Patient predictors of poor drug sensitive tuberculosis treatment outcomes in Kyiv Oblast, Ukraine

Omowunmi Aibana; Andrej Slavuckij; Mariya Bachmaha; Viatcheslav Krasiuk; Natasha Rybak; Timothy P. Flanigan; Vasyl Petrenko; Megan B. Murray

doi:10.12688/f1000research.12687.1

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Research Article

Patient predictors of poor drug sensitive tuberculosis treatment outcomes in Kyiv Oblast, Ukraine

[version 1; peer review: 1 approved with reservations, 1 not approved]

Omowunmi Aibana ¹, Andrej Slavuckij², Mariya Bachmaha³, [...] Viatcheslav Krasiuk⁴, Natasha Rybak⁵, Timothy P. Flanigan⁵, Vasyl Petrenko⁴, Megan B. Murray⁶

Omowunmi Aibana ¹, Andrej Slavuckij², [...] Mariya Bachmaha³, Viatcheslav Krasiuk⁴, Natasha Rybak⁵, Timothy P. Flanigan⁵, Vasyl Petrenko⁴, Megan B. Murray⁶

PUBLISHED 23 Oct 2017

Author details Author details

¹ Division of General Internal Medicine, The University of Texas Health Science Center at Houston - McGovern Medical School, Houston, TX, USA
² World Health Organization, Illiyinskaya Street, Kyiv, Ukraine
³ Brown University School of Public Health, Providence, RI, USA
⁴ Department of Pulmonology, Bogomolets National Medical University, Kyiv, Ukraine
⁵ Division of Infectious Diseases, The Miriam Hospital, Warren Alpert Medical School at Brown University, Providence, RI, USA
⁶ Department of Global Health and Social Medicine, Harvard Medical School, Boston, MA, USA

Omowunmi Aibana
Roles: Data Curation, Formal Analysis, Investigation, Validation, Writing – Original Draft Preparation, Writing – Review & Editing

Andrej Slavuckij
Roles: Writing – Original Draft Preparation, Writing – Review & Editing

Mariya Bachmaha
Roles: Investigation, Project Administration, Writing – Review & Editing

Viatcheslav Krasiuk
Roles: Investigation, Writing – Review & Editing

Natasha Rybak
Roles: Project Administration, Writing – Review & Editing

Timothy P. Flanigan
Roles: Funding Acquisition, Supervision, Writing – Review & Editing

Vasyl Petrenko
Roles: Resources, Supervision, Writing – Review & Editing

Megan B. Murray
Roles: Conceptualization, Formal Analysis, Methodology, Supervision, Writing – Original Draft Preparation, Writing – Review & Editing

OPEN PEER REVIEW

REVIEWER STATUS

Abstract

Background: Ukraine has high rates of poor treatment outcomes among drug sensitive tuberculosis (DSTB) patients, while global treatment success rates for DSTB remain high.
We evaluated baseline patient factors as predictors of poor DSTB treatment outcomes.
Methods: We conducted a retrospective analysis of new drug sensitive pulmonary TB patients treated in Kyiv Oblast, Ukraine between November 2012 and October 2014. We defined good treatment outcomes as cure or completion and poor outcomes as death, default or treatment failure. We performed logistic regression analyses, using routine program data, to identify baseline patient factors associated with poor outcomes.
Results: Among 302 patients, 193 (63.9%) experienced good treatment outcomes while 39 (12.9%) failed treatment, 34 (11.3%) died, and 30 (9.9%) defaulted. In the multivariate analysis, HIV positive patients on anti-retroviral therapy (ART) [OR 3.50; 95% CI 1.46 – 8.42; p 0.005] or without ART (OR 4.12; 95% CI 1.36 – 12.43; p 0.01) were at increased risk of poor outcomes. Alcohol abuse (OR 1.81; 95% CI 0.93 - 3.55; p 0.08) and smear positivity (OR 1.75; 95% CI 1.03 - 2.97; p 0.04) were also associated with poor treatment outcomes.
Conclusions: High rates of poor outcomes among patients with newly diagnosed drug sensitive TB in Kyiv Oblast, Ukraine highlight the urgent need for programmatic interventions, especially aimed at patients with the highest risk of poor outcomes.

Keywords

tuberculosis, drug sensitive, treatment outcomes, patient predictors, HIV, HIV-TB coinfection, Ukraine, Eastern Europe

Corresponding author: Omowunmi Aibana

Competing interests: No competing interests were disclosed.

Grant information: Funding support to OA was provided by the National Institute on Drug Abuse training grant T32 DA013911 and the NIH-NIMH grant R25MH83620.
The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Copyright: © 2017 Aibana O et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Data associated with the article are available under the terms of the Creative Commons Zero "No rights reserved" data waiver (CC0 1.0 Public domain dedication).

How to cite: Aibana O, Slavuckij A, Bachmaha M et al. Patient predictors of poor drug sensitive tuberculosis treatment outcomes in Kyiv Oblast, Ukraine [version 1; peer review: 1 approved with reservations, 1 not approved]. F1000Research 2017, 6:1873 (https://doi.org/10.12688/f1000research.12687.1) First published: 23 Oct 2017, 6:1873 (https://doi.org/10.12688/f1000research.12687.1) Latest published: 22 Nov 2019, 6:1873 (https://doi.org/10.12688/f1000research.12687.3)

Introduction

Tuberculosis (TB) control remains challenging worldwide, with approximately 10.4 million new cases diagnosed and 1.8 million TB deaths in 2015¹. Although incidence rates have declined in parts of Eastern Europe, TB continues to be a significant public health problem in many former Soviet Union countries including Ukraine, which currently has the second highest burden of multi-drug resistant TB (MDR-TB) in the WHO European Region after Russia¹. National TB control measures in Ukraine include annual screening with chest radiographs for at risk groups i.e. immunosuppressed patients, diabetics, homeless patients, migrants, incarcerated individuals, and all medical staff in primary healthcare facilities². In addition, surveillance for resistant TB includes routine drug susceptibility testing (DST) for all culture positive isolates; and in 2007 the country adopted WHO recommended directly observed therapy short course (DOTS). However, despite these efforts, Ukraine’s National TB Program (UNTP) still has low treatment success rates. According to the most recent WHO data available for new smear and/or culture positive TB cases in Ukraine, the treatment success rate among these cases was 58% in 2011 in contrast to a global success rate of 83%³.

