Approaches to developing de novo cancer population models to examine questions about cancer and race in bladder, gastric, and endometrial cancer and multiple myeloma: the Cancer Intervention and Surveillance Modeling Network incubator program.

BACKGROUND: We are developing 10 de novo population-level mathematical models in 4 malignancies (multiple myeloma and bladder, gastric, and uterine cancers). Each of these sites has documented disparities in outcome that are believed to be downstream effects of systemic racism. METHODS: Ten models are being independently developed as part of the Cancer Intervention and Surveillance Modeling Network incubator program. These models simulate trends in cancer incidence, early diagnosis, treatment, and mortality for the general population and are stratified by racial subgroup. Model inputs are based on large population datasets, clinical trials, and observational studies. Some core parameters are shared, and other parameters are model specific. All models are microsimulation models that use self-reported race to stratify model inputs. They can simulate the distribution of relevant risk factors (eg, smoking, obesity) and insurance status (for multiple myeloma and uterine cancer) in US birth cohorts and population. DISCUSSION: The models aim to refine approaches in prevention, detection, and management of 4 cancers given uncertainties and constraints. They will help explore whether the observed racial disparities are explainable by inequities, assess the effects of existing and potential cancer prevention and control policies on health equity and disparities, and identify policies that balance efficiency and fairness in decreasing cancer mortality.

An acceptance-based, intersectional stigma coping intervention for people with HIV who inject drugs-a randomized clinical trial.

Background: People with HIV who inject drugs experience intersecting forms of stigma that adversely impact care access. This RCT aimed to evaluate effects of a behavioral intersectional stigma coping intervention on stigma and care utilization. Methods: We recruited 100 participants with HIV and past-30-day injection drug use at a non-governmental harm reduction organization in St. Petersburg, Russia, and randomized them 1:2 to receive usual services only or an additional intervention of three weekly 2-h group sessions. Primary outcomes were change in HIV and substance use stigma scores at one month after randomization. Secondary outcomes were initiation of antiretroviral treatment (ART), substance use care utilization, and changes in frequency of past-30-days drug injection at six months. The trial was registered as NCT03695393 at clinicaltrials.gov. Findings: Participant median age was 38.1 years, 49% were female. Comparing 67 intervention and 33 control group participants recruited October 2019-September 2020, the adjusted mean difference (AMD) in change in HIV and substance use stigma scores one month after baseline were 0.40, (95% CI: -0.14 to 0.93, p = 0.14) and -2.18 (95% CI: -4.87 to 0.52, p = 0.11), respectively. More intervention participants than control participants initiated ART (n = 13, 20% vs n = 1, 3%, proportion difference 0.17, 95% CI: 0.05-0.29, p = 0.01) and utilized substance use care (n = 15, 23% vs n = 2, 6%, proportion difference 0.17, 95% CI: 0.03-0.31, p = 0.02). The adjusted median difference in change in injecting drug use frequency 6 months after baseline was -3.33, 95% CI: -8.51 to 1.84, p = 0.21). Five not intervention-related serious adverse events (7.5%) occurred in the intervention group, one (3.0%) serious adverse event in the control group. Interpretation: This brief stigma-coping intervention did not change stigma manifestations or drug use behaviors in people with HIV and injection drug use. However, it seemed to reduce stigma's impact as an HIV and substance use care barrier. Funding: R00DA041245, K99DA041245, P30AI042853.

The impacts of COVID-19 on structural inequities faced by people living with HIV who inject drugs: A qualitative study in St. Petersburg, Russia.

BACKGROUND: People who inject drugs (PWID) living with HIV may be disproportionately impacted by pandemic restrictions. This study qualitatively explored the impacts of the SARS-CoV-2 pandemic on PWID with HIV in St. Petersburg, Russia. METHODS: In March and April 2021, we conducted remote, semi-structured interviews with PWID with HIV, health care providers, and harm reductionists. RESULTS: We interviewed 25 PWID with HIV (aged 28-56 years, 46% female) and 11 providers. The pandemic exacerbated economic and psychological challenges experienced by PWID with HIV. Simultaneously, barriers to HIV care access, ART prescription refill and dispensing and police violence, which hindered the health and safety of PWID with HIV, were themselves hindered from normal operations by the pandemic, significantly reducing these burdens. CONCLUSION: Pandemic responses should account for the unique vulnerabilities of PWID with HIV to avoid worsening the structural violence they already experience. Wherever the pandemic decreased structural barriers, such as institutional, administrative, and bureaucratic challenges and state violence enacted by police and other elements of the criminal justice system, such changes should be protected.

