Modes of HIV transmission among young women and their sexual partners in Ukraine.

BACKGROUND: Ukraine has the second-largest HIV epidemic in Europe, with most new cases officially attributed to heterosexual transmission. Indirect evidence suggested substantial HIV transmission from people who inject drugs (PWID) to their sexual partners. This study examined the extent of heterosexual HIV transmission between PWID and non-drug-using adolescent girls and young women (AGYW). METHODS: A cross-sectional survey recruited AGYW diagnosed with heterosexually-acquired HIV between 2016 and 2019 in nine regions of Ukraine. AGYW were asked to identify and refer their sexual partners ('Partners'), who subsequently underwent HIV testing, and, if positive, HCV testing. Both AGYW and Partners completed an interview assessing HIV risk behaviors prior to AGYW's HIV diagnosis. RESULTS: In August-December 2020, we enrolled 321 AGYW and 64 Partners. Among the Partners, 42% either self-reported IDU or were HCV-positive, indicating an IDU-related mode of HIV transmission. PWID Partners were more likely to report sexually transmitted infections (STI) and had lower educational levels. Of the 62 women who recruited at least one Partner, 40% had a PWID Partner. Within this subgroup, there was a higher prevalence of STIs (52% vs. 24%) and intimate partner violence (36% vs. 3%). Condom use was less common (52% vs. 38% reporting never use), and frequent alcohol or substance use before sex was higher (48% vs 30%) among AGYW with PWID Partner, although this difference did not reach statistical significance. Notably, 52% of women were aware of their Partners' IDU. CONCLUSION: At least 40% of heterosexual transmission among AGYW in Ukraine can be linked to PWID partners. Intensified, targeted HIV prevention efforts are essential for key and bridge populations (PWID and their sexual partners), addressing the biological and structural determinants of transmission between key and bridge populations, such as IDU- and HIV status disclosure, STIs, IPV, and stigma.

Size estimation of key populations and 'bridge populations' based on the network scale-up method in Ukraine.

INTRODUCTION: Correct estimation of the size of key and bridge populations is crucial for an efficient HIV/AIDS response in resource-limited settings, enabling efficient program planning and resource allocation. The hidden nature of these groups poses challenges to traditional methods, leading to the adoption of innovative approaches like the network scale-up method (NSUM). In this article we present the results of a NSUM study conducted in 2020 in Ukraine, focusing on four key populations and three bridge populations, highlighting challenges and contributions to development of the method. METHODS: From July to September 2020, we conducted a nationally representative survey in Ukraine via computer-assisted telephone interviews, and applied the known population method and summation method to estimate social networks sizes. Results were weighted based on individual sampling probability and adjusted for social respect and visibility factors to address potential limitations. RESULTS: Our study achieved a 20% response rate with 10,000 completed interviews. The social network size, using the known population method, was 213 people, and 125 using the summation method. Adjusting for the social respect and visibility, estimated key populations sizes were 295,857 [248,714-343,001] people who inject drugs, 152,267 [109,960-194,573] men who have sex with men, 78,385 [57,146-99,619] sex workers, and 9,963 [7,352-12,571] transgender people, detailed by age and gender. Bridge populations were estimated at 62,162 [50,445-73,879] sexual partners of people who inject drugs, 284,348 [233,113-335,583] clients of sex workers, and 13,697 [7,370-20,026] female partners of men who have sex with men. CONCLUSIONS: NSUM proves reliable for estimating key populations size with appropriate corrections. It shows promise for further use in Ukraine, considering limited geographic coverage of the integrated bio-behavioral studies to use multiplier-based methods. However, the validity concerns persist for estimating bridge populations size, emphasizing the need for further method refinement and addressing implementation issues, particularly those related to data collection.

Preferences and decisional considerations relating to opioid agonist therapy among Ukrainian people who use drugs: A conjoint analysis survey.

