BASELINE CHARACTERISTICS OF STUDY PATIENTS �������������������������������������������������������������������������������������������������������

Figure 1a below shows the patient outcomes in the overall MDR/RR-TB cohort in Minsk for the last years� From 2013 to 2018 there is a decrease in the number of patients enrolled into care and an increase in success rates - which is accompanied by a decrease in the treatment failure rate� LTFU and death rates remain fairly steady at around 10%�

There were 59 patients included from the Minsk PS MDR/RR-TB intervention in this analysis, of which 8 (13�6%) were female and 51 (86�4%) were male� The majority of patients had a history of either past incarceration 41 (69�5%), homelessness 8 (13�6%) or unemployment 37 (62�7%)� Amongst males, 21 (41�2%) were either married or living with a partner and the same figure for females was 5 (62�5%)� Amongst patients for whom data was available, 24 i�e� 100% were recorded as being smokers� The full baseline social characteristics, stratified by whether the patient was adherent to tuberculosis treatment or not can be seen in Table 2�

TABLE 2: BASELINE SOCIAL CHARACTERISTICS BY ADHERENCE STATUS

Gender

Age group

Marital Status >=90% adherence (N=38) N (%) <90% adherent (N=21) N (%) Overall (N=59) N (%)

- Female 7 (87�5) 1 (12�5) 8 (13�6) - Male 31 (60�8) 20 (39�2) 51 (86�4)

- <35 5 (62�5) 3 (37�5) 8 (13�6) - 35-55 26 (74�3) 9 (25�7) 35 (59�3) - >55 7 (43�8) 9 (56�2) 16 (27�1)

- In union 16 (61�5) 10 (38�5) 26 (44�1) - Single 13 (86�7) 2 (13�3) 15 (25�4) Widowed/divorced/Separated 9 (50�0) 9 (50�0) 18 (30�5)

Education level

- Did not finish school 1 (50�0) 1 (50�0) 2 (3�4) - Secondary 35 (66�0) 18 (34�0) 53 (89�8) - University 2 (50�0) 2 (50�0) 4 (6�8)

Employment status

History of Incarceration

- Employed 14 (63�6) 8 (36�4) 22 (37�3) - Unemployed 24 (64�9) 13 (35�1) 37 (62�7)

- Yes 26 (63�4) 15 (36�6) 41 (69�5) - No 12 (66�7) 6 (33�3) 18 (30�5)

Homeless status

Smoker

IV illicit drug use

- Homeless 6 (75�0) 2 (25�0) 8 (13�6) - Not homeless 32 (62�7) 19 (37�3) 51 (86�4)

- Yes 14 (58�3) 10 (41�7) 24 (100�0) - No 0 (0) 0 (0) 0 (0)

- Yes 1 (33�3) - No 6 (60�0) 2 (66�7) 3 (23�1) 4 (40�0) 10 (76�9)

p value

0�142 (1)

0�106 (1)

0�084 (1)

0�739 (1)

0�924 (1)

0�810 (1)

0�501 (1)

0�416 (1)

Non-IV illicit drug use

Discharge from Orsha Prison

Discharge from Volkovichi Forced Hospitalisation Centre (FHC)

(1) Pearson’s Chi-squared test

>=90% adherence (N=38) N (%) <90% adherent (N=21) N (%) Overall (N=59) N (%)

- Yes 1 (33�3) - No 5 (55�6) 2 (66�7) 3 (25�0) 4 (44�4) 9 (75�0)

- Yes 9 (81�8) 2 (18�2) 11 (19�3) - No 28 (60�9) 18 (39�1) 46 (80�7)

- Yes 4 (57�1) 3 (42�9) 7 (12�3) - No 33 (66�0) 17 (34�0) 50 (87�7)

p value

0�505 (1)

0�191 (1)

0�646 (1)

Table 3 shows the baseline medical characteristics stratified by whether or not they were adherent to TB treatment.

