Early disruptions to syringe services programs during the Russian invasion of Ukraine.

Introduction: The widespread HIV epidemic in Ukraine is concentrated among people who inject drugs (PWID), making access to sterile injection paraphernalia (SIP) like sterile needles and syringes a critical method of HIV/AIDS prevention; however, the Russian invasion has threatened to disrupt the operations of syringe services programs (SSPs), creating a risk of HIV outbreaks among PWID. Methods: We conducted 10 semi-structured interviews with outreach workers from SSPs. Interviews were purposively sampled to cover three prototypic regions of Ukraine: temporarily Russian-controlled, frontline, and destination. Qualitative results from interviews were then compared against a standardized, nationwide harm reduction database. Results: We found that the Russian invasion triggered both supply and demand challenges for SSPs. Demand increased for all regions due to client transitions from pharmacies that closed to SSPs, increases in illicit drug use, greater client openness to NGO support, and displacement of clients to destination regions. Supply decreased for all areas (except for remote destination regions) due to battle-related barriers like curfews, roadblocks, and Internet disruptions; diminished deliveries of SIP and funding; and staff displacement. Time series plots of the number of unique clients accessing harm reduction services showed that an initial decrease in service provision occurred at the start of the war but that most regions recovered within several months except for Russian-controlled regions, which continued to provide services to fewer clients relative to previous years. Conclusion: To ensure continued scale-up of SIP and other HIV prevention services, the SyrEx database should be leveraged to serve as a streamlined harm reduction locator that can inform workers and clients of open site locations and other pertinent information.

Leveraging existing provider networks in Europe to eliminate barriers to accessing opioid agonist maintenance therapies for Ukrainian refugees.

Russia's invasion of Ukraine caused a major refugee crisis, particularly impacting Central and Eastern Europe. Ukraine has one of the highest prevalence rates of opioid use disorder (OUD) in Europe, which increases the risk of HIV spread due to injection drug use. Opioid agonist maintenance therapies (OAMT) are a gold standard treatment for OUD and the prevention of HIV spread. Refugees who were displaced and previously maintained on OAMT in Ukraine require reliable care continuity, but OAMT is often highly regulated making it difficult to access. Using an implementation science lens, we sought to understand the barriers and facilitators that might impede OAMT continuity. We performed 23 semi-structured interviews with displaced patients with OUD and providers of OAMT and harm reduction. Interview participants were purposively sampled to include individuals from the highest-impacted countries: Poland, Germany, Czechia, Slovakia, Romania, and Hungary. Interviews focused on existing provider networks and barriers that refugees on OAMT faced during displacement. Though networks existed, there was little collaboration between providers and key stakeholders, such as NGOs, in overcoming barriers. Moreover, existing formal networks were not leveraged for rapid problem-solving. We found that despite existing networks, providers encountered substantial barriers to successfully coordinating access and retention in OAMT for refugees. Owing to insufficiently leveraged coordination between providers, clinics frequently turned patients away due to insufficient capacity, language barriers, and financial coverage issues. The limited geographic distribution of clinics in larger countries, such as Poland and Germany, further inhibited refugees from accessing and remaining on treatment. To support countries and providers in responding to a rapidly evolving crisis, collaborative learning combined with rapid cycle change projects used by the Network for the Improvement of Addiction Treatment (NIATx) model could be deployed to promote collaboration between providers both nationally and throughout the European Union to guide continuity of OAMT.

Changes in T-cell subsets and clonal repertoire during chemoimmunotherapy with pembrolizumab and paclitaxel or capecitabine for metastatic triple-negative breast cancer.

BACKGROUND: Chemoimmunotherapy is a standard treatment for triple-negative breast cancer (TNBC), however, the impacts of different chemotherapies on T-cell populations, which could correlate with clinical activity, are not known. Quantifying T-cell populations with flow cytometry and T-cell receptor (TCR) immunosequencing may improve our understanding of how chemoimmunotherapy affects T-cell subsets, and to what extent clonal shifts occur during treatment. TCR immunosequencing of intratumoral T cells may facilitate the identification and monitoring of putatively tumor-reactive T-cell clones within the blood. METHODS: Blood and tumor biopsies were collected from patients with metastatic TNBC enrolled in a phase Ib clinical trial of first or second-line pembrolizumab with paclitaxel or capecitabine. Using identical biospecimen processing protocols, blood samples from a cohort of patients treated for early-stage breast cancer were obtained for comparison. Treatment-related immunological changes in peripheral blood and intratumoral T cells were characterized using flow cytometry and TCR immunosequencing. Clonal proliferation rates of T cells were compared based on intratumoral enrichment. RESULTS: When combined with pembrolizumab, paclitaxel and capecitabine resulted in similar time-dependent lymphodepletions across measured peripheral T-cell subsets. Their effects were more modest than that observed following curative-intent dose-dense anthracycline and cyclophosphamide (ddAC) (average fold-change in CD3+ cells, capecitabine: -0.42, paclitaxel: -0.56, ddAC: -1.21). No differences in T-cell clonality or richness were observed following capecitabine or paclitaxel-based treatments. Regression modeling identified differences in the emergence of novel T-cell clones that were not detected at baseline (odds compared with ddAC, capecitabine: 0.292, paclitaxel: 0.652). Pembrolizumab with paclitaxel or capecitabine expanded T-cell clones within tumors; however, these clones did not always expand within the blood. Proliferation rates within the blood were similar between clones that were enriched and those that were not enriched within tumors. CONCLUSION: Chemoimmunotherapy for metastatic TNBC with pembrolizumab and capecitabine or paclitaxel resulted in similar peripheral T-cell subset lymphodepletion without altering T-cell clonal diversity. Regression modeling methods are applicable in immune monitoring studies, such as this to identify the odds of novel T-cell clones emerging during treatment, and proliferation rates of tumor-enriched T-cell clones.