Scaling up opioid agonist therapies (OAT) is the most effective strategy to control combined HIV and opioid epidemics, especially in Eastern Europe and Central Asia (EECA), where HIV incidence and mortality continue to increase. Patient concerns about OAT, however, have undermined scale-up. The objective of this study is to understand Ukrainian opioid use disorder patient preferences about OAT to guide the development of an evidence-informed decision aid for clinical decision-making. We conducted a conjoint-based choice (CBC) survey. Participants were asked to about their preferences relating to 7 attributes of OAT (cost, dosing frequency, concerns about withdrawal symptoms, adverse side effects, improvements in quality of life, precipitation of withdrawal and legislative requirements to be registered as a drug dependent person) and 20 attribute levels for receiving OAT under differing potential treatment constraints. Data were analyzed using Hierarchical Bayesian models. Using respondent-driven sampling and random sampling, we recruited 2,028 people who inject drugs with opioid use disorder. Relative importance (RIS) and partial-worth utility scores (PWUS) were used to assess preferences for attributes and thresholds within each attribute. Cost and dosing frequency were the most important attributes (RIS = 39.2% and RIS = 25.2%, respectively) to potential patients, followed by concerns about withdrawal symptoms (RIS = 10.8%), adverse side effects (RIS = 9.0%), quality-of-life improvement (RIS = 7.5%), precipitation of euphoria (5.2%) and requirement to be registered as a drug- dependent person (RIS = 3.1%). The monthly cost-threshold for willingness-to-pay was 1,900 UAH ($70 USD). In Ukraine, where both governmental and private OAT clinics have emerged and provide markedly different delivery strategies, preferences are mostly driven by out-of-pocket expenses, despite many patients being willing to pay for OAT. Programmatic demands (flexibility and ease of acquiring medications) remain an important consideration while for a minority, clinical concerns about withdrawal symptoms, adverse side effects and OAT impact on life play a smaller role.

Integrated biobehavioral surveillance among people who inject drugs in Ukraine, 2007-2020.

BACKGROUND: Repeated integrated biobehavioral surveys (IBBS) have been implemented among people who inject drugs (PWID) in Ukraine to monitor the trends in key epidemiologic and programmatic indicators. METHODS: The study analyzed seven PWID IBBS rounds from 2007 to 2020 in seven Ukrainian cities. Participants were recruited using respondent-driven sampling, tested for HIV and anti-HCV antibodies, and completed a structured questionnaire. Composite weights (based on individual sampling probability and population size) were applied to generate point estimates and confidence intervals for HIV and HCV prevalence, injection risk behaviors, prevention service coverage, and HIV treatment cascade. Multi-level regression assessed temporal trends in these indicators in 2007-2020. RESULTS: The samples consisted of 1587 participants in 2007, 1905 in 2008/9, 3066 in 2011, 2846 in 2013, 2699 in 2015, 2798 in 2017, and 3651 in the 2020 rounds. HIV prevalence decreased from 27% to 19% overall, and among PWID younger than 25 from 10.5% to 5.5%. Anti-HCV prevalence increased from 50% to 73% overall but decreased from 58% to 27% in the younger subgroup. Past-30-days injection risk behaviors consistently decreased, reaching a minimum of 38% for any risk in 2020. HIV treatment cascade indicators and coverage with opioid agonist treatment substantially improved in the last three rounds. Harm reduction services coverage fluctuated, declining from 52% to 33% in the last three rounds. CONCLUSIONS: This analysis demonstrates the potential of repeated IBBS for monitoring the HIV epidemic and program coverage. We confirmed a sustained decline in overall HIV and HCV transmission, likely driven by reduced risky injection practices among PWID. The impact of harm reduction services requires further study. HIV status awareness and treatment coverage among PWID markedly increased, reaching the national average, possibly indicating the success of case-finding and linkage-to-care interventions. The upcoming IBBS round in Ukraine will also assess the impact of the war on service provision, risk behavior, and HIV transmission among PWID.

Low daily oral PrEP adherence and low validity of self-report in a randomized trial among PWID in Ukraine.