HIV, substance use, and intersectional stigma: Associations with mental health among persons living with HIV who inject drugs in Russia.

HIV stigma is associated with negative physical and mental health outcomes. Intersectional stigma among persons living with HIV (PLHIV) results from interrelated, synergistic impacts of experiencing multiple stigma forms. Its relation with mental health outcomes is still an emerging area of study in this key population. This study aimed to evaluate associations of intersectional stigma, defined as endorsing high levels of HIV and substance use stigmas, with depressive and anxiety symptoms in a cohort of 111 PLHIV who inject drugs in St. Petersburg, Russia. Over a third of participants (37%) reported experiencing intersectional stigma (i.e., both stigma scores above the median). In adjusted analysis, lower Patient Health Questionnaire depression scale (PHQ-9) scores (beta (ß=-4.31, 95% CI: -7.11 - -1.51, p = 0.003) and Generalized Anxiety Disorders Scale (GAD-7) scores (ß=-3.64, 95% CI: -5.57 - -1.71, p < 0.001) were associated with having low scores for both HIV and substance use stigmas. Lower PHQ-9 scores (ß=-3.46, 95% CI: -5.72 - -1.19, p = 0.003) and GAD-7 scores (ß=-3.06, 95% CI: -4.62 - -1.50, p < 0.001) were also associated with high stigma on either HIV or substance use stigma scales. Controlling for demographics, depressive symptoms approximately linearly increased from both forms of stigma low to experiencing either form of stigma high to experiencing intersectional stigma, while levels of anxiety symptoms were comparable among participants with both types of stigma low and one stigma high. Participants who experienced intersectional stigma reported the greatest severity of both depressive and anxiety symptoms, as compared to individuals who endorsed low stigma scores (i.e., low stigma on both HIV and substance use stigma scales) or high scores of only one form of stigma. This suggests that intersectional stigma in this population of PLHIV who inject drugs in Russia is linked with worsened mental health outcomes, exceeding the effects of experiencing one form of stigma alone. Interventions to help people cope with intersectional stigma need to consider affective symptoms and tailor coping strategies to address impacts of multiple forms of mental health distress.

Tuberculosis Co-Infection Is Common in Patients Requiring Hospitalization for COVID-19 in Belarus: Mixed-Methods Study.

A significant drop in tuberculosis (TB) case-finding has been widely reported during the period of the COVID-19 pandemic. To address a decrease in TB notification, Belarus introduced laboratory TB testing in patients with the laboratory-confirmed coronavirus disease 2019 (COVID-19). We conducted a secondary analysis of health records among 844 patients with laboratory-confirmed COVID-19 diagnosis who were admitted to repurposed departments at TB hospitals and who were tested by Xpert MTB/RIF (Cepheid Inc., Sunnyvale, CA, USA) in five Belarus regions between April and October 2021. Quantitative analysis followed by 13 individual interviews with health managers, physicians, and nurses participating in the intervention. Most patients were male (64%) and mean age was 43.5 ± 16 years. One in twenty (n = 47, 5.6%) patients were co-infected with active pulmonary TB, and over one-third of them (n = 18) had rifampicin resistance. In-hospital mortality was comparable in patients with and without TB co-infection (2.1% and 2.3% respectively, p > 0.99). Laboratory TB testing among patients with COVID-19 at repurposed departments of TB hospitals is feasible in Belarus and may improve TB case-finding.

Police abuse and care engagement of people with HIV who inject drugs in Ukraine.

Police abuse affects people who inject drugs (PWID), including those with HIV, and negatively impacts care engagement. This cross-sectional study evaluated police abuse among PWID receiving MOUD (medication for opioid use disorder) living with HIV and associations with HIV treatment adherence and receipt of NGO services. We assessed lifetime and past six-month rates of police abuse among a cohort of Ukrainian PWID with HIV receiving MOUD (n = 190) from August to September 2017. Logistic regression models evaluated associations between past six-month police abuse and past 30-day antiretroviral therapy (ART) adherence, and past six-month NGO service receipt. Almost all (90%) participants reported lifetime police abuse: 77% reported physical violence and 75% reported paying the police to avoid arrest. One in four females (25%) reported police-perpetrated sexual violence. Recent police abuse was reported by 16% of males and 2% of females and was not associated with ART adherence (aOR: 1.1; 95% CI:0.3-5.0) or NGO service receipt (aOR: 3.4; 95% CI:0.6-18.3). While lifetime police abuse rates were high, few participants reported recent police abuse, which was not linked to care engagement. These trends should encourage the Ukrainian government for public health-public safety partnerships and legal interventions to eliminate human rights violations against PWID living with HIV.