TB treatment outcomes vary depending on the distribution of risk factors within a treatment cohort, as well as on the quality and nature of TB health services. Patient-related predictors of poor outcome among patients with drug-sensitive TB (DSTB) include HIV, diabetes mellitus (DM), alcohol or substance use, and homelessness^4–10. Health system factors that influence TB outcomes include ease of access to services, diagnostic capabilities, drug availability, social support for patients, and collaboration of TB/HIV services^11,12. Currently, no published research addresses predictors of poor DSTB outcomes in the context of the UNTP, despite the frequency of this outcome. Here, we used routinely collected program data in the Kyiv Oblast of Ukraine to examine the association between baseline patient risk factors and DSTB treatment outcomes. These findings can help develop targeted interventions to address patient populations at the greatest risk of poor outcomes.

Materials and methods

Ethical statement

The study was approved by the Institutional Review Board at The Miriam Hospital, Lifespan, Providence; RI (215014 45CFR 46.110[5]) and the Research Ethics Committee at Bogomolets Medical University in Kyiv, Ukraine. Informed consent was not required because the data were analyzed anonymously, and written informed consent was waived by the Institutional Review Boards.

Setting and study design

We conducted a retrospective chart review to identify baseline risk factors for poor treatment outcomes among drug-sensitive pulmonary TB patients in the Kyiv Oblast of Ukraine, where the notification rate for new pulmonary TB in 2014 was approximately 62 per 100 000 persons. TB diagnosis and management in Kyiv Oblast is provided free of charge and according to Ukraine’s NTP². National guidelines specify that all TB suspects undergo sputum smear microscopy and culture, molecular testing with Xpert^® MTB/RIF and chest X-ray to confirm diagnosis. TB suspects include patients evaluated in primary care settings with complaints of cough, fever, night sweats, weight loss, chest pain, and dyspnea or patients that providers consider at risk for TB based on clinical history. General practitioners then refer suspects to TB specialists for diagnosis and further management. The 2014 UNTP specify the following: baseline susceptibility testing to rifampin (R), isoniazid (H), ethambutol (E), pyrazinamide (Z) and streptomycin (S) on all culture positive TB isolates; baseline screening for pre-specified risk factors including alcohol abuse, intravenous drug use (IVDU), and homelessness (notably, screening for alcohol and substance use relies on patient self-report); baseline HIV testing and provision of anti-retroviral therapy (ART) to those that are positive as soon as possible after initiation of TB treatment; and repeat DST among DSTB patients who are culture positive at three months or at the end of treatment. In Kyiv Oblast, treatment for alcohol or substance abuse is not provided for patients during TB treatment.

UNTP guidelines also specify that DSTB patients receive treatment with two months of RHZE and four months of RH. The previous UNTP guidelines specified inpatient treatment during the intensive phase in specialized TB hospitals, while the subsequent continuation phase occurs in an ambulatory setting. Dedicated adult TB hospitals exist in each administrative region of Ukraine where patients receive testing and treatment. Although latest national guidelines in 2014 now recommend outpatient management of DSTB², many regions in Ukraine, including Kyiv Oblast, have yet to implement this practice and continue to hospitalize patients during the intensive phase.

For newly diagnosed patients with HIV, ART is initiated during hospitalization and after discharge, HIV-related care occurs at HIV programs that are distinct from the TB clinics, which provide outpatient TB care. Standard ART regimen for co-infected patients include Tenofovir, Lamivudine, and Efavirenz. In Kyiv Oblast, outpatients may receive daily directly observed therapy or receive a supply of medication at 7 – 10 day intervals. Clinicians can continue the inpatient care of individuals at high risk for default (e.g. homeless patients) for the entire treatment duration, although compliance is not enforced; and patients are free to leave the hospital any time. UNTP guidelines also recommend follow up for DSTB patients at yearly intervals for three years after treatment completion.

Data collection and statistical analysis

We analyzed routinely collected clinical and programmatic data from the three TB hospitals in Kyiv Oblast, which together admit approximately 1100 patients annually for pulmonary TB. We included all adult patients (≥ 16 years) treated for newly diagnosed drug-sensitive pulmonary TB between November 2012 and October 2014. We excluded patients who did not yet have a treatment outcome assigned because they were undergoing the initial course of TB treatment at the time of data extraction in November 2014, and those with previous TB history.

We extracted the following information routinely collected by the TB program in an electronic database: age, gender, residence, employment status, history of TB contact, homelessness, immigration status, previous incarceration, HIV status with ART initiation dates, history of alcohol abuse and intravenous (IV) drug use, as well as mode of case finding (active or passive); passive TB case finding refers to the diagnosis of TB among patients who self-initiate contact with healthcare providers for management of TB symptoms. We also recorded baseline sputum smear, culture and DST results. The NTP provides standardized paper forms used by TB providers to record all baseline demographic and clinical information for routine program monitoring. In Kyiv Oblast TB hospitals, all data are subsequently entered in an electronic database by the statistics department.

Treatment outcomes for DSTB are classified in Kyiv Oblast according to WHO guidelines¹³. Good treatment outcomes include cure and treatment completion, while poor outcomes include deaths, default and treatment failure. The WHO considers a DSTB patient cured if he or she remains smear or culture negative in the last month of treatment and on at least one previous occasion. A patient is considered to have completed treatment if he or she has received a full course of therapy but has not received smear or culture in the last month of treatment. Any deaths during TB treatment are considered TB related. A patient is considered to have defaulted if he or she interrupts treatment for two or more consecutive months. Patients who remain smear or culture positive at month 5 or later during treatment are considered treatment failures; and in Kyiv Oblast patients who acquire resistance are also categorized as treatment failures. The exact dates of treatment outcomes or last follow up visits were not captured in the database.

We analyzed only patients with confirmed drug sensitive pulmonary TB, and we excluded from the analysis patients who transferred out or had missing outcomes. We did not follow up with patients in the community to ascertain treatment outcome among those with missing data on final outcome. We compared categorical variables with Fisher’s exact test and continuous variables with the Wilcoxon rank sum test. We performed univariate and multivariate logistic regression analyses to identify baseline predictors of combined poor treatment outcomes. For the multivariate model, we included baseline variables previously known to be associated with poor outcomes (age, sex, HIV, alcohol abuse, homelessness) and any variable associated with poor outcomes at p value less than 0.2 in the univariate analysis. We further evaluated baseline predictors for the outcomes of death and treatment failure separately. We used complete case analysis in the regression models. We used the regression coefficients specified by the final multivariate model to predict probability of combined poor outcomes. Data were analyzed using SAS v9.4 (SAS Institute, Cary, NC 2013).