BACKGROUND: The efficacy of daily oral pre-exposure prophylaxis (PrEP) in preventing HIV transmission among people who inject drugs (PWID) was demonstrated over a decade ago. However, only a few studies among PWID have since measured PrEP adherence using laboratory markers. METHODS: In this trial, we randomized recently injecting PWID in Kyiv, Ukraine, to receive daily oral TDF/FTC with or without SMS reminders. Enrollment and PrEP initiation took place at an HIV clinic. Subsequent visits at months 1, 3, and 6 were conducted at a community harm reduction center and included a structured interview, adherence counseling, PrEP dispensing, and dried blood spot collection. PrEP adherence was assessed using standard self-reported measures and TDF/FTC biomarkers. RESULTS: A total of 199 PWID (99 SMS, 100 No-SMS) were enrolled, of whom 24 % were women, with a median age of 37. At month 6, 79.4 % (158/199) of participants were retained, with 84 % (133/158) reporting opioid injection and 20 % (31/158) reporting stimulant injection in the past 30 days. 77 % (122/158) reported taking >95 % of PrEP doses in the past month, and 87 % reported taking the last dose within 2 days. Tenofovir diphosphate was detected in 17 % (28/158) of participants, and emtricitabine triphosphate was detected in 25 % (40/158). Only 3 % (5/158) had metabolite levels indicative of consistent PrEP uptake at 4+ doses per week. There was no association between the SMS intervention and TDF/FTC metabolite detection. CONCLUSION: Adherence to daily oral PrEP among actively injecting PWID, without daily supervision or incentives, was extremely low, despite supportive counseling and SMS reminders. We also observed a high rate of discordance between self-report and classification by a validated biomarker of adherence. Given the scarcity of evidence and emerging data suggesting low oral PrEP adherence among PWID, additional implementation studies with TDF/FTC biomarkers are needed to study whether a sufficient level of adherence to daily PrEP is attainable among PWID, especially as long-acting injectable PrEP offers a promising alternative.

Design, implementation and preliminary results of a type-2 hybrid cluster-randomized trial of integrating screening and treatment for major depressive disorder into specialty clinics providing opioid agonist therapies in Ukraine.

INTRODUCTION: Ukraine has a high prevalence of co-occurring disorders (COD), defined as having both substance use (SUD) and psychiatric disorders. Major depressive disorder (MDD) is the most prevalent psychiatric disorder among people with SUD. People with COD experience poor health outcomes, and international agencies propose integrated COD care. In Ukraine, treatment for SUD is delivered in specialized substance use clinics, without providing any other medical services for comorbidities, including MDD. Here we present the protocol, along the with the preliminary results of the MEDIUM project, including observations over the first 6 months. METHODS: A cluster-randomized type-2 hybrid trial was conducted to integrate MDD treatment into specialty clinics providing opioid agonist therapies (OAT) in Ukraine. Twelve clinics in four regions underwent randomization to control (N = 1) vs experimental arms (N = 2) in each region. Clinicians at experimental sites received tele-education through modified project ECHO using a facilitated screening, evaluation, and treatment algorithm of depression, with or without financial incentives. Service-, patient- and provider-level data were collected for the analysis every 6 months for 24 months. PRELIMINARY RESULTS: For service delivery outcomes, 4421 patients enrolled on OAT across all sites were assessed for MDD for screening (76.7%), evaluation with diagnosis (43.5%) and treatment (30.7%) for MDD; 13.8% continued treatment at least for 6 months. For patient-level outcomes, 1345 patients and 54 providers participated in serial surveys every six months. CONCLUSION: This study will be the first to explore integrated COD care in Ukraine and generate evidence on effective service integration and delivery strategies for people with COD receiving treatment at substance use clinics with broader implications for Eastern Europe and Central Asia region.

Causes and risk factors of death among people who inject drugs in Indonesia, Ukraine and Vietnam: findings from HPTN 074 randomized trial.

INTRODUCTION: The HIV Prevention Trials Network (HPTN) 074 study demonstrated a positive effect of an integrated systems navigation and psychosocial counseling intervention on HIV treatment initiation, viral suppression, medication assisted treatment (MAT) enrollment, and risk of death among people who inject drugs (PWID). In this sub-study, we analyzed the incidence, causes, and predictors of death among HIV-infected and uninfected participants. METHODS: The HPTN 074 randomized clinical trial was conducted in Indonesia, Ukraine, and Vietnam. HIV-infected PWID with unsuppressed viral load (indexes) were recruited together with at least one of their HIV-negative injection partners. Indexes were randomized in a 1:3 ratio to the intervention or standard of care. RESULTS: The trial enrolled 502 index and 806 partner participants. Overall, 13% (66/502) of indexes and 3% (19/806) of partners died during follow-up (crude mortality rates 10.4 [95% CI 8.1-13.3] and 2.1 [1.3-3.3], respectively). These mortality rates were for indexes nearly 30 times and for partners 6 times higher than expected in a population of the same country, age, and gender (standardized mortality ratios 30.7 [23.7-39.0] and 5.8 [3.5-9.1], respectively). HIV-related causes, including a recent CD4 < 200 cells/µL, accounted for 50% of deaths among indexes. Among partners, medical conditions were the most common cause of death (47%). In the multivariable Cox model, the mortality among indexes was associated with sex (male versus female aHR = 4.2 [1.5-17.9]), CD4 count (≥ 200 versus < 200 cells/µL aHR = 0.3 [0.2-0.5]), depression (moderate-to-severe versus no/mild aHR = 2.6 [1.2-5.0]) and study arm (intervention versus control aHR = 0.4 [0.2-0.9]). Among partners, the study arm of the index remained the only significant predictor (intervention versus control aHR = 0.2 [0.0-0.9]) while controlling for the effect of MAT (never versus ever receiving MAT aHR = 2.4 [0.9-7.4]). CONCLUSIONS: The results confirm that both HIV-infected and uninfected PWID remain at a starkly elevated risk of death compared to general population. Mortality related to HIV and other causes can be significantly reduced by scaling-up ART and MAT. Access to these life-saving treatments can be effectively improved by flexible integrated interventions, such as the one developed and tested in HPTN 074.