Amongst the MSF patients, adverse events (AE) were relatively common with 6 (23�1%) having one or two adverse events and 16 (61�5%) having 3 or more adverse events� One patient had a total of 9 adverse events and 5 others had serious adverse events recorded� Annex 5 describes the type of adverse events experienced�

In the cohort as a whole the most commonly recorded co-morbidity was Hepatitis C (n = 25, 42�4%), followed by HIV (n = 18, 30�5%) then heart disease (n = 12, 20�3%)�

TABLE 3: BASELINE MEDICAL CHARACTERISTICS BY ADHERENCE STATUS

Drug regimen

Regimen length >=90% Adherence (N=38) N (%) <90% adherent (N=21) N (%) Overall (N=59) N (%)

- BDQ 21 (65�6) 11 (34�4) 32 (54�2) - DLM and BDQ 15 (62�5) 9 (37�5) 24 (40�7) - NA 2 (66�7) 1 (33�3) 3 (5�1)

- Long (18-20m) regimen 28 (65�1) 15 (34�9) 43 (100�0) - Short regimen 10 (62�5) 6 (37�5) 16 (100�0)

WHO Treatment group

- New 19 (55�9) 15 (44�1) 34 (58�6) - Other previously treated patients 3 (100�0) 0 (0�0) 3 (5�2) - Relapse 10 (76�9) 3 (23�1) 13 (22�4) - Treatment After Failure 1 (50�0) 1 (50�0) 2 (3�4) - Treatment after loss to follow up 4 (66�7) 2 (33�3) 6 (10�3)

TB sub-classification

- Confirmed MDR 11 (78�6) 3 (21�4) 14 (23�7) - Confirmed pre-XDR (FQ) 7 (53�8) 6 (46�2) 13 (22�0) - Confirmed pre-XDR (Inj) 10 (66�7) 5 (33�3) 15 (25�4) - Confirmed XDR 9 (60�0) 6 (40�0) 15 (25�4) - R resistance with H susceptibility 1 (50�0) 1 (50�0) 2 (3�4)

p value

0�968 (1)

0�852 (1)

0�437 (1)

0�699 (1)

Previous history of TB

HIV status

Hepatitis C status

Hepatitis B status

Diabetes status

COPD

Cirrhosis

Renal illness

Heart disease

BMI >=90% Adherence (N=38) N (%) <90% adherent (N=21) N (%) Overall (N=59) N (%)

- Yes 19 (76�0) 6 (24�0) 25 (42�4) - No 19 (55�9) 15 (44�1) 34 (57�6)

- Positive 12 (66�7) 6 (33�3) 18 (31�0) - Negative 26 (65�0) 14 (35�0) 40 (69�0)

- Yes 14 (56�0) 11 (44�0) 25 (42�4) - No 24 (70�6) 10 (29�4) 34 (57�6)

- Yes 1 (50�0) 1 (50�0) 2 (3�4) - No 37 (64�9) 20 (35�1) 57 (96�6)

- Yes 1 (50�0) 1 (50�0) 2 (3�4) - No 37 (64�9) 20 (35�1) 57 (96�6)

- Yes 0 (0�0) 1 (100�0) 1 (1�7) - No 38 (65�5) 20 (34�5) 58 (98�3)

- Yes 3 (75�0) 1 (25�0) 4 (7�3) - No 32 (62�7) 19 (37�3) 51 (92�7)

- Yes 2 (50�0) 2 (50�0) 4 (6�8) - No 36 (65�5) 19 (34�5) 55 (93�2)

- Yes 8 (66�7) 4 (33�3) 12 (20�7) - No 30 (65�2) 16 (34�8) 46 (79�3)

- Underweight (<18�5) 1 (33�3) 2 (66�7) 3 (12�0) - Normal weight (18�5 to 25) 13 (68�4) 6 (31�6) 19 (76�0) - Overweight (25 to 30) 2 (66�7) 1 (33�3) 3 (12�0)

No. Adverse events (AE)