Addressing intersectional stigma as a care barrier for HIV-positive people who inject drugs: Design of an RCT in St. Petersburg, Russia.

BACKGROUND: HIV-positive people who inject drugs (PWID) experience stigma related to their substance use and HIV, with adverse consequences to their health care utilization and mental health. To help affected individuals cope with their intersectional stigma and reduce its negative impact on health and health care, we adapted a behavioral stigma coping intervention for this HIV key population. OBJECTIVE: To conduct a randomized controlled trial (RCT) testing the 'Stigma Coping to Reduce HIV risks and Improve substance use Prevention and Treatment' (SCRIPT) intervention, a community-based, adapted form of Acceptance and Commitment Therapy (ACT), for PWID living with HIV in St. Petersburg, Russia. METHODS: We recruited 100 PWID living with HIV from civil society organizations (CSO) delivering harm reduction and HIV prevention services in St. Petersburg, Russia. We randomized participants 2:1 to receive either the intervention (three adapted ACT sessions in a group format over one month and usual CSO care) or usual CSO care alone. ACT aims to help affected individuals cope with stigma by increasing their psychological flexibility to handle stigma-related negative expectations, emotions and experiences. The primary outcomes were satisfaction with the intervention, and changes in HIV and substance use stigma scores. CONCLUSIONS: Stigma coping interventions targeting HIV-positive PWID outside of formal health care settings may help them confront negativities in their lives originating from intersectional stigma and reduce stigma's impact as a health care barrier.

Short and long-term outcomes of video observed treatment in tuberculosis patients, the Republic of Moldova.

INTRODUCTION: The Republic of Moldova is among the 18 high priority countries for tuberculosis (TB) in Europe. This study compared adherence and short and long-term TB treatment outcomes for TB patients who experienced asynchronous Video Observed Treatment (aVOT) during three months of outpatient treatment versus Directly Observed Treatment (DOT) in operational conditions in 2016-2017 in Chisinau. METHODOLOGY: We used secondary data from the 2016-2017 Randomized Clinical Trial (RCT) that piloted the aVOT Strategy in Chisinau and data from the national TB register. Relative risk was selected as a measure of association in analysis of treatment strategies (aVOT and DOT under operational conditions) and short and long-term treatment outcomes. RESULTS: From 647 TB patients included in the study, 169 followed the treatment strategy in the RCT (83 in aVOT and 86 in DOT) and 478 were on DOT in operational conditions. Those in aVOT were more likely to have favourable short-term outcome than patients with DOT in operational conditions (RR 0.07; p < 0.001). TB recurrence as an indicator for the long-term outcome, was observed in group with DOT in operational conditions (40 cases, p = 0.006). CONCLUSIONS: This study demonstrated that the aVOT treatment strategy was associated with better adherence and both short and long-term TB treatment favourable outcomes. aVOT as a new patient-centred approach supporting TB patients on improving treatment adherence and outcomes might be recommended as an alternative to DOT strategy in the Republic of Moldova.

Does optimized adherence support improve treatment outcomes in RR / MDR-TB patients on 18-20 months regimen in Tbilisi, Georgia?

INTRODUCTION: Adherence to second-line antituberculosis drug is challenging. A combination of strategies needs to be implemented to achieve adherence. In Georgia an optimized adherence support (OAS) - a package of education, psychosocial support and adherence counselling - was added to the already existing package of adherence support (supervised treatment, adherence incentives, transport cost reimbursement) to improve adherence and increase treatment success. We assessed the additive benefits of OAS on adherence and treatment outcomes. METHODOLOGY: This was a before and after cohort study using routine programme data in the National Center for Tuberculosis and Lung Diseases in Tbilisi. All adult rifampicin- and multidrug-resistant tuberculosis (RR/MDR-TB) patients enrolled for treatment under directly observed therapy in the NCTLD during the period before (June 2015 - January 2016) and after (June 2017 - January 2018) were included in the study. Primary outcomes were: i) adequate adherence defined as ≥ 85% of days covered by TB medication during the whole treatment period; ii) final treatment outcomes. RESULTS: Of 221 RR/MDR-TB, most patients were male (76%, N = 167) with a mean age of 41 ± 14 years. Adherence data was available for 111 patients in the 'before' and 97 patients in the 'after' cohort. Adequate adherence was achieved by 62% (69/111) in the 'before' and 70% (68/97) in the 'after' cohort (p = 0.290). Overall treatment success was 64% (73/114) and 63% (67/107) in the 'before' and 'after' cohorts respectively (p = 0.937). CONCLUSIONS: Implementation of OAS had modest effect on adherence and had no additive benefits on treatment outcomes among RR/MDR-TB patients on 18-20 months regimen.