Results

We identified 561 patients treated for new DSTB between November 2012 and October 2014. Among them, we excluded 99 (17.6%) patients who did not yet have a treatment outcome because they were still undergoing TB treatment at the time of analysis (Figure 1). Table 1 lists baseline characteristics of the remaining 462 patients; among them, 122 (26.4%) patients had no drug susceptibility testing performed. 340 patients (73.6%) had a baseline DST to confirm drug sensitive pulmonary TB, and 181 (39.2%) underwent Xpert/Rif testing at baseline. 75 (16.2%) patients tested HIV positive, while HIV status was not recorded for 8 (1.7%) patients. Among the HIV positive patients, 34 (45.3%) were initiated on ART during TB treatment. Median time to ART initiation from TB treatment start date was 43.5 days (IQR 34.0 – 59.5).

Figure 1. Flow diagram of drug sensitive pulmonary TB cases analyzed.

Table 1. Baseline characteristics of drug-sensitive tuberculosis patients in Kyiv Oblast (November 2012 to October 2014, N = 462).

IQR: Interquartile Range.

	N (%) or median (IQR)
Age	40.0 (33.0 – 52.0)
Male	351 (76.0)
HIV status
Negative	379 (82.0)
Positive	75 (16.2)
Unknown	8 (1.7)
Initiated on ART among HIV positive	34 (45.3)
Median days to ART initiation	43.5 (34.0 – 59.5)
Rural residence^a	246 (58.9)
Alcohol abuse	69 (14.9)
Intravenous drug use (IVDU)	6 (1.3)
Known TB contact at diagnosis	4 (0.9)
Homeless	11 (2.4)
Unemployed	256 (55.4)
Migrant from outside Kyiv Oblast	1 (0.2)
Previous Incarceration	7 (1.5)
Passive Case finding^b	377 (81.9)
Smear Positive at baseline^c	242 (52.6)
Have baseline Drug Susceptibility Test (DST) result	340 (73.6)
Have baseline Xpert/RIF Result	181 (39.2)

^a N = 418

^b N = 461

^c N = 460

Of the 340 patients with DST results, 38 (11.2%) had missing outcome data. Among the remaining 302 patients, 104 (34.4%) experienced treatment cure and 89 (29.5%) completed treatment, while 39 (12.9%) failed treatment, 34 (11.3%) died, 30 (9.9%) defaulted, and 6 (2.0%) transferred out.

In the univariate analysis, significant baseline predictors of poor treatment outcomes included alcohol abuse (OR 1.95; 95% CI 1.05 - 3.61; p 0.03), and smear positive disease (OR 1.70; 95% CI 1.04 - 2.75; p 0.03) (Table 2). Compared to HIV negative, HIV patients were also at increased risk of poor outcomes; those who were not initiated on ART were four times as likely to experience poor outcomes (OR 4.07; 95% CI 1.45 – 11.39; p 0.01), while patients on ART were more than twice as likely to have a poor treatment outcome (OR 2.58; 95% CI 1.14 – 5.85; p 0.02). Homeless patients were also at increased risk of poor outcomes, although this association was not significant at the .05 level (OR 7.76; 95% CI 0.86 – 70.32). Unemployment (OR 1.59; 95% CI 0.97 – 2.61; p 0.06) and passive case finding (OR 1.78; 95% CI 0.94 – 3.39; p 0.07) also conferred borderline significantly increased risk of poor treatment outcomes in the univariate analysis. Time to ART initiation was not associated with poor outcomes (OR 1.02; 95% CI 0.98 – 1.06; p 0.33) (Table 2).

Table 2. Univariate and multivariate analyses of baseline predictors of combined poor outcomes among drug-sensitive TB patients.

OR: Odds Ratio.

	Univariate Model (N = 296)^a		Multivariate Model (N = 292)
	OR (95% CI)	p value	Adjusted Odds Ratio^b (95% CI)	p value
Age	1.01 (0.99 – 1.02)	0.48	1.01 (0.99 – 1.03)	0.18
Male	1.12 (0.63 – 1.99)	0.70	1.24 (0.66 – 2.34)	0.50
HIV negative^c	Ref		Ref
HIV positive with ART	2.58 (1.14 – 5.85)	0.02	3.50 (1.46 – 8.42)	0.005
HIV positive without ART	4.07 (1.45 – 11.39)	0.01	4.12 (1.36 – 12.43)	0.01
Time to ART initiation^d	1.02 (0.98 – 1.06)	0.33	NA
Alcohol abuse	1.95 (1.05 – 3.61)	0.03	1.81 (0.93 – 3.55)	0.08
Homeless	7.76 (0.86 – 70.32)	0.07	6.38 (0.69 – 59.40)	0.10
Smear positive^c	1.70 (1.04 – 2.75)	0.03	1.75 (1.03 – 2.97)	0.04
Rural^e	1.23 (0.73 – 2.07)	0.42	NA
Unemployed	1.59 (0.97 – 2.61)	0.06	1.26 (0.72 – 2.20)	0.43
TB contact	5.76 (0.59 – 56.05)	0.13	NA^f
Passive case finding	1.78 (0.94 – 3.39)	0.07	1.18 (0.60 – 2.35)	0.63

^a Patients with confirmed drug sensitive TB and outcomes of cure, completion, death, treatment failure and default.

^b Adjusted for age, gender, HIV, alcohol abuse, homelessness, baseline smear status, unemployment and passive case finding.

^c N = 294

^d N = 26

^e N = 269

^f Excluded from multivariate analysis because only 4 patients had known TB contact.

When we adjusted for other risk factors, we found that smear positivity (OR 1.75; 95% CI 1.03 - 2.97; p 0.04) and HIV positivity (on ART [OR 3.50; 95% CI 1.46 – 8.42; p 0.005] and without ART [OR 4.12; 95% CI 1.36 – 12.43; p 0.01]) all remained significant predictors of poor outcome. Patients with alcohol abuse also had a modest increase in risk of poor outcomes (OR 1.81; 95% CI 0.93 – 3.55; p 0.08) and the odds of poor outcomes among the homeless continued to be high but not statistically significant at 6.38 (95% CI 0.69 – 59.40) (Table 2). Unemployment (OR 1.26; 95% CI 0.72 – 2.20; p 0.43) and passive case finding (OR 1.18; 95% CI 0.60 – 2.35; p 0.63) were no longer associated with increased risk of poor outcomes in the adjusted analysis (Table 2). Our multivariate model predicted that a 40-year-old male who is HIV positive but not on ART, with alcohol abuse and smear positive disease, has a 75.8% probability of poor treatment outcome.

When we separately evaluated risk factors for death during DSTB treatment, in the adjusted analysis, we found age (OR 1.03; 95% CI 1.00 – 1.06; p 0.03), HIV positivity (OR 4.21; 95% CI 1.44 – 12.30; p 0.01) and alcohol abuse (OR 2.54; 95% CI 1.00 – 6.42; p 0.05) were associated with statistically significant increased risk of death (Table 3). HIV positivity (OR 7.42; 95% CI 2.56 – 21.54; p < 0.001) and smear positive disease at baseline (OR 4.99; 95% CI 2.00 – 12.45; p 0.001) were the strongest predictors of DSTB treatment failure (Table 4).