- 1-2 AE 4 (66�7) 2 (33�3) 6 (10�2) - 3+ AE 12 (75�0) 4 (25�0) 16 (27�1) - No AE 0 (0�0) 4 (100�0) 4 (6�8) - Unknown 22 (66�7) 11 (33�3) 33 (55�9)

Serious adverse events

- 1-2 SAE 1 (20�0) 4 (80�0) 5 (8�5) - No SAE 15 (71�4) 6 (28�6) 21 (35�6) - Unknown 22 (66�7) 11 (33�3) 33 (55�9)

(1) Pearson’s Chi-squared test

p value

0�111 (1)

0�902 (1)

0�247 (1)

0�665 (1)

0�665 (1)

0�175 (1)

0�624 (1)

0�533 (1)

0�925 (1)

0�498 (1)

0�044 (1)

0�090 (1)

Table 4 shows the baseline mental health characteristics� There were 24 (40�7%) patients who had been registered as having a disorder due to the use of drugs or alcohol and 5 (8�5%) who had been previously diagnosed with mental illness before cohort entry� This meant just over half had no formal psychiatric diagnosis before entry into the psychosocial support programme� At cohort entry all patients had a psychiatric diagnosis of some sort recorded� The most common type of diagnosis was a disorder due to the use of alcohol with 45 (76%) patients having a confirmed or suspected diagnosis of this at admission� Among the remaining 14 with no formal diagnosis there was only 1 who had a low score according to the AUDIT or ASSIST tools, but the patient was suspected by their counsellor to have problematic alcohol consumption� There were also a further 5 patients with opioid dependence, and amongst those with alcohol dependence 6 patients had a combination of alcohol and other drug dependence� The full breakdown of types of psychiatric disorder can be seen in Table 4� Only 3 patients are recorded as having a personality disorder diagnosis, though there are thought to be other patients who would meet the criteria for this diagnosis if the psychiatrist had gone through the full process of diagnosing it� It should also be noted that any patient with a more severe psychiatric disorder such as psychosis would be referred to another facility rather than treated in the cohort� When combining the results for the ASSIST and AUDIT scores 30 (50�8%) had moderate alcohol or other substance use, 12 (20�3%) had high levels of use and 15 (25�4%) self-report low use of substances� Self-reported alcohol use amongst women was considerably lower with 2 out of 8 women (25%) having moderate or high levels of alcohol use, compared to 40 out of 51 (78�4%) among males� Baseline reported IV drug use, for patients where data was available, was 1 out of 3 (33�3%) females and 2 out of 23 (8�7%) males� Males however were more likely to have hepatitis C with 24 out of 51 (47�1%) compared to 1 out of 8 females (12�5%) which may indicate higher levels of past drug use�

Levels of anxiety at baseline were generally low, with 48 patients (81�4%) reporting minimal levels of anxiety� Levels of anxiety among women were higher with 2 of 8 (25%) having moderate or severe anxiety, compared to 3 of 51 (5�9%) males�

The PHQ9 showed that 8 patients (13�6%) had moderate depression and 4 (6�8%) had moderately severe or severe depression� Levels of depression among women were similar to men with 2 of 8 (25%) women having moderate or severe depression, compared to 10 of 51 (19�6%) males�

Patient’s baseline motivation to complete treatment was variable with 25 (42�4%) reporting a high level of motivation and 5 (8�5%) a low level of motivation�

TABLE 4: BASELINE MENTAL HEALTH CHARACTERISTICS

>=90% Adherence (N=38) N (%) <90% adherent (N=21) N (%) Overall (N=59) N (%)

History of MH Issues

- Yes 2 (40�0) 3 (60�0) 5 (8�5) - No 36 (66�7) 18 (33�3) 54 (91�5)

MH Registered at narcological dispensary

- Yes 20 (58�8) 14 (41�2) 34 (58�6) - No 17 (70�8) 7 (29�2) 24 (41�4)

Other psychological illness

- Yes 34 (66�7) 17 (33�3) 51 (86�4) - No 4 (50�0) 4 (50�0) 8 (13�6)