Treatment of opioid use disorder in Ukraine during the first year of the Russia-Ukraine war: Lessons learned from the crisis.

The Russian invasion of Ukraine in February 2022 caused major disruptions of societal functions, including health care. Patients receiving medications for opioid use disorder (MOUD) depend on receiving daily treatment and face a risk of withdrawal in case of medication supply disruption. MOUD are banned in Russia, making treatment continuation impossible in temporarily occupied areas. In this paper, we review the situation with MOUD delivery in Ukraine during the first year of the Russia-Ukraine war. Legislative changes and mobilization of efforts in the time of crisis ensured treatment continuation for thousands of patients. In areas controlled by Ukraine, most patients were receiving take-home doses for up to 30 days, some experienced temporary dosing reductions. Programs in temporarily occupied regions were shut down likely leading to abrupt withdrawal among many patients. At least 10% of patients have been internally displaced. One year into the war, the number of MOUD patients in governmental clinics of Ukraine increased by 17%, and the data suggest that the coverage of private clinics has also increased. But the risks for program stability remain high as the current medication supply relies on one manufacturing facility. Using lessons learned from the crisis, we provide recommendations for future response to minimize the risks of major adverse outcomes among patients treated for opioid use disorder.

Multiple Infection and Human Immunodeficiency Virus Superinfection Among Persons who Inject Drugs in Indonesia and Ukraine.

BACKGROUND: The HIV Prevention Trials Network (HPTN) 074 study evaluated an integrated human immunodeficiency virus (HIV) treatment and prevention strategy among persons who inject drugs (PWID) in Indonesia, Ukraine, and Vietnam. We previously detected multiple HIV infection in 3 of 7 (43%) of seroconverters with 3-8 HIV strains per person. In this report, we analyzed multiple HIV infection and HIV superinfection (SI) in the HPTN 074 cohort. METHODS: We analyzed samples from 70 participants in Indonesia and Ukraine who had viral load >400 copies/mL at enrollment and the final study visit (median follow-up, 2.5 years). HIV was characterized with Sanger sequencing, next-generation sequencing, and phylogenetic analysis. Additional methods were used to characterize a rare case of triple-variant SI. RESULTS: At enrollment, multiple infection was detected in only 3 of 58 (5.2%) participants with env sequence data. SI was detected in only 1 of 70 participants over 172.3 person-years of follow-up (SI incidence, 0.58/100 person-years [95% confidence interval, .015-3.2]). The SI case involved acquisition of 3 HIV strains with rapid selection of a strain with a single pol region cluster. CONCLUSIONS: These data from a large cohort of PWID suggest that intrahost viral selection and other factors may lead to underestimation of the frequency of multiple HIV infection and SI events.

Comparative Clinical Outcomes With Scale-up of Dolutegravir as First-Line Antiretroviral Therapy in Ukraine.