Table 3. Univariate and multivariate analyses of baseline predictors of death among drug-sensitive TB patients.

OR: Odds Ratio.

	Univariate Model (N = 227)^a		Multivariate Model (N = 224)
	OR (95% CI)	p value	Adjusted Odds Ratio^b (95% CI)	p value
Age	1.02 (1.00 – 1.05)	0.05	1.03 (1.00 – 1.06)	0.03
Male	0.85 (0.37 – 1.94)	0.69	1.05 (0.42 – 2.63)	0.91
HIV positive^c	2.96 (1.17 – 7.49)	0.02	4.21 (1.44 – 12.30)	0.01
Alcohol abuse	2.31 (0.97 – 5.50)	0.06	2.54 (1.00 – 6.42)	0.05
Homeless	12.00 (1.06 – 136.23)	0.05	NA^d
Smear positive^e	1.84 (0.88 – 3.85)	0.11	1.80 (0.81 – 3.98)	0.15
Rural^f	1.35 (0.60 – 3.06)	0.47	NA
Unemployed	1.38 (0.66 – 2.92)	0.40	NA
TB contact	5.82 (0.36 – 95.42)	0.22	NA
Passive case finding	10.03 (1.34 – 75.43)	0.03	7.04 (0.91 – 54.15)	0.06

^a Patients with confirmed drug sensitive TB and outcomes of cure, completion and death.

^b Adjusted for age, gender, HIV, alcohol abuse, baseline smear status, and passive case finding.

^c N = 225

^d Excluded from multivariate analysis because there were only 3 homeless patients.

^e N = 226

^f N = 206

Table 4. Univariate and multivariate analyses of baseline predictors of treatment failure among drug-sensitive TB patients.

OR: Odds Ratio.

	Univariate Model (N = 232)^a		Multivariate Model (N = 228)
	OR (95% CI)	p value	Adjusted Odds Ratio^b (95% CI)	p value
Age	0.99 (0.97 – 1.02)	0.47	0.99 (0.96 – 1.03)	0.70
Male	2.07 (0.76 – 5.60)	0.15	2.27 (0.77 – 6.69)	0.14
HIV positive^c	4.27 (1.85 – 9.85)	0.001	7.42 (2.56 – 21.54)	<0.001
Alcohol abuse	0.95 (0.34 – 2.63)	0.91	0.90 (0.30 – 2.72)	0.86
Homeless	10.38 (0.92 – 117.41)	0.06	NA^d
Smear positive^c	2.79 (1.33 – 5.85)	0.01	4.99 (2.00 – 12.45)	0.001
Rural^e	0.90 (0.43 – 1.88)	0.78	NA
Unemployed	1.37 (0.68 – 2.77)	0.38	NA
TB contact	10.38 (0.92 – 117.41)	0.06	NA^d
Passive case finding	2.07 (0.76 – 5.60)	0.15	1.44 (0.50 – 4.13)	0.50

^a Patients with confirmed drug sensitive TB and outcomes of cure, completion and treatment failure.

^b Adjusted for age, gender, HIV, alcohol abuse, baseline smear status, and passive case finding.

^c N = 230

^d Excluded from multivariate analysis because there were only 3 homeless patients and 3 patients with known TB contact.