Substance abuse diagnosis

- Alcohol dependence 23 (67�6) 11 (32�4) 34 (57�6) - Alcohol and other substance dependence 2 (33�3) 4 (66�7) 6 (10�2) - Opioid dependence 5 (100�0) 0 (0�0) 5 (8�5) - Acute alcohol intoxication 2 (66�7) 1 (33�3) 3 (5�1) - Alcohol amnesic syndrome and alcohol dependence 1 (50�0) 1 (50�0) 2 (3�4) - None recorded 5 (55�6) 4 (44�4) 9 (15�3)

p value

0�233 (1)

0�349 (1)

0�360 (1)

0�271 (2)

>=90% Adherence (N=38) N (%) <90% adherent (N=21) N (%) Overall (N=59) N (%)

Other psychiatric diagnosis

- Borderline personality disorder 2 (100�0) 0 (0�0) 2 (3�4)

- Other personality/behavioural disorder due to physical cond� 1 (100�0) 0 (0�0) 1 (1�7)

- Other MH disorder due to phys cond� 0 (0�0) - Toximetabolic encephalopathy 1 (100�0) 1 (100�0) 1 (1�7) 0 (0�0) 1 (1�7)

- Reaction to stress 1 (100�0) 0 (0�0)

1 (1�7) - Mild intellectual disabilities 0 (0�0) 1 (100�0) 1 (1�7) - None recorded 33 (63�5) 19 (36�5) 52 (88�1)

Baseline PHQ9

- <4 Minimal 24 (66�7) 12 (33�3) 36 (62�1) - 5-9 Mild 6 (60�0) 4 (40�0) 10 (17�2) - 10-14 Moderate 6 (75�0) 2 (25�0) 8 (13�8) - >=15 Moderately severe/severe 2 (50�0) 2 (50�0) 4 (6�9)

Baseline GAD7

- Minimal 32 (66�7) 16 (33�3) 48 (85�7) - Mild 2 (66�7) 1 (33�3) 3 (5�4) - Moderate or severe 4 (80�0) 1 (20�0) 5 (8�9)

Baseline ASSIST or AUDIT score

- Low 10 (66�7) 5 (33�3) 15 (26�3) - Moderate 20 (66�7) 10 (33�3) 30 (52�6) - High 7 (58�3) 5 (41�7) 12 (21�1)

Baseline risk for adherence issues

Baseline Self-Motivation

- Low risk 2 (66�7) 1 (33�3) 3 (5�1) - Moderate risk 26 (66�7) 13 (33�3) 39 (66�1) - High risk 10 (58�8) 7 (41�2) 17 (28�8)

- Low 3 (60�0) 2 (40�0) 5 (8�8) - Moderate 17 (63�0) 10 (37�0) 27 (47�4) - High 17 (68�0) 8 (32�0) 25 (43�9)

(1) Pearson’s Chi-squared test (2) Fisher’s exact test

p value

0�482 (2)

0�825 (1)

0�831 (1)

0�866 (1)

0�850 (1)

0�904 (1)

MENTAL HEALTH FOLLOW UP DATA

Figures 2 shows the baseline mental health scores for each test, and 2a to 2f shows the patients screening scores over time� The red box displays the median and interquartile range, and the grey shapes display a kernel distribution of the data� AUDIT and ASSIST scores stayed fairly steady, with a median of 9 and 9 at baseline then a slightly higher median of 9�5 and 13�5 at six months and then 4�5 and 15 at 12 months� There is very little data at 18 months thus far� There was a considerable amount of missing data, with only 25 (56�8 %) people having AUDIT or ASSIST scores recorded at 6 months amongst those on treatment at 6 months, and 12(63�2 %) at 12 months of those on treatment at 12 months� Of the 12 with high AUDIT or ASSIST scores at baseline, only 3 have a follow up score at 12 months� Anxiety and depression scores measured with the PHQ9 and GAD7 tools had a median of 2 and 3 at baseline then 2 and 4�5 at six months and 1 and 2 at 12 months� Similarly, there was a considerable amount of missing data