1. Baseline Antiretroviral Resistance Testing among HIV-Positive Injection Drug Users in a Canadian Setting Nadia Fairbairn 1 M-J Milloy 1 Thomas Kerr 1, 2 Richard Harrigan 1, 2 Silvia Guillemi 1, 2 Robert Hogg 1, 2 Julio Montaner 1, 2 Evan Wood 1, 2 1 BC Centre for Excellence in HIV/AIDS 2 Department of Medicine, University of British Columbia

2. No affiliations or conflicts of interestNo affiliations or conflicts of interest Disclosures

3. Personalized medicine uses individual patient characteristics to improve therapeutic outcomesPersonalized medicine uses individual patient characteristics to improve therapeutic outcomes Background Canadian Institutes of Health Research, 2012

4. HIV a leader in the field of personalized medicine with medications tailored to the human and viral genomes (Cheng, Carbonell & Macarthur, 2010)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 reactionHLA pre-testing for Abacavir hypersensitivity reaction Tailoring antiretroviral therapy (ART) based on patterns of drug resistanceTailoring antiretroviral therapy (ART) based on patterns of drug resistance Background

5. Antiretroviral drug resistance is known to emerge with inadequate adherence to ART (Bangsberg et al, 2001)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 anotherHIV-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 ARTAntiretroviral resistance testing important prior to initiating therapy and in the setting of virologic failure on ART Background

6. Summary of situations in which resistance testing is recommended Hirsch M S et al. Clin Infect Dis. 2003;37:113-128

7. HIV-positive injection drug users demonstrate:HIV-positive injection drug users demonstrate: Lower levels of ART adherence (Palepu et al., 2003)Lower levels of ART adherence (Palepu et al., 2003) Higher rates RNA viral load (Rodriguez-Artenez et al., 2006)Higher rates RNA viral load (Rodriguez-Artenez et al., 2006) Higher rates ART discontinuation (Malta et al., 2008)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)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 IDUNot much known about the patterns of ART resistance testing among HIV-positive IDU Background

8. Objective Examine patterns of resistance testing among a cohort of injection drug users and factors associated with baseline ART resistance testing in a Canadian settingExamine patterns of resistance testing among a cohort of injection drug users and factors associated with baseline ART resistance testing in a Canadian setting

9. Methods The ACCESS cohort is an ongoing prospective cohort of HIV-positive individuals who inject drugsThe 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 1996Participants 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 questionnaireAt baseline and semi-annually participants provide blood sample and complete questionnaire

10. Methods Primary outcome of interest: antiretroviral resistance testing prior to initiation of ARTPrimary outcome of interest: antiretroviral resistance testing prior to initiation of ART Variables:Variables: Gender, age, ethnicity Gender, age, ethnicity Physician experience Physician experience Baseline viral load (per log 10 ) Baseline viral load (per log 10 ) Baseline CD4 cell count (per 100 cells/mm 3 ) Baseline CD4 cell count (per 100 cells/mm 3 ) Multivariate logistic regression model fit using an a priori defined model-building approachMultivariate logistic regression model fit using an a priori defined model-building approach

11. Did the participant undergo ART resistance testing prior to treatment?  Yes  No Results Sample characteristics (n=854):Sample characteristics (n=854): 595 (70.0%) ART-naïve participants initiated therapy 595 (70.0%) ART-naïve participants initiated therapy 231 (39.1%) female respondents 231 (39.1%) female respondents 229 (38.5%) Aboriginal ancestry 229 (38.5%) Aboriginal ancestry 259 (43.5%) Underwent ART resistance testing prior to initiation of ART. ACCESS Cohort who accessed ART (n=595) Primary outcome of interest:Primary outcome of interest:

12. The proportion of individuals who had > 1 resistance test prior to initiation ART 1996-2010

13. Baseline ART resistance test Baseline ART resistance test Year of ART initiation 1.25 (0.19 – 1.31) p < 0.001 Adjusted** Odds Ratio (95% CIs) Aboriginal ancestry 0.57 (0.39 – 0.83) p < 0.001 Plasma HIV-1 RNA* * Time invariant, observed at baseline ** Model was also adjusted for age, gender, CD4 count & physician experience Multivariate Logistic Regression analysesMultivariate Logistic Regression analyses 1.48 (1.20 – 1.83) p < 0.001 Multivariate logistic regression analysis of factors independently associated with > 1 viral resistance test pre-ART initiation

14. Interpretations Significant increase in antiretroviral resistance testing 1996 – 2010Significant increase in antiretroviral resistance testing 1996 – 2010 Aboriginal ancestry negatively associated with baseline ART resistance testingAboriginal 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 initiationAboriginal ancestry 50% less likely to receive baseline testing after adjusting for viral load and year of ART initiation

15. Interpretations Multiple structural barriers to wellness faced by people of Aboriginal ethnicityMultiple 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 treatmentSlower 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 populationUrgent need for culturally sensitive interventions to address inequities in HIV care for this population

16. Limitations Sample not randomly selected, findings may not generalize to other IDUSample not randomly selected, findings may not generalize to other IDU Relationships between explanatory variable and outcome of interest may be subject to unobserved confoundingRelationships 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 increaseFurther research needed to examine barriers to testing in developing regions where ART is expected to increase

17. Conclusion Levels of resistance testing have significantly increased in accordance with guidelinesLevels of resistance testing have significantly increased in accordance with guidelines Individuals of Aboriginal ethnicity continue to experience lower rates of resistance testingIndividuals of Aboriginal ethnicity continue to experience lower rates of resistance testing Careful attention must be paid to delivering health care consistent with guidelinesCareful attention must be paid to delivering health care consistent with guidelines

18. Acknowledgements ACCESS participantsACCESS participants ACCESS investigators and staff:ACCESS investigators and staff: Deborah Graham, Peter Vann, Caitlin Johnston, Steve Kain, and Calvin Lai US National Institutes of Health