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SUPPLEMENTAL DIGITAL CONTENT

Supplementary Table 1. Factors associated with moderate to extremely severe symptoms of depression among participants with chronic HCV infection and a history of injecting drug use in the ETHOS study (n=401)

Depression symptoms, n (%) Unadjusted Model 1^* Model 2^** Model 3^***

Characteristics Normal to mild Moderate to

extremely severe OR (95% CI) Adjusted OR (95% CI)

Adjusted OR (95% CI)

Adjusted OR (95% CI) Age

Mean (±SD) 40.61 (±8.75) 41.15 (±9.95) - - - ^-

Per 10 year increase - - 1.08 (0.86-1.34) 1.16 (0.91-1.48) 1.21 (0.94-1.57) -

Gender

Female 60 (29) 56 (29) 1.00 1.00 1.00 -

Male 145 (70) 139 (71) 1.03 (0.67-1.58) 1.02 (0.64-1.60) 0.95 (0.59-1.52) -

Part- or full-time employment

Yes 24 (12) 11 (6) 1.00 1.00 1.00 -

No 182 (88) 184 (94) 2.21 (1.05-4.63) 1.88 (0.85-4.14) 1.80 (0.81-4.00) -

Finished high school or higher education

Yes 36 (17) 37 (19) 1.00 1.00 1.00 -

No 170 (83) 158 (81) 0.90 (0.54-1.50) 0.95 (0.56-1.62) 0.93 (0.53-1.63) -

Housing status^¥

Stable 181 (88) 162 (83) 1.00 1.00 1.00 -

Unstable 25 (12) 32 (16) 1.43 (0.81-2.51) 1.37 (0.76-2.48) 1.02 (0.54-1.92) -

Living with a spouse or other relatives/friends

Yes 128 (62) 105 (54) 1.00 1.00 1.00 -

No 78 (38) 90 (46) 1.41 (0.94-2.09) 1.28 (0.84-1.94) 1.12 (0.72-1.74) -

Recent injecting drug use^¥

No 79 (38) 61 (31) 1.00 1.00 1.00 1.00

Yes 127 (62) 134 (69) 1.81 (1.22-2.69)^ǂ 1.63 (1.07-2.49) 1.53 (0.98-2.38) 1.81 (1.22-2.69)

High risk alcohol consumption (AUDIT-C)

No 144 (70) 123 (63) 1.00 1.00 1.00 -

Yes 62 (30) 72 (37) 1.36 (0.90-2.06) 1.35 (0.87-2.10) 1.27 (0.80-2.00) -

OST

Never 29 (14) 19 (10) 1.00 1.00

§

-

Previous, not current 14 (7) 11 (6) 1.20 (0.45-3.19) 1.20 (0.43-3.36) -

Current 163 (79) 165 (85) 1.55 (0.83-2.87) 1.45 (0.73-2.86) -

¥In the six months prior to study enrolment. ^ǂIndividual ORs (95% CI): heroin, 1.95 (1.28-2.97); morphine, 1.85 (1.03-3.32); methamphetamine, 1.41 (0.89-2.24); cocaine, 4.05 (1.47-

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Supplementary Table 2. Factors associated with moderate to extremely severe symptoms of anxiety among participants with chronic HCV infection and a history of injecting drug use in the ETHOS study (n=401)

Anxiety symptoms, n (%) Unadjusted Model 1^* Model 2^** Model 3^***

Characteristics Normal to mild Moderate to

Mean (±SD) 40.70 (±8.58) 41.02 (±9.08) - - - ^-

Gender

Female 56 (30) 60 (28) 1.00 1.00 1.00 -

Male 129 (69) 155 (72) 1.12 (0.73-1.73) 1.13 (0.72-1.77) 1.06 (0.65-1.72) -

Yes 23 (12) 12 (6) 1.00 1.00 1.00 -

No 163 (88) 203 (94) 2.39 (1.15-4.94) 2.04 (0.95-4.41) 2.09 (0.95-4.60) 2.39 (1.15-4.94)

