1 The impact of ongoing illicit drug use on virologic suppression in HIV-infected injection drug users receiving HAART Authors: Harout Tossonian, Jesse Raffa, Jason Grebely, Behroz Rashidi, Stanley DeVlaming, Brian Conway XVII International AIDS Conference Mexico City Date: August 07, 2008

2 Introduction   Injection drug users (IDUs): Increasing globally 125,000 across Canada 6,000 on Downtown East Side of Vancouver Cocaine and heroin predominant drugs used   Antiretroviral therapy: May be less adherent to HAART May not respond to treatment as other patient groups May be less likely to achieve virologic suppression

Introduction   Studies : IDUs as likely to achieve virologic suppression as non-IDUs (Palepu et al., AIDS 2001) Active drug use associated with lower adherence to HAART and poorer clinical outcomes (Lucas et al, JAIDS 2001; Arnsten et al, J Gen Intern Med 2002; Palepu et al, JAIDS 2003) Within directly observed therapy (DOT) program, active drug use not associated with virologic failure (Conway et al, CID 2004) Within DOT setting, active drug use associated with non- adherence and non-retention but not with virologic failure (Lucas et al., AIDS Patient Care STDS 2007)

4 Objective To evaluate the impact of ongoing illicit drug use on virologic suppression in HIV- infected IDUs receiving HAART

5 Methods   Study and Population: Longitudinal prospective and retrospective cohort study HIV-infected IDUs who were prescribed HAART Pender Community Health Centre Downtown East Side of Vancouver, Canada Multidisciplinary approach   Regimens: DOT or self-administered therapy Methadone maintenance treatment Between August 1996 and August 2007 NNRTIs or PIs along with 2 NRTIs

6 Methods   Urine specimens for toxicology assays were analyzed: Amphetamines (A) Benzodiazepines (B) Cocaine (C) Heroin/opiates (O)   Ability to achieve virologic suppression was measured as a function of having a positive or negative (cumulative) urinalysis: At baseline During 6 months prior to treatment initiation During 12 months prior to treatment initiation

7 Methods   Virologic suppression: Measured at weeks 24 and 48 Based on intent-to-treat analysis HIV RNA < 400 copies/mL   Illicit drug use associated with virologic suppression: Multiple logistic regression models Adjusting for potential confounders Including age, sex, hepatitis C status, DOT, dosing frequency, regimen group, continuity of treatment, pre- HAART exposure and line of therapy

8 Results Number of patients Number of patients Males (%) Males (%) Mean age in years (SD) Mean age in years (SD) Hepatitis C antibody positive (%) Hepatitis C antibody positive (%) Mean CD4 (SD) cells/mm 3 Mean CD4 (SD) cells/mm 3 Median Viral load (Q1-Q3) copies/mL Median Viral load (Q1-Q3) copies/mL Treatment administration: DOT (%) Treatment administration: DOT (%) Pre-HAART exposure (%) Pre-HAART exposure (%) Median regimen duration in years (Q1-Q3) Median regimen duration in years (Q1-Q3) Regimen based on: NRTIs/NNRTIs/PIs Regimen based on: NRTIs/NNRTIs/PIs Dosing frequency: Once/Twice/Thrice Dosing frequency: Once/Twice/Thrice Line of therapy: 1 st /2 nd /3 rd />3 rd Line of therapy: 1 st /2 nd /3 rd />3 rd (59) 37.3 (7.7) 130 (98) 235 (203) 235 (203) 33,400 (1,180 - >100,000) 115 (86) 35 (26) 1.00 ( ) 5/21/10790/41/217/48/58/10 Baseline patient characteristics

9 Virologic suppression vs. positive or negative urinalysis (N=97) for illicit drugs at baseline A= Amphetamines; B= Benzodiazepines; C= Cocaine; O= Heroin/Opiates

10 Virologic suppression vs. positive or negative urinalysis (N=122) during the 6 months prior to treatment A= Amphetamines; B= Benzodiazepines; C= Cocaine; O= Heroin/Opiates

11 Virologic suppression vs. positive or negative urinalysis (N=133) during the 12 months prior to treatment A= Amphetamines; B= Benzodiazepines; C= Cocaine; O= Heroin/Opiates

12 Factors associated with virologic suppression at week 24Factor Adjusted Odds Ratio 95% C. I. p-value Baseline B 6 months B 12 months B Baseline C 6 months C 12 months C Baseline O 6 months O 12 months O Baseline A/B/C/O 6 months A/B/C/O 12 months A/B/C/O Baseline A/C/O 6 months A/C/O 12 months A/C/O

13 Factors associated with virologic suppression at week 24Factor Adjusted Odds Ratio 95% C. I. p-value Baseline B 6 months B 12 months B Baseline C 6 months C 12 months C Baseline O 6 months O 12 months O Baseline A/B/C/O 6 months A/B/C/O 12 months A/B/C/O Baseline A/C/O 6 months A/C/O 12 months A/C/O

14 Factor Adjusted Odds Ratio 95% C. I. p-value Baseline B 6 months B 12 months B Baseline C 6 months C 12 months C Baseline O 6 months O 12 months O Baseline A/B/C/O 6 months A/B/C/O 12 months A/B/C/O Baseline A/C/O 6 months A/C/O 12 months A/C/O Factors associated with virologic suppression at week 48

15 Factor Adjusted Odds Ratio 95% C. I. p-value Baseline B 6 months B 12 months B Baseline C 6 months C 12 months C Baseline O 6 months O 12 months O Baseline A/B/C/O 6 months A/B/C/O 12 months A/B/C/O Baseline A/C/O 6 months A/C/O 12 months A/C/O Factors associated with virologic suppression at week 48

16 Discussion   Similar rates of virologic suppression were achieved at weeks 24 and 48, in patients with positive and negative urinalyses for illicit drugs at baseline, as well as within the 6 and 12 months prior to treatment initiation   Having a positive urinalysis result for cocaine, at baseline and in the 6 months prior to treatment, was significantly associated with virologic failure at week 24

17 Discussion   Having a positive urinalysis result for benzodiazepines in the 12 months prior to treatment was significantly associated with virologic suppression at week 48, possibly linked to legitimate uses of benzodiazepines   Other illicit drug use was not associated with treatment failure at all other assessment points

18 Discussion   Structured programs for the delivery of HAART may be successful despite ongoing illicit drug use. Such use is not a contraindication to initiate HAART if treatment is medically indicated   Innovative or modified strategies (within the context of DOT) for the treatment of HIV infection among IDUs who abuse cocaine may be necessary to ensure optimal levels of virologic suppression are achieved in this population

19 Acknowledgements  Dr. Brian Conway  Mr. Jesse Raffa  Pender Community Health Centre  University of British Columbia  Boehringer Ingelheim Canada  Canadian Institutes of Health Research (CIHR)  AIDS 2008