BACKGROUND: Achievement of the UNAIDS 95-95-95 targets requires ARV regimens that are easy to use, well-tolerated, and cost-effective. Dolutegravir (DTG)-based regimens are efficacious and less costly than other common first-line regimens. This study assessed real-world effectiveness of DTG regimens in treatment-naive people living with HIV in Ukraine. METHODS: We extracted data from the national Medical Information System on all adult patients who initiated antiretroviral therapy (ART) with DTG, lopinavir/ritonavir, or efavirenz (EFV) between October 2017 and June 2018, at 23 large clinics in 12 regions of Ukraine. Viral suppression at 12 ± 3 months and retention at 12 months after treatment initiation were the outcomes of interest. RESULTS: Of total 1057 patients, 721 had a viral load test within the window of interest, and 652 (90%) had viral load of ≤ 200 copies/mL. The proportion with suppression was lower in the EFV group [aOR = 0.4 (95% confidence interval: 0.2 to 0.8)] and not different in the LPV group [aOR = 1.6 (0.5 to 4.9)] compared with the DTG group. A 24-month or longer gap between diagnosis and treatment was associated with lower odds of suppression [aOR = 0.4 (0.2 to 0.8)]. Treatment retention was 90% (957/1057), with no significant difference by regimen group. History of injecting drug use was associated with decreased retention [aOR = 0.5 (0.3 to 0.8)]. CONCLUSIONS: DTG-based regimens were comparable with LPV and more effective than EFV in achieving viral suppression among ART-naive patients in a multisite cohort in Ukraine. Treatment retention was equally high in all 3 groups. This evidence from Ukraine supports the ART Optimization Initiative as a strategy to improve efficiency of the ART program without negatively affecting patient clinical outcomes.

Unified European support framework to sustain the HIV cascade of care for people living with HIV including in displaced populations of war-struck Ukraine.

Ukraine is one of the countries in Europe most affected by HIV. The escalation of open war on the European continent has affected HIV care in Ukraine in an unprecedented way. Treating physicians in Europe have little experience on how to handle HIV-specific care under these circumstances. A framework is urgently needed that both defines and sets out strategies to handle the specific challenges for emergency support for people living with HIV, both those staying in Ukraine and those becoming displaced. The optimal allocation of the few available medical resources, primarily antiretroviral therapy, is necessary to best prevent individual morbidity and achieve population transmission control. Professional HIV networks play a central role to create, optimise, and execute support strategies. Through a rapid literature review we identified the key strategies needed to create a support framework, adapted to Ukraine's HIV epidemiology. We produce a unified support framework aiming to reduce the inevitable impact on Ukraine's HIV care cascade now, and when rebuilding it after the war.

The impact of the COVID-19 pandemic on illicit drug supply, drug-related behaviour of people who use drugs and provision of drug related services in Georgia: results of a mixed methods prospective cohort study.

BACKGROUND: This study examines the effects of COVID-19 related restrictions on the supply of illicit drugs, drug-use behaviour among people who use drugs (PWUD) regularly (at least weekly), and drug-related service provision in Tbilisi, Georgia. METHODOLOGY: In this mixed methods study, a cohort of 50 Georgian PWUD recruited through a snow-ball sampling participated in a bi-weekly online survey in April-September, 2020. They also took part in the qualitative telephone interviews at 12- and 24-week follow-up time points. In addition, four key informants (field experts) were interviewed monthly to assess their perceptions of changes in the illicit drug market and drug service delivery. RESULTS: Mean age in the sample was 36 (range 18-60); 39 (78%) were males. Perceived availability of drugs was reduced during the lockdown, and many PWUD switched to alternative substances when preferred drugs were not available. On average, participants used significantly fewer substances over the course of the study, from 3.5 substances in the preceding 14 days to 2.1 (aOR 0.92; 95% CI 0.90-0.94). Consumption of cannabis products declined significantly (aOR 0.89; 95% CI 0.84-0.95), likewise alcohol (aOR 0.94; 95% CI 0.88-1.0), diverted medicinal methadone (aOR 0.85; 95% CI 0.8-0.9) and diverted medicinal buprenorphine (aOR 0.91; 95% CI 0.84-0.99). PWUD cited fewer contacts with drug dealers, the lack of transportation, and the lack of conventional recreational environment as the main reasons for these changes. When access to sterile injection equipment was limited, PWUD exercised risk-containing injection behaviours, such as buying drugs in pre-filled syringes (aOR 0.88; 95% CI 0.80-0.96). Harm reduction and treatment programs managed to adopt flexible strategies to recover services that were affected during the initial stage of the pandemic. CONCLUSIONS: COVID-19-related restrictive measures mediated specific changes in supply models and drug-use behaviours. While adjusting to the new environment, many PWUD would engage in activities that put them under increased risk of overdose and blood-borne infections. Harm reduction and treatment services need to develop and implement protocols for ensuring uninterrupted service delivery during lockdowns, in anticipation of the similar epidemics or other emergency situations.