Yes 35 (19) 38 (18) 1.00 1.00 1.00 -

No 151 (81) 177 (82) 1.08 (0.65-1.79) 1.09 (0.64-1.85) 1.17 (0.66-2.06) -

Housing status^¥

Stable 164 (88) 179 (83) 1.00 1.00 1.00 -

Unstable 22 (12) 35 (16) 1.46 (0.82-2.59) 1.38 (0.76-2.51) 0.93 (0.48-1.80) -

Yes 118 (63) 115 (53) 1.00 1.00 1.00 -

No 68 (37) 100 (47) 1.51 (1.01-2.25) 1.44 (0.95-2.19) 1.25 (0.80-1.96) -

No 70 (38) 70 (33) 1.00 1.00 1.00 -

Yes 116 (62) 145 (67) 1.49 (1.00-2.21)^ǂ 1.37 (0.90-2.09) 1.11 (0.70-1.75) -

No 128 (69) 139 (65) 1.00 1.00 1.00 -

Yes 58 (31) 76 (35) 1.21 (0.79-1.83) 1.19 (0.77-1.85) 1.10 (0.69-1.75) -

OST

Never 24 (13) 24 (11) 1.00 1.00

§

-

Current 148 (80) 180 (84) 1.22 (0.66-2.23) 1.09 (0.56-2.13) -

¥In the six months prior to study enrolment. ^ǂIndividual ORs (95% CI): heroin, 1.51 (0.99-2.29); morphine, 1.48 (0.83-2.66); methamphetamine, 1.21 (0.76-1.92); cocaine, 4.36 (1.46- 13.06); benzodiazepine, 4.90 (1.07-22.42). ^*Model 1: adjusted for all variables in the final model. ^**Model 2: adjusted for site. ^***Model 3: modelled using a stepwise backwards elimination. ^§OST and site could not be included in the same models, given that some sites were specifically OST sites.

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Supplementary Table 3. Factors associated with moderate to extremely severe symptoms of stress among participants with chronic HCV infection and a history of injecting drug use in the ETHOS study (n=401)

Stress symptoms, n (%) Unadjusted Model 1^* Model 2^** Model 3^***

Characteristics Normal to mild Moderate to

Mean (±SD) 41.00 (±8.94) 40.65 (±8.71) - - - -

Gender

Female 75 (30) 41 (28) 1.00 1.00 1.00

Male 177 (70) 107 (72) 1.11 (0.71-1.73) 1.12 (0.70-1.80) 1.07 (0.65-1.75) -

Yes 30 (12) 5 (3) 1.00 1.00 1.00

No 223 (88) 143 (97) 3.85 (1.46-10.15) 2.99 (1.09-8.15) 2.93 (1.06-8.10) 3.42 (1.29-9.11)

Yes 48 (19) 25 (17) 1.00 1.00 1.00

No 205 (81) 123 (83) 1.15 (0.68-1.96) 1.16 (0.66-2.03) 1.17 (0.65-2.12) -

Housing status^¥

Stable 222 (88) 121 (82) 1.00 1.00 1.00

Unstable 30 (12) 27 (18) 1.65 (0.94-2.91) 1.53 (0.84-2.76) 1.19 (0.63-2.26) -

Yes 158 (62) 75 (51) 1.00 1.00 1.00

No 95 (38) 73 (49) 1.62 (1.07-2.44) 1.55 (1.01-2.39) 1.41 (0.90-2.23) 1.54 (1.02-2.34)

No 99 (39) 41 (28) 1.00 1.00 1.00

Yes 154 (61) 107 (72) 1.75 (1.16-2.63)^ǂ 1.54 (0.99-2.39) 1.48 (0.93-2.35) 1.63 (1.07-2.47)

No 171 (68) 96 (65) 1.00 1.00 1.00

Yes 82 (32) 52 (35) 1.13 (0.74-1.73) 1.08 (0.68-1.71) 1.00 (0.62-1.61) -

OST

Never 35 (14) 13 (9) 1.00 1.00

§

-

Current 200 (79) 128 (86) 1.72 (0.88-3.38) 1.28 (0.61-2.68) -

¥In the six months prior to study enrolment. ^ǂIndividual ORs (95% CI): heroin, 1.59 (1.04-2.43); morphine, 1.16 (0.65-2.08); methamphetamine, 1.55 (0.97-2.48); cocaine, 2.82 (1.19-6.69);

benzodiazepine, 2.82 (0.91-8.79). ^*Model 1: adjusted for all variables in the final model. ^**Model 2: adjusted for site. ^***Model 3: modelled using a stepwise backwards elimination. ^§OST and site could not be included in the same models, given that some sites were specifically OST sites.

