Transcript 12 Fairbairn_ARTresist_RMACP_Nov2012

Baseline Antiretroviral Resistance Testing
among HIV-Positive Injection Drug Users
in a Canadian Setting
Nadia Fairbairn1
M-J Milloy1
Thomas Kerr1, 2
Richard Harrigan1, 2
Silvia Guillemi1, 2
Robert Hogg1, 2
Julio Montaner1, 2
Evan Wood1, 2
1 BC
Centre for Excellence in HIV/AIDS
2 Department of Medicine, University of British Columbia
Disclosures
• No affiliations or conflicts of interest
Background
• Personalized medicine uses individual patient
characteristics to improve therapeutic outcomes
Canadian Institutes of Health Research, 2012
Background
• HIV a leader in the field of personalized medicine
with medications tailored to the human and viral
genomes (Cheng, Carbonell & Macarthur, 2010)
• HLA pre-testing for Abacavir hypersensitivity
reaction
• Tailoring antiretroviral therapy (ART) based on
patterns of drug resistance
Background
• Antiretroviral drug resistance is known to emerge
with inadequate adherence to ART (Bangsberg et al,
2001)
• HIV-resistant strains can be transmitted from one
person to another
• Antiretroviral resistance testing important prior to
initiating therapy and in the setting of virologic
failure on ART
Summary of situations in which
resistance testing is recommended
Hirsch M S et al. Clin Infect Dis. 2003;37:113-128
Background
• HIV-positive injection drug users demonstrate:
• Lower levels of ART adherence (Palepu et al., 2003)
• Higher rates RNA viral load (Rodriguez-Artenez et al., 2006)
• Higher rates ART discontinuation (Malta et al., 2008)
• Antiretroviral therapy withheld from HIV-positive
IDU over concerns of ART drug resistance (Werb et
al., 2010)
• Not much known about the patterns of ART
resistance testing among HIV-positive IDU
Objective
• Examine patterns of resistance testing
among a cohort of injection drug users and
factors associated with baseline ART
resistance testing in a Canadian setting
Methods
• The ACCESS cohort is an ongoing prospective
cohort of HIV-positive individuals who inject drugs
• Participants recruited through self-referral and
street outreach from Vancouver’s Downtown
Eastside since 1996
• At baseline and semi-annually participants provide
blood sample and complete questionnaire
Methods
• Primary outcome of interest: antiretroviral
resistance testing prior to initiation of ART
• Variables:




Gender, age, ethnicity
Physician experience
Baseline viral load (per log10)
Baseline CD4 cell count (per 100 cells/mm3)
• Multivariate logistic regression model fit using an a
priori defined model-building approach
Results
• Sample characteristics (n=854):
 595 (70.0%) ART-naïve participants initiated therapy
 231 (39.1%) female respondents
 229 (38.5%) Aboriginal ancestry
• Primary outcome of interest:
Did the participant undergo ART resistance testing prior to treatment?
 Yes

 No
ACCESS Cohort who accessed ART (n=595)
Yes
No
56.5%
259 (43.5%)
Underwent ART
resistance testing
prior to initiation of
ART.
The proportion of individuals who had > 1 resistance test prior
to initiation ART 1996-2010
100
90
80
70
60
50
40
30
20
10
0
1995
1996
1997
1998
1999
2000
2001
2002
2003
2004
2005
2006
2007
2008
2009
2010
Multivariate logistic regression analysis of factors independently
associated with > 1 viral resistance test pre-ART initiation
• Multivariate Logistic Regression analyses
Adjusted** Odds Ratio
(95% CIs)
Aboriginal ancestry
Baseline ART
resistance test
Year of ART
initiation
Plasma HIV-1 RNA*
0.57
(0.39 – 0.83)
p < 0.001
1.25
(0.19 – 1.31)
p < 0.001
1.48
(1.20 – 1.83)
p < 0.001
* Time invariant, observed at baseline
** Model was also adjusted for age, gender, CD4 count & physician experience
Interpretations
• Significant increase in antiretroviral resistance
testing 1996 – 2010
• Aboriginal ancestry negatively associated with
baseline ART resistance testing
• Aboriginal ancestry 50% less likely to receive
baseline testing after adjusting for viral load and
year of ART initiation
Interpretations
• Multiple structural barriers to wellness faced by
people of Aboriginal ethnicity (Royal Commission on
Aboriginal Peoples, 1996)
• Slower uptake of ART and disproportionate number
never access treatment (Wood et al., 2006)
• Urgent need for culturally sensitive
interventions to address inequities in HIV care
for this population
Limitations
• Sample not randomly selected, findings may not
generalize to other IDU
• Relationships between explanatory variable and
outcome of interest may be subject to unobserved
confounding
• Further research needed to examine barriers to
testing in developing regions where ART is
expected to increase
Conclusion
• Levels of resistance testing have
significantly increased in accordance with
guidelines
• Individuals of Aboriginal ethnicity continue to
experience lower rates of resistance testing
• Careful attention must be paid to delivering
health care consistent with guidelines
Acknowledgements
• ACCESS participants
• ACCESS investigators and staff: Deborah
Graham, Peter Vann, Caitlin Johnston, Steve Kain,
and Calvin Lai
• US National Institutes of Health