Preliminary analysis of self-reported quality health indicators of patients on opioid agonist therapy at specialty and primary care clinics in Ukraine: A randomized control trial.

International agencies recommend integrating addiction treatment into primary care for people who inject drugs (PWID) with opioid use disorder (OUD). Empirical data supporting integration that incorporates comprehensive health outcomes, however, are not known. For this randomized controlled trial in Ukraine, adult PWID with OUD were randomized to receive opioid agonist therapy (OAT) in specialty addiction treatment clinics (SATC) or to primary care clinics (PCCs). For those randomized to PCC, they were subsequently allocated to PCCs where clinicians received pay-for-performance (P4P) incentives (PCC with P4P) or not (PCC without P4P). Participating cities had one of each of the three intervention sites to control for geographic variation. Ongoing tele-education specialty training (OAT, HIV, tuberculosis) was provided to all PCCs. While the primary outcome for the parent trial focuses on patient medical record data, this preliminary analysis focuses on assessment of self-reported achievement of nationally recommended quality health indicators (QHIs) which is summed as a composite QHI score. Secondary outcomes included specialty and primary care QHI subscores. This study occurred from 01/20/2018-11/1/2020 with 818 of 990 randomized participants having complete self-reported data for analysis. Relative to SATC (treatment as usual), the mean composite QHI score was 12.7 (95% CI: 10.1-15.3; p<0.001) percentage points higher at PCCs; similar and significantly higher scores were observed in PCCs compared to SATCs for both primary care (PCC vs SATC: 18.4 [95% CI: 14.8-22.0; p<0.001] and specialty (PCC vs SATC: 5.9 [95% CI: 2.6-9.2; p<0.001] QHI scores. Additionally, the mean composite QHI score was 4.6 (95% CI: 2.0-7.2; p<0.001) points higher in participants with long term (>3 months) experience with OAT compared to participants newly initiating OAT. In summary, PWID with OUD receive greater primary care and specialty healthcare services when receiving OAT at PCCs supported by tele-education relative to treatment as usual provided in SATCs. Clinical trial registration: This trial was registered at clinicaltrials.gov and can be found using the following registration number: NCT04927091.

Patient-Reported Treatment Satisfaction and Quality of Life Among People Living with HIV Following the Introduction of Dolutegravir-Based ART Regimens in Ukraine.

In 2017, the government of Ukraine initiated its ART Optimization Initiative, revising its national antiretroviral therapy (ART) guidelines and embracing Dolutegravir (DTG) as a backbone of first-line ART regimens. A cross-sectional survey of 464 ART patients from 22 large ART clinics was carried out in mid-2019. The survey assessed patient-reported outcomes (PROS) including treatment satisfaction, physical health, mental health, depression, side effects of ART, and adherence. The associations between ART regimen and PROs were assessed using bivariable and multivariable generalized estimating equations (GEE) models. More than half (55.6%) of the patients were satisfied with their current ART regimen. Less than a half (45.3%) considered their physical health as good while only 36.9% rated their mental health as good, 21.3% reported moderate or severe depression, 82.3% reported no side effect in the past 4 weeks, and 44.4% reported not missing ART medication in the past month. In adjusted analysis, patients starting ART with DTG had higher treatment satisfaction compared to people continuing LPV-based regimens (aOR = 0.49, 95% confidence interval: 0.22-0.90). Also in adjusted analyses, unemployment, low income, and history of injection drug use were associated with unfavorable PROs. While the results indicate modestly favorable effects of ART Optimization, there is clearly a need for complementary interventions to improve PROs among disadvantaged ART patients in Ukraine.

Challenges of sexually transmitted infections and sexual health among people who inject drugs.

PURPOSE OF REVIEW: This review provides a summary of recently published research on sexually transmitted infections (STI) and related behaviors among people who inject drugs (PWID), covering three major areas: sexual behavior and its role in STI transmission among PWID, multilevel factors associated with STI risk, and strategies addressing sexual health of PWID. This review is timely given the growing priority of combination prevention approaches and integrated care for PWID. RECENT FINDINGS: Modern research improves the understanding that PWID have an increased risk of STI, which varies by gender, setting, type of substance used, and presence of mental disorders. Major socioeconomic and structural factors, specific and nonspecific to PWID, facilitate inequality and sexual risk behavior. Sexual transmission continues to contribute substantially to the spread of bloodborne infections among PWID, accounting for at least 10% of new HIV cases according to epidemiological modeling. Despite the substantial evidence that behavioral interventions can improve sexual health and reduce sex-related risks among PWID, there is a research-practice gap, reflected in the scarcity of implementation studies published recently. SUMMARY: Integration of sexual health into prevention programs for PWID is essential to curb transmission of STI, including HIV, among PWID and their sexual partners.