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Supplementary Table 4. Unadjusted analysis of factors associated with early HCV treatment intent, specialist assessment and HCV treatment uptake among participants with chronic HCV infection and a history of injecting drug use in the ETHOS study (n=415)

Early HCV treatment intent Assessed by specialist HCV treatment uptake

Characteristics OR (95% CI) OR (95% CI) OR (95% CI)

History of treated mental illness

No 1.00 1.00 1.00

Yes 0.72 (0.47-1.11)^* 0.90 (0.61-1.33)^** 0.59 (0.38-0.92)^***

Unknown 0.63 (0.20-1.97) 0.32 (0.10-1.05) 0.58 (0.16-2.15)

Psychological distress (DASS-21)^¶ Depression symptoms

Normal to mild 1.00 1.00 1.00

Moderate to extremely severe 0.71 (0.46-1.09) 0.69 (0.47-1.03) 0.63 (0.40-1.00) Anxiety symptoms

Moderate to extremely severe 0.86 (0.56-1.32) 0.94 (0.63-1.39) 0.78 (0.50-1.22) Stress symptoms

Moderate to extremely severe 0.81 (0.52-1.26) 0.87 (0.58-1.31) 0.56 (0.34-0.92)

¶401 participants answered the DASS-21 questionnaire.^*Individual ORs (95% CI): manic depression/bipolar disorder, 0.61 (0.27-1.36); schizophrenia, 3.34 (0.75-14.82); depression, 0.58 (0.36-0.95); anxiety, 0.91 (0.31-2.69); drug induced psychosis, 1.05 (0.27-4.04). ^**Individual ORs (95% CI): manic depression/bipolar disorder, 0.91 (0.42-1.96); schizophrenia, 1.29 (0.51-3.26); depression, 0.84 (0.53-1.32); anxiety, 1.00 (0.38-2.63); drug induced psychosis, 0.80 (0.25-2.55). ^***Individual ORs (95% CI): manic depression/bipolar disorder, 0.53 (0.21-1.36); schizophrenia, 0.35 (0.10-1.24); depression, 0.61 (0.36-1.03); anxiety, 0.82 (0.28-2.39); drug induced psychosis, 0.71 (0.19-2.70).

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Supplementary Table 5. Factors associated with early HCV treatment intent among participants with chronic HCV infection and a history of injecting drug use in the ETHOS study, adjusting for all variables in the final models (n=415)

Model 1^* Model 2^** Model 3^*** Model 4^****

Characteristics aOR (95% CI) aOR (95% CI) aOR (95% CI) aOR (95% CI)

Age

<35 1.00 1.00 1.00 1.00

35-45 2.02 (1.15-3.57) 1.97 (1.13-3.43) 2.00 (1.15-3.50) 1.99 (1.14-3.48)

≥45 0.96 (0.53-1.72) 0.98 (0.55-1.75) 0.97 (0.55-1.74) 0.97 (0.54-1.74)

Employment status

No part- or full-time employment 1.00 1.00 1.00 1.00

Part- or full-time employment 1.41 (0.56-3.59) 1.42 (0.56-3.6) 1.47 (0.58-3.73) 1.45 (0.57-3.67) Finished high school or higher education

No 1.00 1.00 1.00 1.00

Yes 1.06 (0.59-1.90) 1.08 (0.60-1.93) 1.07 (0.60-1.92) 1.07 (0.60-1.91)

No 1.00 1.00 1.00 1.00

Yes 1.58 (0.99-2.51) 1.55 (0.98-2.45) 1.56 (0.98-2.47) 1.55 (0.98-2.46)

Benzodiazepine use^¥

Yes 1.00 1.00 1.00 1.00

No 1.17 (0.72-1.88) 1.18 (0.74-1.89) 1.22 (0.76-1.96) 1.21 (0.75-1.93)

OST

Current 1.00 1.00 1.00 1.00

Previous, not current 1.49 (0.56-3.95) 1.47 (0.55-3.90) 1.46 (0.55-3.88) 1.46 (0.55-3.88) Never 3.79 (1.52-9.48) 3.41 (1.35-8.66) 3.45 (1.36-8.75) 3.44 (1.35-8.71) HCV genotype

1 1.00 1.00 1.00 1.00

2, 3, 4, 6, mixed 2.01 (1.25-3.25) 2.02 (1.25-3.26) 1.99 (1.23-3.21) 1.99 (1.24-3.21) Unknown 0.97 (0.46-2.04) 0.96 (0.46-2.01) 0.94 (0.45-1.96) 0.94 (0.45-1.96)