^e N = 211

Outcome	Sex	Age_Category	Residence	Case_finding	Alcohol	IVDU	TB_contact	Homeless	Unemployed	Migrant	Prev_incarceration	HIV_status	dst	art	time_to_ART	smear	xpert
Cured	Male	≤25	rural	Passive	No	No	No	No	No	No	No	Negative	yes	hiv_neg		pos	yes
On treatment	Male	≤25	urban	Active	No	No	No	No	No	No	No	Negative	yes	hiv_neg		pos	yes
Cured	Female	≤25	urban	Passive	No	No	No	No	Yes	No	No	Negative	yes	hiv_neg		neg	yes
Completed	Male	≤25	urban	Passive	No	No	No	No	No	No	No	Negative	yes	hiv_neg		neg	no
Cured	Female	≤25	urban	Passive	No	No	No	No	No	No	No	Negative	yes	hiv_neg		pos	no
Cured	Female	≤25	rural	Active	No	No	No	No	No	No	No	Negative	yes	hiv_neg		neg	no
Cured	Female	≤25	urban	Passive	No	No	No	No	No	No	No	Negative	no	hiv_neg		pos	yes
Completed	Female	≤25	urban	Active	No	No	No	No	No	No	No	Negative	yes	hiv_neg		neg	no
Cured	Male	≤25	rural	Active	No	No	No	No	No	No	No	Negative	yes	hiv_neg		pos	yes
Cured	Female	≤25	urban	Passive	No	No	No	No	No	No	No	Negative	no	hiv_neg		neg	no
Cured	Male	≤25	rural	Active	No	No	No	No	Yes	No	No	Negative	yes	hiv_neg		pos	no
Died	Female	≤25	rural	Passive	No	No	No	No	Yes	No	No	Negative	yes	hiv_neg		neg	no
Default	Female	≤25	urban	Passive	No	No	No	No	Yes	No	No	Negative	no	hiv_neg		pos	no
Failure	Male	≤25	urban	Passive	No	No	No	No	No	No	No	Negative	yes	hiv_neg		neg	no
Cured	Male	≤25	urban	Active	No	No	No	No	No	No	No	Negative	yes	hiv_neg		neg	no
Cured	Male	≤25		Passive	No	No	No	No	Yes	No	No	Negative	yes	hiv_neg		neg	no
Cured	Male	≤25		Passive	No	No	No	No	Yes	No	No	Negative	yes	hiv_neg		pos	yes
Cured	Male	≤25	rural	Passive	No	No	No	No	No	No	No	Negative	no	hiv_neg		pos	no
Completed	Male	≤25	urban	Passive	No	No	No	No	No	No	No	Negative	yes	hiv_neg		neg	no
Cured	Female	≤25	urban	Passive	Yes	No	No	No	Yes	No	No	Positive	yes	no		neg	no
Cured	Female	≤25	rural	Passive	No	No	No	No	Yes	No	No	Negative	yes	hiv_neg		neg	no
On treatment	Male	≤25	urban	Passive	No	No	No	No	No	No	No	Negative	yes	hiv_neg		neg	no
Cured	Male	≤25	rural	Passive	No	No	No	No	Yes	No	No	Positive	yes	yes	34	neg	no
Cured	Male	≤25	rural	Passive	No	No	No	No	No	No	No	Negative	no	hiv_neg		neg	no
Failure	Female	≤25	rural	Passive	No	No	No	No	No	No	No	Positive	yes	yes	33	pos	no
Default	Male	≤25	rural	Passive	No	No	No	No	No	No	No	Negative	yes	hiv_neg		neg	yes
Default	Male	≤25	rural	Passive	Yes	No	No	No	Yes	No	No	Negative	yes	hiv_neg		neg	yes
Cured	Male	≤25	rural	Passive	No	No	No	No	No	No	No	Negative	yes	hiv_neg		neg	no
Default	Male	≤25	urban	Passive	No	No	No	No	No	No	No	Negative	no	hiv_neg		pos	yes
Cured	Male	≤25	rural	Passive	No	No	No	No	No	No	No	Negative	yes	hiv_neg		pos	no
On treatment	Male	≤25	rural	Passive	No	No	No	No	No	No	No	Negative	yes	hiv_neg		neg	no
Failure	Male	≤25	rural	Passive	Yes	No	Yes	No	Yes	No	No	Negative	yes	hiv_neg		pos	no
Completed	Male	≤25	rural	Passive	No	No	No	No	Yes	No	No	Negative	yes	hiv_neg		pos	no
Default	Male	≤25	urban	Passive	Yes	No	No	No	Yes	No	Yes	Negative	no	hiv_neg		neg	no
Cured	Male	≤25	urban	Passive	No	No	No	No	No	No	No	Negative	no	hiv_neg		neg	no
Completed	Male	≤25	urban	Passive	No	No	No	No	No	No	No		yes			neg	no
Failure	Male	≤25	urban	Passive	No	No	No	Yes	Yes	No	No	Negative	yes	hiv_neg		pos	no
Cured	Male	≤25	urban	Passive	No	No	No	No	Yes	No	No	Negative	no	hiv_neg		pos	no
On treatment	Male	≤25	urban	Passive	No	No	No	No	No	No	No	Negative	yes	hiv_neg		neg	no
Completed	Male	26-45	rural	Passive	No	No	No	No	Yes	No	No	Negative	yes	hiv_neg		pos	no
Died	Female	26-45	rural	Passive	No	No	No	No	No	No	No	Positive	no	no		pos	no
Default	Female	26-45	rural	Passive	Yes	No	No	No	Yes	No	No	Positive	yes	yes	34	neg	no
Cured	Female	26-45		Active	No	No	No	No	No	No	No	Negative	yes	hiv_neg		neg	no
Cured	Female	26-45	urban	Passive	No	No	No	No	Yes	No	No	Negative	yes	hiv_neg		pos	no
Cured	Male	26-45	urban	Passive	No	No	No	No	Yes	No	No	Negative	yes	hiv_neg		neg	yes
Cured	Female	26-45	urban	Passive	No	No	No	No	No	No	No	Negative	yes	hiv_neg		pos	no
Completed	Male	26-45	rural	Passive	No	No	No	No	No	No	No	Negative	yes	hiv_neg		neg	yes
Completed	Male	26-45		Passive	No	No	No	No	No	No	No	Negative	yes	hiv_neg		neg	no
Default	Male	26-45	urban	Active	No	No	No	No	No	No	No	Negative	yes	hiv_neg		neg	yes
Cured	Male	26-45	urban	Passive	No	No	No	No	Yes	No	No	Negative	yes	hiv_neg		neg	no
Cured	Female	26-45	urban	Passive	No	No	No	No	Yes	No	No	Negative	no	hiv_neg		pos	no
Failure	Male	26-45	rural	Passive	No	No	No	No	Yes	No	No	Negative	no	hiv_neg		pos	yes
Completed	Male	26-45	rural	Passive	No	No	No	No	Yes	No	No	Negative	no	hiv_neg		neg	yes
Completed	Female	26-45	rural	Active	No	No	No	No	No	No	No	Negative	yes	hiv_neg		neg	no
Cured	Male	26-45	rural	Passive	No	No	Yes	No	No	No	No	Negative	yes	hiv_neg		pos	yes
Completed	Male	26-45	rural	Passive	No	No	No	No	Yes	No	No	Negative	yes	hiv_neg		neg	no
Cured	Male	26-45	rural	Passive	No	No	No	No	No	No	No	Negative	yes	hiv_neg		neg	no
Completed	Male	26-45	urban	Active	No	No	No	No	Yes	No	No	Negative	yes	hiv_neg		neg	yes
Default	Male	26-45	urban	Passive	No	No	No	No	No	No	No	Positive	no	no		neg	yes
Completed	Male	26-45	rural	Active	No	No	No	No	Yes	No	No	Negative	yes	hiv_neg		neg	no
Cured	Male	26-45	urban	Passive	No	No	No	No	Yes	No	No	Negative	no	hiv_neg		pos	no
Completed	Male	26-45	rural	Passive	No	No	No	No	Yes	No	No	Positive	yes	yes	35	neg	no
Cured	Male	26-45	urban	Active	Yes	No	No	No	No	No	Yes	Negative	yes	hiv_neg		pos	no
Failure	Male	26-45	urban	Passive	No	No	No	No	Yes	No	No	Negative	no	hiv_neg		pos	yes
Cured	Male	26-45	urban	Active	No	No	No	No	Yes	No	No	Negative	no	hiv_neg		neg	yes
Failure	Male	26-45	rural	Passive	Yes	No	No	No	Yes	No	No	Negative	yes	hiv_neg		neg	yes
