Patterns of daily oral HIV PrEP adherence among people who inject drugs in Ukraine: an analysis of biomarkers.

INTRODUCTION: Daily oral HIV pre-exposure prophylaxis (PrEP) with tenofovir/emtricitabine (TDF/FTC) is recommended for people who inject drugs (PWID) but coverage is low. The real-life effectiveness of PrEP among PWID is unknown as previous studies were conducted in controlled settings and mainly relied on self-report. Analysis of PrEP metabolites-tenofovir diphosphate (TFVdp) and emtricitabine triphosphate (FTCtp)-offers an objective measure of adherence. METHODS: To analyse longitudinal patterns of PrEP adherence among PWID in Ukraine, we used data from a community-based implementation trial conducted in Kyiv between July 2020 and March 2021 to test the efficacy of SMS reminders to improve adherence. Among 199 enrolled participants, 156 (78.4%) were retained through 6 months. Based on TFVdp/FTCtp levels assessed at 3 and 6 months, we identified groups with various adherence patterns (adherent at ≥2 doses/week, improved, worsened, non-adherent). Correlates of adherence were analysed using multinomial logistic regression. RESULTS: Most participants (53.8%, n = 84/156) had no detectable metabolites at both assessments; 7.1% (n = 11/156) were consistently taking ≥2 doses/week; 1.3% (n = 2/156) were consistently taking ≥4 doses/week; 13.5% (n = 21/156) exhibited improved and 21.8% (n = 34/156) had worsened adherence at 6 compared to 3 months. "White coat compliance" (increased dosing prior to assessment) was common. Consistent adherence was associated with SMS reminders, younger age, employment, lower income, longer injection drug use duration, recent high-risk injecting (receptive syringe sharing, using pre-filled syringe, back- or front-loading, container sharing), absence of overdose in the past 6 months, perceived HIV risk through sexual intercourse and higher PrEP self-efficacy. Alcohol consumption was associated with inconsistent PrEP use. Groups with improved and worsened adherence did not differ. CONCLUSIONS: Daily oral PrEP may not achieve the desired effectiveness among PWID as a standalone intervention, calling for testing of alternative PrEP formulations and innovative integrated risk reduction strategies, especially in the context of HIV epidemics associated with injection drug use in eastern Europe and central Asia and the public health crisis in Ukraine caused by the war with Russia. SMS reminders may be effective among PWID who prioritize PrEP. Our findings offer practical guidance in identifying PWID who are likely to benefit from PrEP and those who need additional support.

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.

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.

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.

Stigma and quality of co-located care for HIV-positive people in addiction treatment in Ukraine: a cross-sectional study.

INTRODUCTION: Co-located treatment for HIV and opioid use disorder has been shown to improve care outcomes for HIV-positive people who inject drugs (PWID) in Ukraine. However, patients continue to be stigmatized for both HIV and substance use. This study aimed to assess whether co-located care for HIV-positive PWID receiving opioid agonist treatment (OAT) services in Ukraine is associated with less stigma and better perceived quality of HIV services. METHODS: This cross-sectional study enrolled 191 HIV-positive PWID who received OAT services at three healthcare facilities providing substance use treatment (OAT only) and at four facilities that provided co-located care (both OAT and HIV treatment) in six regions in Ukraine during July-September, 2017. Primary outcomes were HIV stigma (Berger scale), substance use stigma (Substance Abuse Stigma Scale) and intersectional stigma (both stigma forms above 75th percentile). Secondary outcome was quality of HIV care, a composite score based on a package of received services. Linear and ordinal regressions were used to assess the predictors of selected outcomes. RESULTS: Study participants were 75% male, mean age 40 ± 7 years; 47% received co-located care, and 10.5% had both high HIV and substance use stigma. Co-located care was neither associated with HIV nor substance use stigma but it was linked to better quality of HIV care (adjusted odds ratio: 4.13; 95% CI: 2.31, 7.54). HIV stigma was associated with suicide attempts (adjusted beta (aß): 5.90; 95% CI: 2.05, 9.75), and substance use stigma was linked to poor mental health (aß: -0.26; 95% CI: -0.44, -0.08) and lower likelihood of receipt of services from non-governmental organization (NGO; aß: -6.40; 95% CI: -10.23, -2.57). CONCLUSION: One in ten people with HIV in this cohort who received OAT services experienced high levels of both HIV and substance use stigma, which was associated with poorer mental health and less NGO support. Co-located HIV and OAT services were linked to better perceived quality of HIV care, but did not seem to reduce stigma for this key population. Stigma interventions for PWID, possibly delivered involving NGOs, may be an approach to mitigate this challenge.

Patients' perspectives of tuberculosis treatment challenges and barriers to treatment adherence in Ukraine: a qualitative study.

OBJECTIVES: To understand the challenges faced by patients with tuberculosis (TB) and factors that influence TB treatment adherence in Ukraine. DESIGN: Qualitative study. SETTING: TB treatment facilities in Kyiv Oblast, Ukraine. PARTICIPANTS: Sixty adults who had undergone treatment for drug-sensitive TB between June 2012 and August 2015. METHODS: We conducted semistructured, in-depth, individual interviews among a purposively selected clinical sample of patients previously treated for drug-sensitive TB. Interview content encompassed WHO's framework for barriers to adherence to long-term therapies and included questions about patient preferences and motivators concerning treatment adherence. We examined treatment experience across strata defined by previously identified risk correlates of non-adherence. RESULTS: Among 60 participants, 19 (32.8%) were HIV positive, 12 (20.3%) had substance use disorder and 9 (15.0%) had not completed TB treatment. Respondents discussed the psychological distress associated with hospital-based TB care, as well as perceived unsupportive, antagonistic interactions with TB providers as major challenges to treatment adherence. An additional barrier to successful treatment completion included the financial toll of lost income during TB treatment, which was exacerbated by the additional costs of ancillary medications and transportation to ambulatory TB clinics. The high pill burden of TB treatment also undermined adherence. These challenges were endorsed among participants with and without major risk factors for non-adherence. CONCLUSIONS: Our findings highlight important barriers to TB treatment adherence in this study population and suggest specific interventions that may be beneficial in mitigating high rates of poor treatment outcomes for TB in Ukraine.