1 The impact of ongoing illicit drug use on virologic suppression in HIV-infected injection drug users receiving HAART Authors: Harout Tossonian, Jesse

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The impact of ongoing illicit drug The impact of ongoing illicit drug use on virologic suppression in HIV-use on virologic suppression in HIV-infected injection drug users infected injection drug users receiving HAARTreceiving HAART

Authors: Authors: Harout TossonianHarout Tossonian, Jesse , Jesse Raffa, Jason Grebely, Behroz Raffa, Jason Grebely, Behroz Rashidi, Stanley DeVlaming, Brian Rashidi, Stanley DeVlaming, Brian ConwayConway

XVII International AIDS XVII International AIDS ConferenceConferenceMexico CityMexico CityDate: August 07, 2008Date: August 07, 2008

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IntroductionIntroduction

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)

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ObjectiveObjective

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

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MethodsMethods 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

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MethodsMethods 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

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MethodsMethods 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

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ResultsResults

Number of patientsNumber 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/mmMean CD4 (SD) cells/mm33

Median Viral load (Q1-Q3) Median Viral load (Q1-Q3) copies/mLcopies/mL

Treatment administration: DOT Treatment administration: DOT (%)(%)

Pre-HAART exposure (%)Pre-HAART exposure (%)

Median regimen duration in Median regimen duration in years (Q1-Q3)years (Q1-Q3)

Regimen based on: Regimen based on: NRTIs/NNRTIs/PIsNRTIs/NNRTIs/PIs

Dosing frequency: Dosing frequency: Once/Twice/ThriceOnce/Twice/Thrice

Line of therapy: 1Line of therapy: 1stst/2/2ndnd/3/3rdrd/>3/>3rdrd

133133

79 (59)79 (59)

37.3 (7.7)37.3 (7.7)

130 (98)130 (98)

235 (203)235 (203)

33,400 (1,180 - 33,400 (1,180 - >100,000)>100,000)

115 (86)115 (86)

35 (26)35 (26)

1.00 (0.50-2.00)1.00 (0.50-2.00)

5/21/1075/21/107

90/41/2 90/41/2

17/48/58/1017/48/58/10

Baseline patient characteristics

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Virologic suppression vs. positive or negative urinalysis (N=97) for illicit drugs at baseline

33%

1/ 3

60%

18/ 30

42%

23/ 55

48%

16/ 33

48%

32/ 67

48%

32/ 67

53%

50/ 94

49%

33/ 67

67%

28/ 42

55%

35/ 64

63%

19/ 30

63%

19/ 30

0%10%20%30%40%50%60%70%80%

A B C O A/B/C/O A/C/O

Suppression at Week 24

33%

1/ 3

50%

15/ 30

40%

22/ 55

39%

13/ 33

42%

28/ 67

42%

28/ 67

41%

39/ 94

37%

25/ 67

43%

18/ 42

42%

27/ 64

40%

12/ 30

40%

12/ 30

0%

10%

20%30%

40%

50%

60%

A B C O A/ B/ C/ O A/ C/ O


POS

NEG

A= Amphetamines; B= Benzodiazepines; C= Cocaine; O= Heroin/Opiates

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Virologic suppression vs. positive or negative urinalysis (N=122) during the 6

months prior to treatment

48%

48/ 100

47%

7/ 15

55%

32/ 58

47%

44/ 93

53%

39/ 74

49%

50/ 103

64%

14/ 22

63%

12/ 19

51%

55/ 107

47%

30/ 64

38%

11/ 29

48%

23/ 48

0%10%20%30%40%50%60%70%



40%

40/ 100

41%

42/ 103

42%

31/ 74

41%

38/ 93

45%

26/ 58

47%

7/ 15

32%

7/ 22

26%

5/ 19

33%

16/ 48

31%

9/ 29

33%

21/ 64

37%

40/ 107

0%

10%

20%

30%

40%

50%



POS

NEG


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Virologic suppression vs. positive or negative urinalysis (N=133) during the 12 months prior

to treatment

50%

56/ 113

50%

57/ 115

52%

46/ 89

50%

53/ 107

55%

36/ 66

43%

10/ 23

55%

11/ 20

56%

10/ 18

48%

21/ 44

54%

14/ 26

46%

31/ 67

52%

57/ 110

0%

10%

20%

30%

40%

50%

60%



38%

43/ 113

38%

44/ 115

38%

34/ 89

38%

41/ 107

47%

31/ 66

43%

10/ 23

25%

5/ 20

22%

4/ 18

32%

14/ 44

27%

7/ 26

25%

17/ 67

35%

38/ 110

0%

10%

20%

30%

40%

50%

A B C O A/ B/ C/ O A/ C/ O


POS

NEG


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Factors associated with virologic suppression at week 24