On treatment	Male	26-45	rural	Passive	No	No	No	No	No	No	No	Negative	yes	hiv_neg		neg	no
Default	Female	26-45	urban	Passive	Yes	No	No	No	Yes	No	No	Positive	yes	no		pos	yes
Cured	Male	26-45	rural	Passive	No	No	No	No	No	No	No	Negative	yes	hiv_neg		neg	no
Cured	Male	26-45	urban	Active	No	No	No	No	Yes	No	No	Negative	yes	hiv_neg		neg	no
Cured	Male	26-45	urban	Active	No	No	No	No	No	No	No	Negative	yes	hiv_neg		pos	no
Completed	Male	26-45	rural	Active	No	No	No	No	Yes	No	No	Negative	yes	hiv_neg		neg	no
Cured	Male	26-45	rural	Passive	No	No	No	No	No	No	No	Negative	no	hiv_neg		neg	no
Cured	Female	26-45	rural	Passive	No	No	No	No	No	No	No	Negative	yes	hiv_neg		neg	yes
On treatment	Male	26-45	rural	Passive	No	No	No	No	No	No	No	Negative	yes	hiv_neg		neg	yes
Transfer out	Male	26-45	rural	Passive	No	Yes	No	No	Yes	No	No	Positive	no	yes	43	neg	yes
Completed	Male	26-45	rural	Active	No	No	No	No	No	No	No	Negative	yes	hiv_neg		neg	no
Completed	Male	26-45	rural	Passive	No	No	No	No	Yes	No	No	Negative	yes	hiv_neg		neg	no
Cured	Female	26-45	rural	Active	Yes	No	No	No	Yes	No	No	Negative	yes	hiv_neg		pos	no
Cured	Male	26-45	rural	Passive	No	No	No	No	No	No	No	Negative	no	hiv_neg		pos	no
Completed	Male	26-45	urban	Active	No	No	No	No	No	No	No	Negative	yes	hiv_neg		neg	no
Failure	Female	26-45	rural	Passive	Yes	No	No	No	No	No	No	Positive	yes	yes	44	neg	yes
Cured	Male	26-45	rural	Active	No	No	No	No	Yes	No	No	Positive	yes	yes	45	neg	yes
Completed	Male	26-45	urban	Active	No	No	No	No	No	No	No	Negative	yes	hiv_neg		neg	no
On treatment	Female	26-45	rural	Active	No	No	No	No	No	No	No	Negative	yes	hiv_neg		neg	yes
Cured	Male	26-45	rural	Passive	No	No	No	No	Yes	No	No	Negative	yes	hiv_neg		neg	yes
Completed	Male	26-45	rural	Passive	No	No	No	No	No	No	No	Negative	yes	hiv_neg		pos	no
Failure	Male	26-45	rural	Passive	No	No	No	No	No	No	No	Negative	yes	hiv_neg		pos	no
Completed	Male	26-45	urban	Passive	No	No	No	No	Yes	Yes	No	Positive	yes	no		neg	no
Cured	Male	26-45	rural	Passive	No	Yes	No	No	Yes	No	No	Positive	no	yes		neg	no
Completed	Female	26-45	urban	Active	No	No	No	No	Yes	No	No	Negative	yes	hiv_neg		neg	no
Completed	Male	26-45	urban	Passive	No	No	No	No	Yes	No	No	Negative	yes	hiv_neg		pos	yes
Died	Male	26-45	urban	Passive	No	No	No	No	No	No	No	Positive	yes	yes	53	neg	yes
Died	Male	26-45	rural	Passive	No	No	No	No	Yes	No	No	Negative	yes	hiv_neg		pos	no
Failure	Female	26-45	urban	Passive	No	No	No	No	Yes	No	No	Positive	no	yes	110	pos	no
Transfer out	Male	26-45	rural	Passive	No	No	No	No	Yes	No	No	Negative	yes	hiv_neg		neg	no
Died	Male	26-45	urban	Passive	No	No	No	No	Yes	No	No	Negative	yes	hiv_neg		pos	no
On treatment	Male	26-45	rural	Passive	No	No	No	Yes	No	No	No	Positive	yes	no		pos	no
Failure	Male	26-45	rural	Passive	No	No	No	No	Yes	No	No	Negative	no	hiv_neg		pos	yes
On treatment	Female	26-45	rural	Passive	No	No	No	No	No	No	No	Negative	yes	hiv_neg		pos	no
Failure	Male	26-45	urban	Passive	No	No	No	No	Yes	No	No	Negative	yes	hiv_neg		pos	yes
Died	Male	26-45	rural	Passive	No	No	No	No	Yes	No	No		no			pos	yes
Completed	Male	26-45	urban	Passive	No	No	No	No	Yes	No	Yes	Positive	yes	no		neg	no
On treatment	Male	26-45	rural	Passive	No	No	No	No	No	No	No	Negative	yes	hiv_neg		pos	no
Cured	Female	26-45	urban	Passive	No	No	No	No	No	No	No	Negative	no	hiv_neg		pos	yes
On treatment	Female	26-45	urban	Active	No	No	No	No	Yes	No	No	Negative	yes	hiv_neg		neg	no
Failure	Male	26-45	urban	Passive	No	No	No	No	Yes	No	No	Positive	yes	yes	53	neg	no
Cured	Male	26-45	rural	Passive	Yes	No	No	No	Yes	No	No	Negative	yes	hiv_neg		neg	no
Completed	Male	26-45	rural	Passive	No	No	No	No	No	No	No	Negative	yes	hiv_neg		pos	yes
Failure	Male	26-45	rural	Active	No	No	No	No	Yes	No	No	Negative	yes	hiv_neg		pos	yes
On treatment	Male	26-45	rural	Active	No	No	No	No	No	No	No	Negative	yes	hiv_neg		neg	yes
On treatment	Male	26-45	rural	Passive	Yes	No	No	No	Yes	No	No	Negative	yes	hiv_neg		pos	yes
On treatment	Male	26-45	rural	Passive	No	No	No	No	Yes	No	No	Positive	yes	yes	56	neg	yes
On treatment	Male	26-45	rural	Active	No	No	No	No	Yes	No	No	Positive	yes	yes	51	pos	yes
Failure	Male	26-45	urban	Passive	No	No	No	No	No	No	No	Positive	yes	yes		neg	yes
Cured	Female	26-45	urban	Active	No	No	No	No	No	No	No	Negative	yes	hiv_neg		neg	no
Completed	Male	26-45		Passive	No	No	No	No	No	No	No	Negative	no	hiv_neg		neg	no
Completed	Male	26-45	rural	Active	No	No	No	No	No	No	No	Negative	no	hiv_neg		neg	no
Completed	Male	26-45		Active	No	No	No	No	No	No	No		no			neg	no
Completed	Male	26-45	rural	Passive	No	No	No	No	Yes	No	No	Negative	no	hiv_neg		neg	no
Completed	Female	26-45	urban	Passive	Yes	No	No	No	Yes	No	No	Negative	yes	hiv_neg		pos	yes
Completed	Male	26-45	rural	Passive	Yes	No	No	No	Yes	No	No	Negative	yes	hiv_neg		neg	yes
Failure	Male	26-45	urban	Passive	No	No	No	No	Yes	No	No	Negative	no	hiv_neg		pos	no
Cured	Male	26-45	urban	Passive	No	No	No	No	Yes	No	No	Positive	yes	yes	60	neg	yes
Default	Male	26-45	urban	Passive	No	No	No	No	Yes	No	No	Negative	yes	hiv_neg		pos	yes
Died	Female	26-45	urban	Active	Yes	No	No	No	Yes	No	No	Negative	yes	hiv_neg		neg	no
Cured	Male	26-45	rural	Passive	No	No	No	No	No	No	No	Negative	yes	hiv_neg		neg	yes
Cured	Male	26-45		Passive	No	No	No	No	Yes	No	No	Negative	yes	hiv_neg		pos	yes
Failure	Male	26-45		Passive	No	No	No	No	Yes	No	No	Positive	no	no		neg	yes
Cured	Male	26-45	urban	Passive	No	No	No	No	No	No	No	Negative	yes	hiv_neg		pos	yes
Failure	Male	26-45	rural	Passive	No	No	No	No	No	No	No	Positive	yes	yes	63	pos	yes
Cured	Female	26-45	rural	Passive	Yes	No	No	No	Yes	No	No	Negative	yes	hiv_neg		pos	yes