Hospitalizations and Treatment Outcomes in Patients with Urogenital Tuberculosis in Tashkent, Uzbekistan, 2016-2018.

Despite the global shift to ambulatory tuberculosis (TB) care, hospitalizations remain common in Uzbekistan. This study examined the duration and determinants of hospitalizations among adult patients (≥18 years) with urogenital TB (UGTB) treated with first-line anti-TB drugs during 2016-2018 in Tashkent, Uzbekistan. This was a cohort study based on the analysis of health records. Of 142 included patients, 77 (54%) were males, the mean (±standard deviation) age was 40 ± 16 years, and 68 (48%) were laboratory-confirmed. A total of 136 (96%) patients were hospitalized during the intensive phase, and 12 (8%) had hospital admissions during the continuation phase of treatment. The median length of stay (LOS) during treatment was 56 days (Interquartile range: 56-58 days). LOS was associated with history of migration (adjusted incidence rate ratio (aIRR): 0.46, 95% confidence interval (CI): 0.32-0.69, p < 0.001); UGTB-related surgery (aIRR: 1.18, 95% CI: 1.01-1.38, p = 0.045); and hepatitis B comorbidity (aIRR: 3.18, 95% CI: 1.98-5.39, p < 0.001). The treatment success was 94% and it was not associated with the LOS. Hospitalization was almost universal among patients with UGTB in Uzbekistan. Future research should focus on finding out what proportion of hospitalizations were not clinically justified and could have been avoided.

Effectiveness and safety of delamanid- or bedaquiline-containing regimens among children and adolescents with multidrug resistant or extensively drug resistant tuberculosis: A nationwide study from Belarus, 2015-19.

There is limited evidence describing the safety and effectiveness of bedaquiline and delamanid containing regimens in children and adolescents with Multidrug-Resistant Tuberculosis (MDR-TB) and Extensively Drug-Resistant Tuberculosis (XDR-TB) globally. In this nationwide descriptive cohort study from Belarus, we examined adverse drug events, time to culture conversion, treatment outcomes including post-treatment recurrence among children and adolescents (<18 years of age) treated with bedaquiline and/or delamanid containing regimens from 2015 to 2019. Of the 40 participants included (55% females; age range 10-17 years), 20 (50%) had XDR-TB and 15 (38%) had resistance to either fluoroquinolone or second-line injectable. Half of the patients received delamanid and another half received bedaquiline with one patient receiving both drugs. AEs were reported in all the patients. A total of 224 AEs were reported, most of which (76%) were mild in nature. Only 10 (5%) AEs were graded severe and one AE was graded life-threatening. A total of 7 AEs (3%) were classified as 'serious' and only one patient required permanent discontinuation of the suspected drug (linezolid). Most of the AEs (94%) were resolved before the end of treatment. All patients culture-positive at baseline (n=34) became culture-negative within three months of treatment. Median time to culture conversion was 1.1 months (interquartile range: 0.9-1.6). Two patients were still receiving treatment at the time of analysis. The remaining 38 patients successfully completed treatment. Among those eligible and assessed at 6 (n=32) and 12 months (n=27) post-treatment, no recurrences were detected. In conclusion, treatment of children and adolescents with MDR-TB and XDR-TB using bedaquiline and/or delamanid containing regimens was effective and had favourable safety profile. Achieving such excellent outcomes under programmatic settings is encouraging for other national tuberculosis programmes, which are in the process of introducing or scaling-up the use of these new drugs in their countries.

Effectiveness and cardiovascular safety of delamanid-containing regimens in adults with multidrug-resistant or extensively drug-resistant tuberculosis: A nationwide cohort study from Belarus, 2016-18.

