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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
Canadian HIV SDR Program Partners
Pubic Health Agency
Of Canada (PHAC)
Chris Archibald
Marianna Ofner
Jocelyne Galloway
James Brooks
Paul Sandstrom
Harriet Merks
Richard Pilon
Mark Vanderkloot
Ping Yan
British Columbia
Michael Rekart
Mel Krajden
Mark Gilbert
Manitoba
Magdy Dawood
Valerie Mann
Greg Hammond (ret)
Saskatchewan
Huiming Yang
Fred Sidaway
Alberta
Ameeta Singh
Jutta Preiksaitis
Ontario
Carol Swantee
Robert Remis
Nova Scotia
Maureen Baikie
Robert Strang
 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
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
Secondary versus Primary (Transmitted)
Drug Resistance
Failing
Therapy
Rx
Secondary
DR
HIV+ person
not on
treatment
WT
Primary
DR
Wild Type Virus
Drug Resistant Virus
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, treatmentnaïve individuals
•
Assess HIV transmission patterns
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
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
http://www.phac-aspc.gc.ca/publicat/hiv1-vih1-05/index.html
Results
Type
%
HIV Drug Resistance in Canada
1996-2005 (N=2703*)
NRTI 3.9%
Wild Type 90.6%
Drug Resistance 9.4%
NNRTI 2.3%
PI 2.1%
Two-class 1.0%
Three-class 0.1%
(1 case since 1996)
*Results of 4 western provinces
0
M41L
T215C/E/D/S/L
L210W
M184V
K219Q
A62V
D67N
T215Y
T69D
K65R
K70R
Q151M
V118IV
F116Y
F77L
V75I
K103N
G190A
G190S
V108IV
Y181CY
Y188L
P225H
G190A/E
L100I
M230L
P236L
Y181I
L90M
M46I
M46L
I50V
G48V
M46IMR
V82FV
D30N
I84V
V82A
V82T
Mutations Associated with DR
120
100
80
60
40
20
NRTI
NRTI
NNRTI
NNRTI
PI
PI
Characteristics of individuals with
primary drug resistant HIV-1
Characteristics of individuals with primary
drug resistant HIV-1
Primary HIV DR in Canada,
% by drug class and year
Trends in primary DR over time
Proportion of resistance
to any drug
0.12
0.30
For some provinces
Resistance to certain drug classes
0.10
0.25
0.20
0.08
17
88
9
56
8
62
0.15
29
284
0.10
0.05
10
214
1999
4
51
17
128
26
175
0.06
NRTI*
NNRTI*
0.04
27
305
27
366
18
286
20
369
2000
17
116
0.02
PI*
For some other provinces
2001
2002
2003
2004
2005
1998
1999
2000
2001
2002
2003
2004
2005
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
recorded)
(only 1 case
• Primary DR most common in:
– subtype B infection: may indicate differential access to
treatment
– recently infected cases: may indicate not all mutations are
persistent
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
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