Cured	Male	26-45	urban	Passive	No	No	No	No	Yes	No	No	Negative	no	hiv_neg		neg	yes
Completed	Male	26-45	rural	Passive	Yes	No	No	No	Yes	No	No	Negative	yes	hiv_neg		pos	yes
Died	Female	26-45	urban	Passive	No	No	No	No	Yes	No	No	Positive	yes	no		pos	no
Completed	Male	26-45	urban	Active	No	No	No	No	Yes	No	No	Negative	yes	hiv_neg		pos	no
Died	Male	26-45	rural	Passive	No	No	No	No	Yes	No	No	Positive	no	no		pos	no
Cured	Male	26-45	rural	Passive	No	No	No	No	Yes	No	No	Positive	yes	yes	38	neg	no
Completed	Male	26-45	urban	Passive	No	No	No	No	No	No	No	Negative	yes	hiv_neg		pos	no
Completed	Female	26-45	rural	Passive	No	No	No	No	No	No	No	Negative	yes	hiv_neg		neg	yes
Cured	Male	26-45	rural	Passive	No	No	No	No	Yes	No	No	Positive	yes	yes	29	neg	no
Died	Female	26-45	rural	Passive	Yes	No	No	No	Yes	No	No	Positive	yes	no		neg	yes
On treatment	Male	26-45	urban	Passive	No	No	No	No	Yes	No	No	Negative	yes	hiv_neg		pos	yes
Cured	Male	26-45	rural	Passive	No	No	No	No	No	No	No	Positive	yes	no		neg	no
Cured	Female	26-45	rural	Passive	No	No	No	No	Yes	No	No	Negative	yes	hiv_neg		pos	no
Died	Female	26-45	rural	Passive	No	No	No	No	No	No	No		no			pos	no
Completed	Male	26-45	rural	Passive	No	No	No	No	No	No	No	Negative	yes	hiv_neg		neg	no
Failure	Male	26-45		Active	No	No	No	No	Yes	No	No	Positive	yes	yes	32	neg	yes
Died	Male	26-45		Passive	No	No	No	No	No	No	No	Negative	yes	hiv_neg		neg	yes
Default	Male	26-45	urban	Passive	No	No	No	No	Yes	No	No	Positive	yes	no		neg	yes
Transfer out	Male	26-45	rural	Passive	No	No	No	No	Yes	No	No		yes			neg	no
Completed	Male	26-45	rural	Active	No	No	No	No	Yes	No	No	Negative	yes	hiv_neg		neg	no
Cured	Male	26-45	urban	Passive	No	No	No	No	No	No	No	Positive	no	yes	55	neg	no
Cured	Male	26-45		Passive	No	No	No	No	Yes	No	Yes	Negative	yes	hiv_neg		pos	no
Completed	Male	26-45	urban	Active	Yes	No	No	No	Yes	No	No	Negative	yes	hiv_neg		neg	no
Cured	Female	26-45	urban	Passive	No	No	No	No	No	No	No	Negative	yes	hiv_neg		pos	no
Default	Male	26-45	rural	Passive	No	No	No	No	Yes	No	No	Negative	no	hiv_neg		pos	yes
Default	Male	26-45	urban	Active	No	No	No	No	No	No	No	Negative	no	hiv_neg		neg	yes
Default	Male	26-45	rural	Passive	No	Yes	No	No	Yes	No	No	Positive	yes	no		neg	yes
Cured	Male	26-45		Passive	No	No	No	No	Yes	No	No	Negative	yes	hiv_neg		neg	no
Cured	Male	26-45		Passive	No	No	No	No	No	No	No	Positive	yes	yes	41	pos	no
Completed	Male	26-45	urban	Active	No	No	No	No	Yes	No	No	Negative	yes	hiv_neg		pos	no
Cured	Female	26-45		Passive	No	No	No	No	No	No	No	Negative	no	hiv_neg		pos	no
Failure	Male	26-45	rural	Passive	Yes	No	No	No	Yes	No	No	Negative	yes	hiv_neg		pos	no
Failure	Male	26-45	rural	Passive	Yes	No	No	No	Yes	No	No	Positive	no	no		pos	yes
Died	Male	26-45		Passive	No	No	No	No	No	No	No	Negative	yes	hiv_neg		neg	yes
Cured	Male	26-45	urban	Passive	No	Yes	No	No	Yes	No	Yes	Negative	no	hiv_neg		neg	yes
On treatment	Male	26-45	urban	Active	No	No	No	No	No	No	No	Negative	yes	hiv_neg		neg	no
Died	Male	26-45	rural	Passive	No	No	No	No	Yes	No	No	Negative	no	hiv_neg		pos	no
Completed	Male	26-45	rural	Passive	No	No	No	No	Yes	No	No	Negative	yes	hiv_neg		pos	no
Completed	Male	26-45	rural	Passive	No	No	No	No	No	No	No	Positive	yes	yes	26	neg	no
Completed	Male	26-45	urban	Active	No	No	No	No	Yes	No	No	Positive	no	no		neg	no
Died	Male	26-45	rural	Passive	Yes	No	No	No	Yes	No	No	Negative	yes	hiv_neg		neg	yes
Cured	Female	26-45	rural	Passive	No	No	No	No	Yes	No	No	Positive	no	no		pos	yes
Died	Male	26-45	rural	Passive	No	No	No	No	Yes	No	No	Positive	yes	no		pos	yes
Died	Female	26-45	urban	Passive	No	No	No	No	No	No	No	Positive	no	no		pos	no
Died	Male	26-45	urban	Passive	No	No	No	No	No	No	No	Positive	yes	no		pos	yes
Failure	Male	26-45		Passive	No	No	No	No	No	No	No	Negative	no	hiv_neg		pos	yes
Died	Male	26-45		Passive	Yes	No	No	No	Yes	No	No	Negative	no	hiv_neg		pos	yes
Default	Male	26-45	urban	Passive	No	No	No	No	Yes	No	No	Positive	yes	yes	36	pos	yes
Cured	Male	26-45	urban	Passive	No	No	No	No	Yes	No	No	Positive	yes	no		neg	no
Failure	Male	26-45	urban	Active	No	No	No	No	Yes	No	No	Negative	yes	hiv_neg		pos	no
Cured	Male	26-45	urban	Passive	No	No	No	No	Yes	No	No	Negative	yes	hiv_neg		neg	no
Completed	Male	26-45	rural	Passive	No	No	No	No	No	No	No	Negative	yes	hiv_neg		pos	yes
Failure	Male	26-45	rural	Passive	No	No	No	No	No	No	No	Negative	yes	hiv_neg		pos	yes
Cured	Male	26-45	urban	Passive	No	No	No	No	Yes	No	No	Negative	yes	hiv_neg		neg	yes
Failure	Male	26-45	rural	Passive	No	No	No	No	No	No	No	Negative	yes	hiv_neg		pos	no
Default	Female	26-45	urban	Passive	No	No	No	No	Yes	No	No	Negative	no	hiv_neg		pos	yes
Cured	Male	26-45	rural	Passive	No	No	No	No	No	No	No	Negative	yes	hiv_neg		neg	yes
Failure	Male	26-45	rural	Passive	No	No	No	No	Yes	No	No	Negative	no	hiv_neg		pos	no
Completed	Male	26-45	rural	Passive	No	No	No	No	No	No	No	Negative	yes	hiv_neg		pos	no
Cured	Male	26-45	rural	Passive	No	No	No	No	No	No	No	Negative	no	hiv_neg		pos	no
Died	Male	26-45		Passive	No	No	No	No	Yes	No	No	Positive	no	no		neg	no
Transfer out	Male	26-45	urban	Passive	No	No	No	No	Yes	No	No	Negative	yes	hiv_neg		neg	no
Completed	Male	26-45		Passive	Yes	No	No	No	Yes	No	No	Negative	yes	hiv_neg		pos	yes
On treatment	Male	26-45	rural	Passive	No	No	No	No	Yes	No	No	Negative	yes	hiv_neg		neg	yes
Completed	Female	26-45	urban	Active	No	No	No	No	No	No	No		no			pos	no
Cured	Male	26-45	urban	Passive	No	No	No	No	Yes	No	No	Negative	yes	hiv_neg		pos	no
Completed	Female	26-45	rural	Passive	No	No	No	No	Yes	No	No	Negative	yes	hiv_neg		neg	no
This is a portion of the data; to view all the data, please download the file.

