Follow-up investigation of a cluster of treatment-naïve HIV-infected patients with multi-drug resistance in Sudbury, Ontario

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1 Follow-up investigation of a cluster of treatment-naïve HIV-infected patients with multi-drug resistance in Sudbury, Ontario Ashleigh Sullivan, Penny Sutcliffe, Roger Sandre, P. Richard Harrigan, Chris Archibald, Jessica Halverson, Claudia Rank, James Brooks, Ann Burchell, Keyi Wu, Shannon Dowdall-Smith, Judy Latendre-Paquette, Robert S. Remis From: Public Health Ontario Public Health Agency of Canada Sudbury & District Health Unit HAVEN Program, Health Sciences North Dalla Lana School of Public Health, University of Toronto 22nd Annual Canadian HIV/AIDS Research Conference Vancouver, BC, April 11-14, 2013

2 Conflict of interest disclosure I have no conflicts of interest

3 Background: HIV drug resistance HIV drug resistance may reduce effectiveness of ART Need to monitor drug resistance to inform: Treatment options for individual patients Treatment guidelines Policy (e.g. treatment as prevention) Especially important to monitor drug resistance in treatment-naïve patients as an indicator of transmission of drug-resistant HIV strains

4 Background: Results of previous study Analyzed drug resistance in 2,118 HIV-positive patients in Ontario with genotyping prior to ART, 2005 to 2011 Overall, resistance by drug class was: NRTI 8.6%, NNRTI 5.6%, and PI 2.6%; 2.8% were multi-drug resistant (MDR) In Sudbury, Ontario, 53% were MDR, an unprecedented level of resistance

5 Sudbury HIV multi-drug resistance (MDR) Patients with MDR in Sudbury consistently had the following drug resistance mutations: NNRTI mutation K103N causes high level resistance to nevirapine and efavirenz NRTI mutations M41L and T215 revertant do not confer high level phenotype changes, but are significant and are one mutation away from M41L + T215Y, a combination which confers resistance to most NRTIs including: zidovudine, stavudine, didanosine, abacavir, and tenofovir

6 Study objectives Characterize the distribution of transmitted drug resistance among treatment-naïve patients in Sudbury Determine factors associated with MDR Examine access to care of persons diagnosed with HIV in Sudbury

7 Methods Case definition: Sudbury resident diagnosed with HIV from January 2005 to June 2012 Collected and reconciled data on: demographic characteristics, exposure category, race/ethnicity, and uptake of HIV care from: Public Health Ontario - HIV Laboratory HIV Laboratory Enhancement Program Sudbury & District Health Unit The HAVEN Program, Health Sciences North

8 Methods (continued) Sources of genotyping data: HIV genotyping prescribed on viral load specimens in the context of clinical care, BC Centre for Excellence Strain and Drug Resistance Program (SDR), Public Health Agency of Canada, on HIV diagnostic specimens Drug resistance results based on clinical genotyping results if available, and SDR otherwise Cases considered treatment-naïve if no ART and no prior undetectable viral load

9 Results: HIV cases 85 cases diagnosed in Sudbury Jan 2005 to Jun 2012 Majority (65%) male Average of 10.6 cases/year (range 3-19); no obvious trend over time Median age at diagnosis: 36 years (IQR 29, 44) Exposure category: IDU 63%, MSM 17%, MSM-IDU 7%, and other 14% Race/ethnicity: White 65%, Aboriginal 27%, and other 8%

10 Proportion treated at the HAVEN Program 89% attended the HAVEN Program at least once By sex: male 86%, female 97% By exposure category: IDU 94%, MSM-IDU 100%, MSM 79%, and other 75% By race/ethnicity: White 89%, Aboriginal 96%, and other 71% None of the above differences statistically significant

11 Attendance at the HAVEN Program (i.e. at least one visit) Proportion attended Overall 89% Sex Male 86% Female 97% Exposure category IDU 94% MSM-IDU 100% MSM 79% Other 75% Race/ ethnicity Aboriginal 96% White 89% Other 71% Differences were not statistically significant

12 HIV drug resistance by drug class 33% Drug resistance NRTI and NNRTI (MDR) 52% NRTI only NNRTI only No resistance 3% 12% Genotyping available for 78% (66/85) of cases; further analyses are restricted to cases which were genotyped

13 Multi-drug resistance by characteristics Tested MDR % MDR p value Sex Male % Female % Exposure category IDU % MSM-IDU % MSM % Other % <0.001 Race/ ethnicity Aboriginal % White % Other % Overall %

14 MDR rates by exposure category, sex, and race/ethnicity 100% IDU 100% Non-IDU Proportion resistant 80% 60% 40% 20% 0% Male Female Proportion resistant 80% 60% 40% 20% 0% Male Female 100% IDU 100% Non-IDU Proportion resistant 80% 60% 40% 20% 0% Aboriginal Non-Aboriginal Proportion resistant 80% 60% 40% 20% 0% Aboriginal Non-Aboriginal

15 Interpretation of MDR rates MDR rates much higher among IDUs, but also higher among women and Aboriginal persons However, there were more IDUs among women and Aboriginal persons Thus, the higher MDR rate among women and Aboriginal persons is likely entirely explained by the higher proportion of IDUs in these categories

16 MDR multivariate model Covariates Crude OR Adjusted OR P-value (adjusted) Age 0.97 ( ) 0.98 ( ) 0.56 Sex Male Female 3.5 ( ) 1.56 ( ) 0.52 Exposure category MSM & other IDU 44 ( ) 40 ( ) MSM-IDU 17 ( ) 22 ( ) Race/ethnicity Non-Aboriginal Aboriginal 2.1 ( ) 0.74 ( ) 0.66

17 Limitations 19 of 85 HIV-positive patients did not have a treatmentnaïve genotype People may have moved or sought care elsewhere Can assess drug resistance only in patients diagnosed Using genotyping data on specimens for clinical purposes may have introduced bias However, in Sudbury, patterns of drug resistance using HIV diagnostic specimens were the same as those from clinical genotyping

18 Conclusions HIV infection among IDU in Sudbury is an important public health problem Study confirms the need for routine HIV genotyping prior to treatment Aboriginal persons and women are over-represented in HIV cases and MDR, but related to injection drug use Access to care was, in general, excellent and did not vary significantly by patient characteristics High level of MDR HIV infection, especially among IDU, is of great potential concern

19 Future studies Examine clinical outcomes for patients in Sudbury with multi-drug resistance

20 Acknowledgements Stephanie Hastie, Gisele Sbrega, and support staff at Sudbury & District Health Unit Brenda Kirkbride at the HAVEN Program Health care workers who completed the Laboratory Enhancement Program (LEP) questionnaire Lisa Santangelo, Kevin McCurley for LEP data collection Public Health Agency of Canada for supporting this investigation and the Laboratory Enhancement Program AIDS Bureau, Ministry of Health and Long-Term Care for core support

21 Single-drug resistance (SDR) by characteristics Tested SDR % SDR p value Sex Male % Female % 0.74 Exposure category IDU % MSM-IDU % MSM % Other % 0.45 Race/ ethnicity Aboriginal % White % Other % 0.51 Overall %