Baseline Antiretroviral Resistance Baseline Antiretroviral Resistance Testing among HIV-Positive Testing among HIV-Positive

Injection Drug Users in a Canadian Injection Drug Users in a Canadian SettingSettingNadia FairbairnNadia Fairbairn11

M-J MilloyM-J Milloy11

Thomas KerrThomas Kerr1, 21, 2

Richard HarriganRichard Harrigan1, 21, 2

Silvia GuillemiSilvia Guillemi1, 21, 2

Robert HoggRobert Hogg1, 21, 2

Julio MontanerJulio Montaner1, 21, 2

Evan WoodEvan Wood1, 21, 2

1 1 BC Centre for Excellence in HIV/AIDSBC Centre for Excellence in HIV/AIDS2 2 Department of Medicine, University of British ColumbiaDepartment of Medicine, University of British Columbia

• No affiliations or conflicts of interestNo affiliations or conflicts of interest

DisclosuresDisclosures

• Personalized medicine uses individual Personalized medicine uses individual patient characteristics to improve patient characteristics to improve therapeutic outcomestherapeutic outcomes

BackgroundBackground

Canadian Institutes of Health Research, Canadian Institutes of Health Research, 20122012

• HIV a leader in the field of personalized HIV a leader in the field of personalized medicine with medications tailored to the medicine with medications tailored to the human and viral genomes human and viral genomes (Cheng, Carbonell & (Cheng, Carbonell & Macarthur, 2010)Macarthur, 2010)

• HLA pre-testing for Abacavir hypersensitivity HLA pre-testing for Abacavir hypersensitivity reactionreaction

• Tailoring antiretroviral therapy (ART) based Tailoring antiretroviral therapy (ART) based on patterns of drug resistanceon patterns of drug resistance

BackgroundBackground

• Antiretroviral drug resistance is known to Antiretroviral drug resistance is known to emerge with inadequate adherence to ART emerge with inadequate adherence to ART (Bangsberg et al, 2001)(Bangsberg et al, 2001)

• HIV-resistant strains can be transmitted HIV-resistant strains can be transmitted from one person to anotherfrom one person to another

• Antiretroviral resistance testing important Antiretroviral resistance testing important prior to initiating therapy and in the setting prior to initiating therapy and in the setting of virologic failure on ARTof virologic failure on ART

BackgroundBackground

Summary of situations in which Summary of situations in which resistance testing is resistance testing is

recommended recommended

Hirsch M S et al. Clin Infect Dis. 2003;37:113-128

• HIV-positive injection drug users demonstrate: HIV-positive injection drug users demonstrate:

• Lower levels of ART adherence Lower levels of ART adherence (Palepu et al., 2003)(Palepu et al., 2003)• Higher rates RNA viral load Higher rates RNA viral load (Rodriguez-Artenez et al., 2006)(Rodriguez-Artenez et al., 2006)• Higher rates ART discontinuation Higher rates ART discontinuation (Malta et al., 2008)(Malta et al., 2008)

• Antiretroviral therapy withheld from HIV-Antiretroviral therapy withheld from HIV-positive IDU over concerns of ART drug positive IDU over concerns of ART drug resistance resistance (Werb et al., 2010)(Werb et al., 2010)

• Not much known about the patterns of ART Not much known about the patterns of ART resistance testing among HIV-positive IDUresistance testing among HIV-positive IDU

BackgroundBackground

ObjectiveObjective

• Examine patterns of resistance testing Examine patterns of resistance testing among a cohort of injection drug users and among a cohort of injection drug users and factors associated with baseline ART factors associated with baseline ART resistance testing in a Canadian settingresistance testing in a Canadian setting

MethodsMethods

• The ACCESS cohort is an ongoing prospective The ACCESS cohort is an ongoing prospective cohort of HIV-positive individuals who inject drugscohort of HIV-positive individuals who inject drugs

• Participants recruited through self-referral and Participants recruited through self-referral and street outreach from Vancouver’s Downtown street outreach from Vancouver’s Downtown Eastside since 1996Eastside since 1996

• At baseline and semi-annually participants provide At baseline and semi-annually participants provide blood sample and complete questionnaireblood sample and complete questionnaire

MethodsMethods

• Primary outcome of interest: Primary outcome of interest: antiretroviral antiretroviral resistance testing prior to initiation of ARTresistance testing prior to initiation of ART

• Variables:Variables: Gender, age, ethnicityGender, age, ethnicity Physician experiencePhysician experience Baseline viral load (per logBaseline viral load (per log1010)) Baseline CD4 cell count (per 100 cells/mmBaseline CD4 cell count (per 100 cells/mm33))

• Multivariate logistic regression model fit using an Multivariate logistic regression model fit using an a a prioripriori defined model-building approach defined model-building approach

Did the participant undergo ART resistance testing prior to treatment?