To address the sub-optimal treatment outcomes among patients with multidrug-resistant (MDR-TB) and extensively drug-resistant tuberculosis (XDR-TB), the National TB Programme in Belarus started using new drugs such as bedaquiline and delamanid in 2015-16. In this study, we assessed cardiovascular safety and effectiveness (culture conversion, treatment outcomes and post-treatment recurrence) of delamanid-containing regimens among adults (>18 years) with MDR-TB or XDR-TB from June 2016 to February 2018. This was a nationwide cohort study involving analysis of routinely collected programme data from the national and six regional TB hospitals. Cardiovascular adverse events (AEs) were classified as serious or not, based on international guidelines. We conducted Cox proportional hazards regression and calculated adjusted hazards ratio(aHR) and 95% confidence intervals(CI) to evaluate factors associated with AEs and unsuccessful treatment outcomes (death, failure and lost-to-follow-up). Of 125 patients enrolled (35, 28% females; mean age 43 years), 85(68%) had XDR-TB. All the patients received delamanid and 20 patients received both delamanid and bedaquiline. Cardiovascular AEs (177 episodes in total), were observed in the majority (73%) of patients but were mild and managed easily. The most common cardiovascular AEs were QTcF prolongation (64/177, 36%) and other electrocardiography (ECG) abnormalities (40/177, 23%). There were two instances of serious AEs leading to death, both of which were not related to delamanid. In multivariable analysis, male sex (aHR 0.72; 95% CI 0.51-0.99), and baseline ECG abnormalities (aHR 1.68; 95% CI 1.19-2.36) were associated with cardiovascular AEs. Median time to culture conversion was 1.1 months (interquartile range: 1.0-2.1). Culture conversion was observed in 115 (92%) patients at six months of treatment and 110 (88%) completed the treatment successfully. Loss to follow-up, failure and death were observed in 6%, 4% and 2% patients respectively. Among those assessed at 12 months post-treatment (n=33), recurrence was seen in one patient. The only factor associated with unsuccessful treatment outcomes in multivariable analysis was baseline Hepatitis C co-infection (aHR 3.61; 95% CI 1.09-11.95). In conclusion, treatment using delamanid-containing regimens was effective and had a favourable safety profile. We hope our findings inform the development of national clinical guidelines and scale-up of new drugs in other countries.

Do catastrophic costs impact treatment outcomes in people with rifampicin-resistant tuberculosis in the Republic of Moldova?

The Republic of Moldova is among the 30 Rifampicin-Resistant and/or Multidrug-Resistant (RR/MDR) Tuberculosis (TB) high burden countries in the world. Despite free TB diagnostics and treatment, TB patients face substantial economic losses and this may impact overall treatment outcomes. We assessed if there is an association between TB-related catastrophic costs and TB treatment outcomes. We conducted a cohort study using data from patient records and a survey that quantified catastrophic costs among RR/MDR-TB affected households in the Republic of Moldova in 2016. We included adult patients (age ≥18 years) with RR/MDR-TB who had been in inpatient (intensive phase) or outpatient (continuous phase) treatment for at least 2 months. Unfavourable treatment outcome, such as failure, death or lost to follow-up, was the primary outcome variable. The definition of catastrophic TB-related costs followed the World Health Organisation (WHO) guidelines: costs due to TB ≥20% of annual household income. Log-binomial regression was used to assess association between the outcome and catastrophic TB-related costs adjusting for other socio-demographic, behavioural and clinical covariates.  In total 287 RR/MDR-TB patients (78% males, mean age 42 years) were included. Of them, 30% experienced catastrophic TB-related costs. Overall, one in five patients (21%) had unfavourable treatment outcome, such as treatment failure (5%), death (8%) or lost to follow-up (8%). The experience of catastrophic TB-related costs was not associated with unfavourable treatment outcome [adjusted relative risk (aRR)=0.88, 95% CI: 0.50-1.50]. Major factors independently associated with unfavourable TB treatment outcomes were poverty (aRR=2.07; 95% CI: 1.06-4.07), urban residence (aRR=1.99; 95% CI: 1.12-3.52) and positive HIV (Human Immunodeficiency Virus) status (aRR=2.61; 95% CI: 1.31-4.89). As a result, we failed to find an association between catastrophic costs and treatment outcomes of RR/MDR-TB patients in the Republic of Moldova. However, we found that patients from poor households and urban areas were twice more likely to achieve unfavourable TB treatment outcomes disregarding whether they experienced catastrophic costs or not. Also, TB/HIV patients and urban residents were identified as the most vulnerable groups with higher risk of unfavourable treatment outcome and TB-related costs.

Incidence rate and time to serious adverse events among rifampicin resistant tuberculosis patients in Georgia treated with new and repurposed anti-tuberculosis drugs, 2016-2018.

