Greg Hammond (ret)
James Brooks
Paul Sandstrom Saskatchewan Alberta
Harriet Merks Huiming Yang Ameeta Singh
Richard Pilon Fred Sidaway Jutta Preiksaitis
Mark Vanderkloot
Ping Yan Ontario Nova Scotia
Carol Swantee Maureen Baikie
Robert Remis Robert Strang
I’d like to thank our provinical collaborators and fellow Public Health Agency of Canada staff

3. Field Surveillance Officers, PHAC
Elsie Wong (British Columbia)
Sabrina Plitt (Alberta)
Erin Laing (Saskatchewan)
Michelyn Wood (Manitoba)
Claudia Rank (Ontario) Tracey MacDonald (Nova Scotia)
HIV Surveillance Section, PHAC
Jenni Vick
Kristina Lalonde
Stéphane Racette
Plus our Field Surveillance Officers located within the specific participating provinces and the Agencies HIV surveillance section

4. Highly Active Antiretroviral Therapy for HIV
Introduction of highly active antiretroviral therapy (HAART) for HIV changed the HIV landscape
Morbidity and mortality have decreased
The widespread use of HAART, along with continuing HIV incidence, results in the potential for transmission of drug-resistant viruses
Drug resistance in untreated individuals is primary drug resistance and is due to transmission of DR strain from treated individuals
-over the past 10 years, the world has witnessed one of the MOST significant chronic disease INTERVENTIONS ever seen – that of highly active antiretroviral therapy (HAART) for HIV infection.
-morbidity and mortality have plummeted in Canada and other areas of the world where there is unrestricted access to these drugs…..and HIV/AIDS has transformed from almost certain death to, at least for those receiving treatment, a long-term, manageable disease, with a potentially normal life expectancy.
According to recent National HIV prevalence and incidence estimates, there were an estimated people in Canada living with HIV as of the year 2005, with approximately 2500 new cases being reported to the National HIV surveillance system annually.
In conjunction with the widespread use of HAART, this can lead to the transmission of drug-resistant virus from individuals under treatment.

5. Secondary versus Primary (Transmitted) Drug Resistance
Failing Therapy Rx
Secondary DR Rx
HIV+ person not on treatment
HIV Drug resistance comes about in 2 ways. Secondary drug resistance comes about as a result of treatment therapy
Primary resistance comes about through the transmission of the HIV resistant virus to another person.
The monitoring and prevention of primary drug resistance is a public health issue in which prevention and early identification become essential interventions.
Primary DR WT
Wild Type Virus
Drug Resistant Virus

6. Goals of the Canadian HIV Strain and Drug Resistance Program
Improve HIV diagnostics and screening strategies for circulating strains
Inform vaccine development
Assess genetic markers for anti-retroviral drug resistance among newly diagnosed, treatment-naïve individuals
Assess HIV transmission patterns
The Canadian HIV Strain and Drug Resistance Surveillance program was set up with a number of goals and research objectives in mind.
We wanted to improve HIV diagnostics and screening strategies to detect all circulating strains of HIV in Canada.
It is believed that when developed, an HIV vaccine will likely be strain specific. As such, having an understanding of the strains circulating in Canada will also inform vaccine development programs.
Performing drug resistance testing through this program will enable us to assess the genetic markers for antiretroviral drug resistance among newly diagnosed, treatment naïve individuals.
Finally, we are able to assess the transmission patterns of HIV, its pathogenesis, and the progression of HIV-related diseases.

7. Sampling methods
Population-based study comprising all individuals newly diagnosed with HIV for whom left-over diagnostic serum samples are available
No subjects are directly recruited
Only first-time positive, treatment-naïve individuals are included

8. plus epidemiological data
Data Collection and Transfer
National HIV
Laboratories
Serum specimens
Epidemiological data
subtype data
Provincial
Partners
PHAC
primary DR mutations
“detuned” assay data
laboratory results
plus epidemiological data
Surveillance
Division

10. Results

11. HIV Drug Resistance in Canada 1996-2005 (N=2703*)
Wild Type 90.6%
Drug Resistance 9.4%
(1 case since 1996)
*Results of 4 western provinces

12. Mutations Associated with DR
This looks like a pretty overwhelming slide, but the important thing to take away is the variety and range of mutations that are responsible for drug resistance. This list is constantly being revised as new information becomes available. The mutations shown here are not mutually exclusive, so there is some overlap in the counts shown here for the 1% of cases that have a multi-drug resistance profile.
Information sources on resistance include: IAS-USA and Stanford Databases.
NRTI
NNRTI PI

13. Characteristics of individuals with primary drug resistant HIV-1
Looking at some of the key variables collected, this table displays the rates of drug resistance.
Among male cases, 9% of specimens had mutations associated with primary drug resistance. Similar to females at 9.8%.
The mean age of those with primary DR was 37, standard deviation of 10.6 yrs.
The highest proportion of cases with primary drug resistance was found among aboriginal cases (10.8%), with the lowest among African/ Caribbean cases (5.6%)
None of these variables were found to be significant
9,6% of those found to be subtype B had primary DR while only 5.8% of non-B subtypes, which demonstrates a statistically significant difference. The B subtype is the primary circulating strain in Canada.

14. Characteristics of individuals with primary drug resistant HIV-1
Looking at exposure category and year of diagnosis, while there were some slight differences noted between groups, however these were not found to be statistically significant.
For detuned results the results (recent vs. established) were not associated with year of diagnosis (p=0.21)
When comparing infections identified as recent through the detuned assay, there was a significantly higher proportion of Drug Resistance than was found among established infections.
Note: Year 2005 was removed from analysis of year of diagnosis due to incomplete data from BC and Alberta, we are awaiting the samples from Alberta and the BC samples we have but no results yet.

15. Primary HIV DR in Canada, % by drug class and year
1997 had ZERO DR in each category. All were WT strains.

16. Trends in primary DR over time
1999
2000
2001
2002
2003
2004
2005
0.05
0.10
0.15
0.20
0.25
0.30
For some other provinces
For some provinces
Proportion of resistance
to any drug
1998
1999
2000
2001
2002
2003
2004
2005
0.02
0.04
0.06
0.08
0.10
0.12
NRTI*
PI*
NNRTI*
Resistance to certain drug classes
Overall trend after year 2000, there is no statistical significance to suggest a departure from a constant time-trend, but there is evidence of preliminary trends for certain drug classes
While there was no clear overall increase in the proportion of drug resistance over time, recent modelling work has shown that there is evidence of difference between the drug classes, with a decrease in resistance to NRTIs over time, a peak and drop off in resistance to protease inhibitors, and an increase in resistance to NNRTIs.

17. Discussion
9.4% of newly diagnosed HIV cases have primary DR and no indication that this is changing recently
trends are seen for certain drug classes
virtually no triple-drug resistance in Canada (only 1 case recorded)
Primary DR most common in:
subtype B infection: may indicate differential access to treatment
recently infected cases: may indicate not all mutations are persistent
-some changes for individual drug classes have been seen
-the trends by drug class have declined in NRTI, increased in NNRTI and there is no change in PI

18. Public Health Implications
Data on prevalence of primary drug resistance can be used to develop population recommendations for initial treatment (especially for pregnant women and situations of post-exposure prophylaxis)
Extent of transmitted drug-resistance can serve as an indicator to help evaluate the effectiveness of prevention programs

19. Future directions
Continue to improve representativeness of program in Canada
Expand analysis of data:
- examine mutation distributions by HIV-1 subtype
- use the detuned testing data to monitor trends and associated characteristics of the new diagnoses that are recent infections
Encourage public health use of data
Maintain and expand collaboration with international partners