Yes No

ResultsResults• Sample characteristics (n=854): Sample characteristics (n=854):

595 (70.0%) ART-naïve participants initiated therapy595 (70.0%) ART-naïve participants initiated therapy 231 (39.1%) female respondents231 (39.1%) female respondents 229 (38.5%) Aboriginal ancestry229 (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:

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

Baseline Baseline ART ART

resistance resistance testtest

Year of ART Year of ART initiationinitiation

1.251.25((0.19 – 1.31)0.19 – 1.31)

p p < 0.001< 0.001

Adjusted** Odds RatioAdjusted** Odds Ratio(95% CIs)(95% CIs)

Aboriginal ancestryAboriginal ancestry0.570.57((0.39 – 0.83)0.39 – 0.83)

p p < 0.001< 0.001

Plasma HIV-1 RNA*Plasma HIV-1 RNA*

* Time invariant, observed at baseline* Time invariant, observed at baseline

** Model was also adjusted for age, gender, CD4 count & physician experience** Model was also adjusted for age, gender, CD4 count & physician experience

• Multivariate Logistic Regression analysesMultivariate Logistic Regression analyses

1.481.48((1.20 – 1.83)1.20 – 1.83)

p p < 0.001< 0.001

Multivariate logistic regression analysis of factors Multivariate logistic regression analysis of factors independently associated with independently associated with >> 1 viral resistance test 1 viral resistance test pre-ART initiationpre-ART initiation

InterpretationsInterpretations

• Significant increase in antiretroviral Significant increase in antiretroviral resistance testing 1996 – 2010resistance testing 1996 – 2010

• Aboriginal ancestry negatively associated Aboriginal ancestry negatively associated with baseline ART resistance testingwith baseline ART resistance testing

• Aboriginal ancestry 50% less likely to Aboriginal ancestry 50% less likely to receive baseline testing after adjusting for receive baseline testing after adjusting for viral load and year of ART initiationviral load and year of ART initiation

InterpretationsInterpretations

• Multiple structural barriers to wellness faced Multiple structural barriers to wellness faced by people of Aboriginal ethnicity by people of Aboriginal ethnicity (Royal Commission on Aboriginal Peoples, 1996)

• Slower uptake of ART and disproportionate Slower uptake of ART and disproportionate number never access treatment number never access treatment (Wood et al., 2006)

• Urgent need for culturally sensitive Urgent need for culturally sensitive interventions to address inequities in interventions to address inequities in HIV care for this populationHIV care for this population

LimitationsLimitations

• Sample not randomly selected, findings may not Sample not randomly selected, findings may not generalize to other IDUgeneralize to other IDU

• Relationships between explanatory variable and Relationships between explanatory variable and outcome of interest may be subject to unobserved outcome of interest may be subject to unobserved confoundingconfounding

• Further research needed to examine barriers to Further research needed to examine barriers to testing in developing regions where ART is testing in developing regions where ART is expected to increase expected to increase

ConclusionConclusion

• Levels of resistance testing have Levels of resistance testing have significantly increased in accordance significantly increased in accordance with guidelines with guidelines

• Individuals of Aboriginal ethnicity Individuals of Aboriginal ethnicity continue to experience lower rates of continue to experience lower rates of resistance testingresistance testing

• Careful attention must be paid to Careful attention must be paid to delivering health care consistent with delivering health care consistent with guidelinesguidelines

AcknowledgementsAcknowledgements

• ACCESS participantsACCESS participants• ACCESS investigators and staffACCESS investigators and staff: : Deborah

Graham, Peter Vann, Caitlin Johnston, Steve Kain, and Calvin Lai

• US National Institutes of Health