1 the impact of ongoing illicit drug use on virologic suppression in hiv-infected injection drug...
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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
Suppression at Week 48
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%
A B C O A/B/C/O A/C/O
Suppression at Week 24
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%
A B C O A/B/C/O A/C/O
Suppression at Week 48
POS
NEG
A= Amphetamines; B= Benzodiazepines; C= Cocaine; O= Heroin/Opiates
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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%
A B C O A/B/C/O A/C/O
Suppression at Week 24
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
Suppression at Week 48
POS
NEG
A= Amphetamines; B= Benzodiazepines; C= Cocaine; O= Heroin/Opiates
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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
12 months B12 months B
Baseline CBaseline C
6 months C6 months C
12 months C12 months C
Baseline OBaseline O
6 months O6 months O
12 months O12 months O
Baseline Baseline A/B/C/OA/B/C/O
6 months 6 months A/B/C/OA/B/C/O
12 months 12 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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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
12 months B12 months B
Baseline CBaseline C
6 months C6 months C
12 months C12 months C
Baseline OBaseline O
6 months O6 months O
12 months O12 months O
Baseline Baseline A/B/C/OA/B/C/O
6 months 6 months A/B/C/OA/B/C/O
12 months 12 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
0.85-0.85-7.057.05
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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FactorFactor Adjusted Odds Adjusted Odds RatioRatio
95% C. I.95% C. I. p-valuep-value
Baseline BBaseline B
6 months B6 months B
12 months B12 months B
Baseline CBaseline C
6 months C6 months C
12 months C12 months C
Baseline OBaseline O
6 months O6 months O
12 months O12 months O
Baseline A/B/C/OBaseline A/B/C/O
6 months 6 months A/B/C/OA/B/C/O
12 months 12 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 A/C/O12 months A/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
Factors associated with virologic suppression at week 48
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FactorFactor Adjusted Odds Adjusted Odds RatioRatio
95% C. I.95% C. I. p-valuep-value
Baseline BBaseline B
6 months B6 months B
12 months B12 months B
Baseline CBaseline C
6 months C6 months C
12 months C12 months C
Baseline OBaseline O
6 months O6 months O
12 months O12 months O
Baseline A/B/C/OBaseline A/B/C/O
6 months 6 months A/B/C/OA/B/C/O
12 months 12 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 A/C/O12 months A/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
Factors associated with virologic suppression at week 48
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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