Engaging People Who Inject Drugs Living With HIV in Antiretroviral Treatment and Medication for Opioid Use Disorder: Extended Follow-up of HIV Prevention Trials Network (HPTN) 074.

BACKGROUND: People who inject drugs (PWID) living with HIV experience inadequate access to antiretroviral treatment (ART) and medication for opioid use disorders (MOUD). HPTN 074 showed that an integrated intervention increased ART use and viral suppression over 52 weeks. To examine durability of ART, MOUD, and HIV viral suppression, participants could re-enroll for an extended follow-up period, during which standard-of-care (SOC) participants in need of support were offered the intervention. METHODS: Participants were recruited from Ukraine, Indonesia and Vietnam and randomly allocated 3:1 to SOC or intervention. Eligibility criteria included: HIV-positive; active injection drug use; 18-60 years of age; ≥1 HIV-uninfected injection partner; and viral load ≥1,000 copies/mL. Re-enrollment was offered to all available intervention and SOC arm participants, and SOC participants in need of support (off-ART or off-MOUD) were offered the intervention. RESULTS: The intervention continuation group re-enrolled 89 participants, and from week 52 to 104, viral suppression (<40 copies/mL) declined from 41% to 29% (estimated 9.4% decrease per year, 95% CI -17.0%; -1.8%). The in need of support group re-enrolled 94 participants and had increased ART (re-enrollment: 55%, week 26: 69%) and MOUD (re-enrollment: 16%, week 26: 25%) use, and viral suppression (re-enrollment: 40%, week 26: 49%). CONCLUSIONS: Viral suppression declined in year 2 for those who initially received the HPTN 074 intervention and improved maintenance support is warranted. Viral suppression and MOUD increased among in need participants who received intervention during the study extension. Continued efforts are needed for widespread implementation of this scalable, integrated intervention.

Trends, Characteristics and Treatment Outcomes of Patients with Drug-Resistant Tuberculosis in Uzbekistan: 2013-2018.

Uzbekistan has a high burden of drug-resistant tuberculosis (TB). Although conventional treatment for multidrug-resistant TB (MDR-TB) and extensively drug-resistant TB (XDR-TB) has been available since 2013, there has been no systematic documentation about its use and effectiveness. We therefore documented at national level the trends, characteristics, and outcomes of patients with drug-resistant TB enrolled for treatment from 2013-2018 and assessed risk factors for unfavorable treatment outcomes (death, failure, loss to follow-up, treatment continuation, change to XDR-TB regimen) in patients treated in Tashkent city from 2016-2017. This was a cohort study using secondary aggregate and individual patient data. Between 2013 and 2018, MDR-TB numbers were stable between 2347 and 2653 per annum, while XDR-TB numbers increased from 33 to 433 per annum. At national level, treatment success (cured and treatment completed) for MDR-TB decreased annually from 63% to 57%, while treatment success for XDR-TB increased annually from 24% to 57%. On multivariable analysis, risk factors for unfavorable outcomes, death, and loss to follow-up in drug-resistant TB patients treated in Tashkent city included XDR-TB, male sex, increasing age, previous TB treatment, alcohol abuse, and associated comorbidities (cardiovascular and liver disease, diabetes, and HIV/AIDS). Reasons for these findings and programmatic implications are discussed.

Treatment Compliance of Multidrug Resistant Tuberculosis in Uzbekistan: Does Practice Follow Policy?

