Primary HIV-1 drug resistance in Canada:

Updated results from the Canadian HIV Strain and Drug

Resistance Surveillance Program

Canadian HIV Strain and Drug Resistance Surveillance Program

XVI International AIDS Conference

Toronto

August 13-18

Canadian HIV SDR Program Partners and Contributing Authors

PHAC BC AB

Chris Archibald Michael Rekart Ameeta Singh

Gaya Jayaraman Jutta Preiksaitis

Neil Goedhuis SK

Paul Sandstrom Huiming Yang MB

James Brooks Fred Sidaway Magdy Dawood

Harriet Merks Greg Hammond

ON

NS Robert Remis NL

Maureen Baikie Carole Swantee Sam Ratnam

Faith Stratton

Acknowledgments

Field Surveillance Officers, PHAC

Elsie Wong (BC)Sabrina Plitt (AB)Erin Laing (SK)Michelyn Woods (MB)Lena Shah (ON)Tracey MacDonald (NS)

HIV Surveillance Section, PHACJennifer PennockJennifer GeduldChris SheardownStéphane Racette

Objectives

• To describe the prevalence of primary drug resistance in Canada and associated trends (1998-2005)

• To describe the factors associated with primary drug resistance

Background – HIV Drug Resistance

• Drug resistance among untreated individuals (primary DR) is presumably due to transmission of a drug resistant strain of HIV from a treated individual

• Prior to the Canadian HIV SDR program no systematic surveillance for primary DR across Canada

Program Description

• Comprises all individuals newly diagnosed with HIV in Canada for whom left-over diagnostic serum samples are available for subtype and DR genotyping.

• No subjects are directly recruited

• Only treatment-naïve individuals are included

SDR Surveillance Program-Participating Provinces

BC AB

SK

MB

NL

ONNS

Data Collection and Transfer

P/T Partners

SRAD

PHAC

National HIV Laboratories

Laboratory resultsplus Epidemiological data

Serum specimens

Epidemiological data => Routine + Enhanced

subtype data

primary DR mutations

“detuned” assay data

PI2.1%

NNRTI2.0%NRTI

3.9%

MDR1.1%

WT90.9%

N = 2,333

Distribution of Primary DR1998-2005

0

10

20

30

40

50

60

70

M41

L

T21

5C/D

/E/S

/I/L

L210

W

M18

4V

V11

8I

T21

5Y

T69

D

D67

N

K21

9Q

Q15

1M

A62

V

K65

R

F77

L

V75

I

M18

4I

Y11

5F

F11

6Y

K10

3N

V10

8I

G19

0A

Y18

1C

Y18

8L

G19

0S

P22

5H

L100

I

Y18

1I

M23

0L

P23

6L

L90M

M46

I

M46

L

D30

N

V82

F

I84V

V82

A

G48

V

PI NNRTI NRTI

Nu

mb

er

Ca

se

s w

ith

Mu

tati

on

Mutations Associated with DR

PI NRTINNRTI

Proportion of cases with primary DR (overall), 1998-2005

p=0.056

0

2

4

6

8

10

12

1998 1999 2000 2001 2002 2003 2004 2005

Year of Diagnosis

p=0.003

Proportion of cases with resistance to NNRTI 1998-2005

Pro

port

ion

with

Dru

g R

esis

tanc

e (%

)

Variable Sample size% Drug

Resistant p value

Sex 0.329

Male 1701 8.8

Female 619 10.2

Risk Exposure 0.951

MSM 662 9.4

MSM/IDU 71 8.5

IDU 637 8.6

Heterosexual 685 9.2

Age 0.822

15-19 36 13.9

20-29 491 9.4

30-39 852 9.9

40-49 639 8.0

50-59 207 8.7

60+ 83 8.4

Factors associated with primary DR

VariableSample

size% Drug

Resistantp value

Time of Infection 0.130

Recent 538 10.4

Established 1421 8.2

Ethnicity 0.052

Aboriginal 550 11.1

Asian 79 8.9

Caucasian 1200 8.3

African/Caribbean 222 4.5

Subtype 0.012

B 2040 9.7

non-B 288 5.2

Factors associated with primary DR, con’t

Published August, 2006 (contains data to March 2005)

Data from SDR program generate research questions and used for other specific analyses

August 2006

Program Limitations

• Data only include individuals who were infected and diagnosed with HIV.

• Results based on number of newly diagnosed cases with sufficient sera for whom PCR amplification was successful.

• Treatment history cannot always be verified.• Current assays may not accurately identify

recent infections particularly among the non-B subtypes.

Conclusions• Prevalence of primary DR in sample 9.1%.

• Overall prevalence of primary DR may be increasing over time; accounted for mainly by an increase in the prevalence of NNRTIs.

• No significant differences found by sex, age at diagnosis or across exposure category

• Higher proportion of primary drug resistance found among:– Recent infections– Ethnicities other than African/Caribbean– B subtypes

Next Steps• Increase coverage across Canada to increase

representativeness, sample size and power • Liaise with national stakeholders to inform

prevention and treatment programs and policies• Partner with national and international experts to

develop list of mutations to be used for DR surveillance in B and non-B subtypes

• Partner with international experts to monitor global trends