Considering the complexity of second-line anti-tuberculosis (TB) treatment regimens, the management of drug-resistant TB (DR-TB) in Georgia remains a major challenge. Since the introduction of new and repurposed anti-TB medications, the implementation of active TB Drug Safety Monitoring (aDSM) was a critical program component to help establish safety and manage all treatment related Serious Adverse Events (SAEs). In our study, we aimed to describe the occurrence, characteristics and timing of SAE among patients with Rifampicin Resistant and Multi-Drug Resistant TB (RR/MDR-TB) receiving new and/or repurposed anti-TB medications (bedaquiline, delamanid, linezolid, clofazimine, imipenem) during the period of 2016-2018 in Georgia and identify predictors of SAE. The data were obtained from the medical charts, electronic database and standardized aDSM reports During 2016-2018 period in total 970 people with RR/MDR-TB were notified in Georgia and 388 of them received new and/or repurposed TB drugs as part of their treatment regimen and all were included into the study. The results showed a total of 73 SAEs registered among 49 (12.6%) patients receiving new and/or repurposed drugs. The overall SAE incidence rate per 100 person-months was 1.16. The severity of the majority of the SAEs (46.6%) was grade III and 21.9% were grade IV. The most common SAE reported was hepatotoxicity, with an incidence of 0.26 per 100 person-month (n=16, 21.9%) followed by cardiotoxicity with an incidence of 0.16 per 100 person-month (n=10, 13.7%). Median time to SAE occurrence was 183 days (IQR 84 - 334) after treatment initiation. Resistance profile was the only predictor associated with occurrence of a SAEs. There was increased hazard of SAEs among patients with XDR-TB (adjusted HR=2.18, 95% CI: 1.12-4.23). Our findings on SAEs among patients treated with new or repurposed anti-TB drugs are echoing the findings available in the literature. They highlight the need for close monitoring of patients and underlines the importance of the aDSM during the whole treatment. Safety profile of the medications and combinations used are yet to be established and larger datasets comprised of patients receiving same treatment regimens need to be utilized.

Factors associated with time to sputum culture conversion of rifampicin-resistant tuberculosis patients in Klaipeda, Lithuania in 2016-2019: a cohort study.

The global proportion of successful treatment outcomes of Multidrug-Resistant/Rifampicin-Resistant Tuberculosis (MDR/RR-TB) remains unacceptably low. Time to culture conversion is important in making treatment-related decisions and is used as an interim predictor of pulmonary MDR/RR-TB treatment success. No previous studies have been conducted to assess determinants of time to culture conversion for MDR/RR-TB patients in Lithuania. Secondary analysis of data of culture-positive MDR/RR-TB patients, treated in Republican Klaipeda Hospital between 1st July 2016 and 1st July 2019 was performed. Culture conversion was defined as two consecutive negative cultures on solid media submitted at least 30 days apart. Factors associated with culture conversion were estimated by crude and multivariable Cox regression accounting for competing risks. In total, 115 consecutive patients starting treatment were included in the study. Of them, the majority was male (86/115; 74.8%) with a mean age of 48 (standard deviation (SD) ±12) years and Human Immunodeficiency Virus (HIV) negative (105/115; 91.3%). Nearly two-thirds (72/115; 62.6%) had XDR (extensive drug resistance) or MDR/RR-TB with additional resistance to second-line injectables or fluoroquinolones. Of 115 culture-positive patients at baseline, 103 (89.6%) patients achieved culture conversion during 12 months of treatment. The median time to culture conversion was 1.1 months (interquartile range: 0.9-1.8). Patients aged ≥60 years compared with <40 years [adjusted hazard ration (aHR): 0.40, 95% confidence interval (CI): 0.18-0.86], smokers (aHR: 0.39, 95% CI: 0.2-0.73), patients with positive sputum smear microscopy at baseline (aHR: 0.40, 95% CI: 0.25-0.63), cavities on initial chest X-ray (aHR: 0.56, 95% CI: 0.35-0.88) and resistance to at least one fluoroquinolone drug (aHR: 0.52, 95% CI: 0.32-0.84) were slower to culture convert. In conclusion, we recommend providing additional counseling, treatment adherence interventions and scale up the use of new and repurposed TB drugs to patient groups at risk of worse interim treatment outcome: patients aged 60 and above, with resistance to fluoroquinolones, smear-positive, smokers, or with signs of extensive disease evident on initial chest radiography.

Factors associated with culture conversion among adults treated for pulmonary extensively drug-resistant tuberculosis during 2018-2019 in the Russian Federation: an observational cohort study.