No 1.00 - - -

Yes 0.89 (0.55-1.44) - - -

Unknown 0.53 (0.16-1.76) - - -

DASS-21^¶

Depression symptoms

Normal to mild - 1.00 - -

Moderate to extremely severe - 0.81 (0.51-1.27) - -

Anxiety symptoms

Normal to mild - - 1.00 -

Moderate to extremely severe - - 1.01 (0.64-1.61) -

Stress symptoms

Normal to mild - - - 1.00

Moderate to extremely severe - - - 0.94 (0.59-1.51)

¥In the six months prior to study enrolment. ^¶401 participants answered the DASS-21 questionnaire. ^*Model 1: adjusted for history of treated mental illness. ^**Model 2: adjusted for depression symptoms. ^***Model 3: adjusted for anxiety symptoms. ^****Model 4: adjusted for stress symptoms.

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Supplementary Table 6. Factors associated with HCV specialist assessment among participants with chronic HCV infection and a history of injecting drug use in the ETHOS study, adjusting for all variables in the final models (n=415)

Age

<35 1.00 1.00 1.00 1.00

35-45 1.39 (0.82-2.35) 1.31 (0.78-2.19) 1.34 (0.80-2.25) 1.33 (0.79-2.23)

≥45 1.92 (1.08-3.39) 1.94 (1.10-3.43) 1.92 (1.08-3.39) 1.91 (1.08-3.38)

Employment status

No 1.00 1.00 1.00 1.00

Yes 2.08 (1.17-3.69) 2.16 (1.21-3.83) 2.13 (1.20-3.77) 2.13 (1.20-3.77)

No 1.00 1.00 1.00 1.00

Yes 1.26 (0.81-1.96) 1.20 (0.77-1.87) 1.24 (0.79-1.92) 1.23 (0.79-1.92)

Yes 1.00 1.00 1.00 1.00

No 1.51 (0.96-2.37) 1.47 (0.94-2.29) 1.53 (0.98-2.39) 1.51 (0.97-2.37)

OST

Current 1.00 1.00 1.00 1.00

1 1.00 1.00 1.00 1.00

2, 3, 4, 6, mixed 1.74 (1.13-2.7) 1.78 (1.15-2.76) 1.74 (1.13-2.69) 1.74 (1.13-2.69) Unknown 0.27 (0.11-0.66) 0.27 (0.11-0.66) 0.27 (0.11-0.64) 0.26 (0.11-0.64)

No 1.00 - - -

Yes 1.06 (0.68-1.66) - - -

Unknown 0.46 (0.13-1.65) - - -

DASS-21^¶

Depression symptoms

Anxiety symptoms

Stress symptoms

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Supplementary Table 7. Factors associated with HCV treatment uptake among participants with chronic HCV infection and a history of injecting drug use in the ETHOS study, adjusting for all variables in the final models (n=415)

Age

<35 1.00 1.00 1.00 1.00

35-45 1.73 (0.90-3.34) 1.81 (0.94-3.47) 1.82 (0.95-3.49) 1.84 (0.96-3.53)

≥45 1.41 (0.70-2.83) 1.45 (0.72-2.92) 1.42 (0.71-2.86) 1.43 (0.71-2.87)

Employment status

No 1.00 1.00 1.00 1.00

Yes 2.73 (1.46-5.10) 2.68 (1.43-5.00) 2.62 (1.41-4.88) 2.59 (1.39-4.84)

No 1.00 1.00 1.00 1.00

Yes 2.17 (1.27-3.72) 2.09 (1.22-3.59) 2.14 (1.25-3.67) 2.06 (1.20-3.54)

Yes 1.00 1.00 1.00 1.00

No 1.65 (0.94-2.88) 1.68 (0.97-2.92) 1.71 (0.98-2.99) 1.64 (0.94-2.86)

OST

Current 1.00 1.00 1.00 1.00

1 1.00 1.00 1.00 1.00

2, 3, 4, 6, mixed 2.64 (1.57-4.43) 2.69 (1.59-4.54) 2.63 (1.57-4.43) 2.65 (1.57-4.46) Unknown 0.09 (0.01-0.77) 0.10 (0.01-0.84) 0.10 (0.01-0.82) 0.10 (0.01-0.83)

No 1.00 - - -

Yes 0.74 (0.44-1.25) - - -

Unknown 0.93 (0.22-3.92) - - -

DASS-21^¶

Depression symptoms

Anxiety symptoms

Stress symptoms