Compliance with treatment guidelines is essential to achieve successful outcomes in tuberculosis patients. Thus, we assessed if multidrug-resistant tuberculosis treatment practices from 2012-2018 in Uzbekistan were compliant with national guidelines in terms of regimens prescribed, weight-based drug dosages used, and documentation of treatment changes (such as prolongation of intensive phase, change of drugs, and their reasons) in the treatment card and Consilium form. A total of 1481 patients were included. Of them, only 25% received standardized regimens as per guidelines and the remaining received individualized regimens. There was an increasing trend in using standardized regimens from 2% in 2012 to 44% in 2018. Compliance to recommended weight-based drug dosages was observed in 85% of the patients during the intensive phase and 84% in the continuation phase-ranged 71-91% over the years. Prolongation of the intensive phase was done in 42% of patients. The treatment was changed in 44% of patients during the intensive phase and 34% of patients during the continuation phase. The documentation of treatment changes was suboptimal (42-75%) during the initial years (2012-2014); however, it improved significantly during later years (86-100%). Future research should explore reasons for non-compliance so that the quality of patient care can be improved.

Scaling Up Molecular Diagnostic Tests for Drug-Resistant Tuberculosis in Uzbekistan from 2012-2019: Are We on the Right Track?

Uzbekistan has a large burden of drug-resistant tuberculosis (TB). To deal with this public health threat, the National TB Program introduced rapid molecular diagnostic tests such as Xpert MTB/RIF (Xpert) and line probe assays (LPAs) for first-line and second-line drugs. We documented the scale-up of Xpert and LPAs from 2012-2019 and assessed whether this led to an increase in patients with laboratory-confirmed multidrug-resistant/rifampicin-resistant TB (MDR/RR-TB) and extensively drug-resistant TB (XDR-TB). This was a descriptive study using secondary program data. The numbers of GeneXpert instruments cumulatively increased from six to sixty-seven, resulting in annual assays increasing from 5574 to 107,330. A broader use of the technology resulted in a lower proportion of tests detecting Mycobacterium tuberculosis with half of the positive results showing rifampicin resistance. LPA instruments cumulatively increased from two to thirteen; the annual first-line assays for MDR-TB increased from 2582 to 6607 while second-line assays increased from 1435 in 2016 to 6815 in 2019 with about one quarter to one third of diagnosed patients showing second-line drug resistance. Patient numbers with laboratory-confirmed MDR-TB remained stable (from 1728 to 2060) but there was a large increase in patients with laboratory-confirmed XDR-TB (from 31 to 696). Programmatic implications and ways forward are discussed.

Factors associated with unfavourable treatment outcomes in people with HIV-associated tuberculosis in Armenia, 2015 to 2019.

To evaluate factors associated with tuberculosis (TB) treatment outcomes in human Immunodeficiency Virus-Associated (HIV) TB patients in Armenia, we conducted a nation-wide cohort study using routine programmatic data of all HIV-associated TB patients receiving TB treatment with first- or second-line drugs from 2015 to 2019. Data were obtained from the TB and HIV electronic databases. We analysed occurrence of the combined unfavourable outcome (failure, lost to follow-up, death and not evaluated) and death separately, and factors associated with both outcomes using Cox regression. There were 320 HIV-associated TB patients who contributed a total of 351 episodes of TB treatment. An unfavourable TB treatment outcome was registered in 155 (44.2%) episodes, including 85 (24.2%) due to death, 38 (10.8%) lost to follow up, 13 (3.7%) failure and 19 (5.4%) not evaluated. Multivariable analysis showed that receipt of Antiretroviral Treatment (ART) [ART start before TB treatment: adjusted hazard ratio (aHR)=0.3, 95% confidence interval (CI): 0.2-0.5, aHR=, 95% CI:, 95% CI:, 95% CI:TB meningitis (aHR=4.4, 95% CI: 1.6-11.9) increased the risk. The risk of death was affected by the same factors as above in addition to the low BMI (aHR=2.5, 95% CI: 1.3-4.5) and drug resistance (aHR=2.3, 95% CI: 1.0-5.4). In the subsample of episodes receiving ART, history of interruption of ART during TB treatment increased the risk of unfavourable outcome (aHR=2.1 95% CI: 1.2-3.9), while ART start during TB treatment was associated with lower risk of both unfavourable outcome (within first 8 weeks: aHR: 0.5, 95% CI: 0.3-0.9; after 8 weeks: aHR: 0.4, 95% CI: 0.2-1.0) and death (within first 8 weeks: aHR: 0.2, 95% CI: 0.1-0.4; after 8 weeks: aHR: 0.1, 95% CI: 0.01-0.3). The rates of unfavourable TB treatment outcomes, and death in particular, among HIV-associated TB patients in Armenia are high. Our findings emphasize the protective effect of ART and the importance of proper management of cases complicated by drug resistance or meningitis.