Treatment outcomes for Multidrug/Rifampicin-Resistant Tuberculosis (MDR/RR-TB) and Extensively Drug-Resistant Tuberculosis (XDR-TB) remain poor across the globe and in the Russian Federation. Treatment of XDR-TB is challenging for programmes and patients often resulting in low success rates and onward transmission of drug-resistant strains. Analysis of factors affecting culture conversion rate among XDR-TB patients may serve as a basis for optimization of treatment regimens. We conducted a retrospective cohort study using health records from 54 patients with pulmonary XDR-TB treated at a tertiary level facility in the Russian Federation. The study population included adult patients with culture-positive pulmonary XDR-TB who started treatment between 1 January 2018-30 June 2019. Culture conversion was defined as two consecutive negative cultures, collected at least 30 days apart. The date of sputum culture conversion was taken from the first of two consecutive negative sputum cultures fulfilling these criteria. We measured time to culture conversion using cumulative incidence functions accounting for competing risks and applied binary cause-specific Cox regressions to assess associated factors. Sputum culture conversion was recorded for 43 (79.6%) patients. Median time to culture conversion adjusted for competing risk of loss to follow up was 4 months [95% confidence interval (CI): 2-5]. The number of patients who had culture converted by treatment months 2, 4, and 6 were 12 (22%), 29 (54%) and 38 (70%) respectively. In unadjusted analysis, positive baseline sputum smear microscopy [hazard ratio (HR): 0.34, 95% CI: 0.18-0.66; p=0.001), hepatitis C (HR: 0.35, 95% CI: 0.14-0.89; p=0.023], and human immunodeficiency virus (HR: 0.30 95%, CI: 0.09-0.97; p=0.045), and receipt of fewer than 4 effective drugs in the treatment regimen (HR: 0.13, 95% CI: 0.03-0.60; p=0.009) were associated with delayed culture conversion. When compared to their combined use, patients receiving regimens with bedaquiline only (HR: 0.12, 95% CI: 0.03-0.49; p=0.003) or linezolid only (HR: 0.21, 95% CI: 0.06-0.69; p=0.010) were less likely to achieve timely culture conversion. Factors delaying sputum culture conversion should be considered in the management of patients with XDR-TB and considered by clinicians for regimen design and treatment strategies. Our study outlines the importance of simultaneous inclusion of bedaquiline and linezolid in treatment regimens for patients with XDR-TB to reduce time to sputum conversion and increase treatment success.

Effectiveness and safety of fully oral modified shorter treatment regimen for multidrug-resistant tuberculosis in Georgia, 2019-2020.

Tuberculosis treatment is challenging, especially among people with drug-resistant forms of tuberculosis. The introduction of fully oral modified short treatment regimen has a great potential to shorten duration of treatment, improve safety and ultimately increase treatment success rate. In 2019 Georgia has piloted the modified fully oral shorter treatment regimen in a routine programmatic condition. Our study aimed to evaluate effectiveness and safety of the modified shorter treatment regimen in Georgia among the first 25 consecutively enrolled patients with rifampicin-resistant tuberculosis with proven sensitivity to fluoroquinolone and without prior exposure to second-line tuberculosis drugs. Regimen consisted of 9-month daily administration of bedaquilline, linezolid, levofloxacin, clofazimine and cycloserine. Study patients were enrolled between March-August 2019. We used a national electronic surveillance system, medical records and active TB drug-safety monitoring and management database to extract study related data. The mean age of the study participants was 48 years, 68% were male, 8% were HIV positive, 16% had diabetes and 12% tested positive for hepatitis C infection. The median time to culture conversion among 16 patients who were culture positive at treatment initiation was 1.0 (95% CI: 1.0-2.0) month. Of those, by the end of treatment 15 patients converted to negative. Out of the 25 patients in the study cohort 22 (88%) had successful treatment outcome, one patient (4%) died and two (8%) were lost to follow up. The regimen was largely well tolerated. Three patients (12%) experienced serious adverse events, of which in two cases were possibly related to TB drugs in the regimen. Seven patients developed adverse events of interest in eight instances, including musculoskeletal (twice), psychiatric, gastrointestinal disorders, hepatotoxicity, peripheral neuropathy, cardiotoxicity and myelosuppression (once each). In four patients (16%) the duration of the treatment was extended beyond nine months due to insufficient radiological improvements. Our findings demonstrate that good treatment outcomes are achievable in people with fluoroquinolone-sensitive tuberculosis within routine programmatic conditions using fully oral modified short treatment regimen. The extensive use of fully oral modified shorter treatment regimen in Georgia and other high priority countries in the World Health Organization European Region is warranted.

Factors associated with loss to follow-up among people with tuberculosis in the country of Georgia: a cohort study.