FactorFactor Adjusted Odds Adjusted Odds RatioRatio

95% C. I.95% C. I. p-valuep-value

Baseline BBaseline B

6 months B6 months B


Baseline CBaseline C

6 months C6 months C


Baseline OBaseline O

6 months O6 months O


Baseline Baseline A/B/C/OA/B/C/O

6 months 6 months A/B/C/OA/B/C/O


Baseline A/C/OBaseline A/C/O

6 months A/C/O6 months A/C/O

12 months 12 months A/C/OA/C/O

2.452.45

1.741.74

1.431.43

0.330.33

0.290.29

0.570.57

0.740.74

1.661.66

1.331.33

0.550.55

0.500.50

0.670.67

0.450.45

0.490.49

0.750.75

0.85-7.050.85-7.05

0.75-4.010.75-4.01

0.66-3.080.66-3.08

0.12-0.870.12-0.87

0.10-0.890.10-0.89

0.19-1.700.19-1.70

0.26-2.080.26-2.08

0.69-4.030.69-4.03

0.56-3.150.56-3.15

0.22-1.390.22-1.39

0.17-1.450.17-1.45

0.23-1.980.23-1.98

0.18-1.110.18-1.11

0.18-1.340.18-1.34

0.27-2.070.27-2.07

0.0960.096

0.190.19

0.360.36

0.0260.026

0.0300.030

0.320.32

0.570.57

0.260.26

0.520.52

0.210.21

0.200.20

0.470.47

0.0850.085

0.170.17

0.580.58

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Baseline Baseline A/B/C/OA/B/C/O





12 months 12 months A/C/OA/C/O

2.452.45

1.741.74

1.431.43

0.330.33

0.290.29

0.570.57

0.740.74

1.661.66

1.331.33

0.550.55

0.500.50

0.670.67

0.450.45

0.490.49

0.750.75

0.85-0.85-7.057.05

0.75-0.75-4.014.01

0.66-0.66-3.083.08

0.12-0.12-0.870.87

0.10-0.10-0.890.89

0.19-0.19-1.701.70

0.26-0.26-2.082.08

0.69-0.69-4.034.03

0.56-0.56-3.153.15

0.22-0.22-1.391.39

0.17-0.17-1.451.45

0.23-0.23-1.981.98

0.18-0.18-1.111.11

0.18-0.18-1.341.34

0.27-0.27-2.072.07

0.0960.096

0.190.19

0.360.36

0.0260.026

0.0300.030

0.320.32

0.570.57

0.260.26

0.520.52

0.210.21

0.200.20

0.470.47

0.0850.085

0.170.17

0.580.58

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Baseline A/B/C/OBaseline A/B/C/O






1.761.76

1.371.37

2.352.35

0.950.95

1.021.02

1.041.04

0.780.78

1.341.34

1.171.17

1.301.30

1.661.66

2.002.00

1.001.00

1.251.25

1.731.73

0.63-0.63-4.914.91

0.58-0.58-3.213.21

1.03-1.03-5.345.34

0.36-0.36-2.542.54

0.32-0.32-3.183.18

0.31-0.31-3.433.43

0.27-0.27-2.252.25

0.53-0.53-3.403.40

0.46-0.46-2.982.98

0.49-0.49-3.453.45

0.51-0.51-5.365.36

0.56-0.56-7.167.16

0.40-0.40-2.522.52

0.44-0.44-3.563.56

0.54-0.54-5.485.48

0.280.28

0.470.47

0.0420.042

0.920.92

0.980.98

0.950.95

0.640.64

0.540.54

0.740.74

0.600.60

0.400.40

0.290.29

0.990.99

0.670.67

0.360.36


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Baseline A/B/C/OBaseline A/B/C/O






1.761.76

1.371.37

2.352.35

0.950.95

1.021.02

1.041.04

0.780.78

1.341.34

1.171.17

1.301.30

1.661.66

2.002.00

1.001.00

1.251.25

1.731.73

0.63-4.910.63-4.91

0.58-3.210.58-3.21

1.03-5.341.03-5.34

0.36-2.540.36-2.54

0.32-3.180.32-3.18

0.31-3.430.31-3.43

0.27-2.250.27-2.25

0.53-3.400.53-3.40

0.46-2.980.46-2.98

0.49-3.450.49-3.45

0.51-5.360.51-5.36

0.56-7.160.56-7.16

0.40-2.520.40-2.52

0.44-3.560.44-3.56

0.54-5.480.54-5.48

0.280.28

0.470.47

0.0420.042

0.920.92

0.980.98

0.950.95

0.640.64

0.540.54

0.740.74

0.600.60

0.400.40

0.290.29

0.990.99

0.670.67

0.360.36


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DiscussionDiscussion 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

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DiscussionDiscussion

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

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DiscussionDiscussion

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

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AcknowledgementsAcknowledgements Dr. Brian ConwayDr. Brian Conway

Mr. Jesse RaffaMr. Jesse Raffa

Pender Community Health CentrePender Community Health Centre

University of British ColumbiaUniversity of British Columbia

Boehringer Ingelheim CanadaBoehringer Ingelheim Canada

Canadian Institutes of Health Canadian Institutes of Health Research (CIHR)Research (CIHR)

AIDS 2008AIDS 2008

Documents

1 The impact of ongoing illicit drug use on virologic suppression in HIV-infected injection drug users receiving HAART Authors: Harout Tossonian, Jesse