Dataset 1.Data for patients analyzed in the retrospective cohort study.

Discussion

We found that only 64% of patients treated for drug-sensitive TB in Kyiv Oblast achieved treatment cure or completion, and this is far below global treatment success rates of 83%¹. We also identified alcohol abuse and HIV as patient determinants of failure, death or default in this setting. Our findings support the idea that TB control efforts in this setting should urgently prioritize interventions aimed at the patient populations identified as at risk.

We show that routinely collected baseline programmatic data in Ukraine’s NTP reasonably predicts patients at high risk of poor DSTB treatment outcome at the beginning of treatment. Notably, this routine program data did not include other known predictors of poor TB treatment outcomes (e.g. DM, smoking, socioeconomic status, and poor nutritional status)^{4,9,10,14–17}, therefore, we could not evaluate relative contributions of these unmeasured patient factors. Furthermore, the UNTP does not employ validated screening tools for harmful alcohol or substance use but instead relies on patient self-report; stigma associated with alcohol abuse and IVDU likely limits patients’ willingness to accurately report this information. Hence, rates of reported alcohol and IVDU were likely underestimated. Studies from other settings have demonstrated that incorporating dedicated treatment for alcohol abuse within TB programs is feasible¹⁸ and access to treatment for substance use improves TB outcomes^19,20. Nevertheless, despite the limitations of routine program data, our findings demonstrate that within the current operations of Ukraine’s TB program, there is sufficient data to identify patients who can be targeted for early intervention to mitigate their risk of poor outcome. Improved screening for additional co-morbidities will also help identify other populations at higher risk for poor TB outcomes in this setting.

It is also important to note that health system factors influence patient-predictors and limit treatment success rates among patients with and without known risk factors at baseline. Hence, TB control efforts in this setting should also address how the current TB care delivery system in Ukraine adversely affects treatment outcomes for all patients. For instance, while the TB program in Kyiv Oblast tested most patients for HIV, less than half of HIV/TB co-infected patients were initiated on ART. We do not have data on the specific reasons why many HIV-positive patients were not initiated on ART during TB treatment. Anecdotal reports indicate TB providers sometimes defer ART for patients with high CD4 counts despite national guidelines for ART initiation regardless of CD4 count. Even among those treated, ART did not significantly mitigate the risk of poor TB treatment outcomes. Timing of ART initiation also did not predict outcome. Health system factors such as quality of ART and inconsistent availability may explain these findings. Provision of ART to all HIV/TB patients, as recommended by the WHO²¹, will likely improve treatment success rates among co-infected patients. However, additional system interventions such as integrated HIV and TB care during the entire phase of TB treatment may also be required to sufficiently address the excess risk of poor TB outcomes among HIV patients in this setting.

Previous evaluations of Ukraine’s TB program have already enumerated specific health system factors that hamper successful treatment outcomes, including: unnecessarily prolonged hospital-based care; interruptions in drug supply; protocol deviations; limited social support for patients; and suboptimal infection prevention that increases nosocomial TB transmission^22,23. Our findings have been presented to policy makers in Ukraine including during a National Round Table discussion in Kyiv (November 2015) in preparation for updates to UNTP guidelines, which will focus on scaling up ambulatory-based care, targeted interventions for populations at risk of poor outcomes and patient-oriented approaches to improve treatment adherence. New policy changes create the possibility of further analyzing health system contributions to poor outcomes, and assessing how systems improvements will influence success rates among patients with baseline increased risk of poor outcomes. Future research can also evaluate providers’ understanding of and compliance with guidelines.

Conclusion

We found extremely low rates of treatment cure and completion for new drug sensitive TB in the Kyiv Oblast of Ukraine. In addition to specific interventions targeted at vulnerable patients, there is also a need to address and mitigate the impact of health system factors on Ukraine’s TB treatment success rates.

Data availability

Data have been de-identified for ethical, data protection and security reasons. Permission for use and publication of the anonymized data granted by the Institutional Review Board of Bogomolets Medical University.

Dataset 1. Data for patients analyzed in the retrospective cohort study. DOI, 10.5256/f1000research.12687.d179513²⁴.

Competing interests

No competing interests were disclosed.

Grant information

Funding support to OA was provided by the National Institute on Drug Abuse training grant T32 DA013911 and the NIH-NIMH grant R25MH83620.

The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Faculty Opinions recommended

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