Despite having universal access to tuberculosis (TB) treatment, loss to follow-up (LFU) rates remain high in Georgia, 6% among drug-susceptible TB (DS-TB) patients (2017 cohort) and 19% among drug-resistant TB (DR-TB) patients diagnosed in 2016. A cohort study was conducted to analyze secondary data from the Georgian National Tuberculosis Surveillance Database. Study population included adult (≥18 y.o.) patients with bacteriologically confirmed pulmonary TB who were enrolled in Georgian National TB program during 2015-2017. The outcome of interest was loss to follow-up, defined as treatment interruption for more than 2 consecutive months. Patients were stratified by treatment profile (first-line drugs or second-line drugs) and survival analysis was performed within the stratified groups.  A total of 7860 treatment episodes were identified during 2015-2017 which corresponded to 6696 bacteriologically confirmed pulmonary TB treatment episodes of whom 795 (12%) were LFU. After adjustment, final multivariate analysis showed that male sex (aHR 1.5, 95%CI 1.2-2.0), being diagnosed in Tbilisi (aHR 1.3, 95%CI 1.1-1.6), unemployment at the time of diagnosis (aHR 1.7, 95%Ci 1.2-2.3) and previous history of TB treatment were independent risk factors for  LFU (aHR 2.3, 95%CI 1.9-2.8) among patients on first-line drugs. Among patients on second-line drugs being male (aHR 2.0, 95%CI 1.2-3.2), past TB treatment with second-line drugs (aHR 2.2, 95%CI 1.5-3.2) were significantly associated with LFU. LFU rate was high among patients on first-line drugs and second line drugs (10% and 22% respectively). Patients with past TB treatment history should further research to identify factors that lead to treatment interruption in this group. Other factors associated with LFU (being internally displaced person (IDP), being unemployed, and having imprisonment history) were in some level indication of a poor social-economic status, and strengthening approaches for TB care based on patients' need could be considered in light of this finding.

Violence, HIV Risks, and Polysubstance Use Among HIV-Positive People Who Inject Drugs in Ukraine.

Violence experience has been consistently associated with HIV risks and substance use behaviors. Although many studies have focused on intimate partner violence (IPV), the role of violence at a structural level (i.e., police abuse) remains relevant for people who inject drugs. This study evaluated the association of IPV and police-perpetrated violence experiences with HIV risk behaviors and substance use in a cohort of HIV-positive people who inject drugs in Ukraine. We also evaluated possible moderation effects of gender and socioeconomic status in the links between violence exposure and HIV risk and polysubstance use behaviors. Data came from the Providence/Boston-CFAR-Ukraine Study involving 191 HIV-positive people who inject drugs conducted at seven addiction treatment facilities in Ukraine. Results from logistic regressions suggest that people who inject drugs and experienced IPV had higher odds of polysubstance use than those who did not experience IPV. Verbal violence and sexual violence perpetrated by police were associated with increased odds of inconsistent condom use. The odds of engaging in polysubstance use were lower for women in relation to police physical abuse. We found no evidence supporting socioeconomic status moderations. Violence experiences were associated with substance use and sexual HIV risk behaviors in this cohort of HIV-positive people who inject drugs in Ukraine. Trauma-informed prevention approaches that consider both individual and structural violence could improve this population's HIV risks.

RESUMEN: La experiencia de violencia se ha asociado sistemáticamente con las conductas de riesgo para la adquisición o transmisión del VIH y con el uso de sustancias. Aunque muchos estudios se han centrado en la violencia infligida por la pareja íntima (VPI), el papel de la violencia estructural (es decir, el abuso policial) sigue siendo relevante para las personas que se inyectan drogas. Este estudio evaluó la asociación entre las experiencias de violencia perpetrada por la policía y la pareja íntima con los conductas de riesgo para la adquisición o transmisión del VIH y el uso de sustancias en una cohorte de personas VIH positivas que se inyectan drogas en Ucrania. También evaluamos los posibles efectos de moderación del género y el estatus socioeconómico entre la exposición a la violencia y los comportamientos de riesgo para la transmisión del VIH y uso de múltiples sustancias. Los datos provienen del estudio Providence / Boston-CFAR-Ucrania en el que participaron 191 personas infectadas por el VIH que se inyectan drogas, realizado en siete centros de tratamiento de adicciones en Ucrania. Los resultados de las regresiones logísticas sugieren que, en comparación con las personas que se inyectan drogas que no experimentaron IPV, las que experimentaron IPV tenían mayor probabilidad de uso de múltiples sustancias. La violencia sexual perpetrada por la policía se asoció con mayores probabilidades de un uso inconsistente del condón. No encontramos evidencia que apoye las moderaciones de género o estatus socioeconómico. Las experiencias de violencia se asociaron con el uso de sustancias y las conductas sexuales de riesgo para la transmisión del VIH en esta cohorte de personas VIH positivas que se inyectan drogas en Ucrania. Los enfoques de prevención basados en las experiencias traumáticas que tienen en cuenta tanto la violencia individual como la estructural podrían mejorar las conductas de riesgo para la transmission del VIH de esta población.