The Effect of FOXP3+Regulatory T Cells on Infectious and Inflammatory Diseases

CD4+CD25+FOXP3+regulatory T cells (Tregs) contribute to the maintenance of immune homeostasis and tolerance in the body. The expression levels and functional stability of FOXP3 control the function and plasticity of Tregs. Tregs critically impact infectious diseases, especially by regulating the threshold of immune responses to pathogenic microorganisms. The functional regulatory mechanism and cell-specific surface markers of Tregs in different tissues and inflammatory microenvironments have been investigated in depth, which can provide novel ideas and strategies for immunotherapies targeting infectious diseases.Copyright © 2021. All rights reserved.

2022 IDSOG Annual Meeting, Boston, MA, 4-6 August 2022

This journal issue includes s of papers presented at the conference. Topics discusses are: stillbirth during a pandemic;analysis of the female genital tract (FGT) metabolome;effectiveness of REGEN-COV antibody combination to reduce risk of hospitalization;patterns of nucleic acid amplification testing;delta variant neutralizing antibody response following maternal COVID19 vaccination;integrated prenatal and hepatitis c virus care increases linkage;extended interval gentamicin dosing in obstetrics;maternal and infant cytomegalovirus detection among women living with HIV.

Scaling and Sustaining Facilitated Telemedicine to Expand Treatment Access Among Underserved Populations: A Qualitative Study.

Background: Opioid treatment programs are an essential component of the management of opioid use disorder (OUD). They have also been proposed as "medical homes" to expand health care access for underserved populations. We utilized telemedicine as a method to increase access for hepatitis C virus (HCV) care among people with OUD. Methods: We interviewed 30 staff and 15 administrators regarding the integration of facilitated telemedicine for HCV into opioid treatment programs. Participants provided feedback and insight for sustaining and scaling facilitated telemedicine for people with OUD. We utilized hermeneutic phenomenology to develop themes related to telemedicine sustainability in opioid treatment programs. Results: Three themes emerged on sustaining the facilitated telemedicine model: (1) Telemedicine as a Technical Innovation in Opioid Treatment Programs, (2) Technology Transcending Space and Time, and (3) COVID-19 Disrupting the Status Quo. Participants identified skilled staff, ongoing training, technology infrastructure and support, and an effective marketing campaign as key to maintaining the facilitated telemedicine model. Participants highlighted the study-supported case manager's role in managing the technology to transcend temporal and geographical challenges for HCV treatment access for people with OUD. COVID-19 fueled changes in health care delivery, including facilitated telemedicine, to expand the opioid treatment program's mission as a medical home for people with OUD. Conclusions: Opioid treatment programs can sustain facilitated telemedicine to increase health care access for underserved populations. COVID-19-induced disruptions promoted innovation and policy changes recognizing telemedicine's role in expanding health care access to underserved populations. ClinicalTrials.gov Identifier: NCT02933970.

A Cross-Sectional Survey on the Post-Pandemic Acceptability of Pharmacist-Delivered Telehealth Services Among HCV-HIV Patients.

The COVID-19 pandemic enhanced the use of telehealth as a means of delivering services to patients who required continued and uninterrupted care. This helped to reduce readmission to hospitals where COVID-19 hospitalization was prioritized. Patients with HCV and HIV and other chronic diseases require this type of care. This study evaluated the post-pandemic acceptability of pharmacist-delivered telehealth services among HCV and HIV monoinfected and coinfected patients in Washington DC. This was a cross-sectional study conducted in a community pharmacy setting in Washington DC whose primary outcome was the acceptability of pharmacist-delivered telehealth services through a proposed platform(docsink). A validated questionnaire, borrowed from the literature was used to determine telehealth acceptability, measured as behavioral intention, among patients who receive care from this pharmacy. The study recruited 100 participants. Descriptive statistics were conducted as well as bivariable and multivariable analyses to assess predictors of telehealth acceptability. In the unadjusted model, PU/EM (OR 0.571, 95% confidence interval (0.45-0.73), P < .0001)), PEOU(OR 0.72, 95% confidence interval (0.61-0.85)) and IM(OR 0.733, 95% confidence interval (0.62-0.87), P = .0003)) were significant predictors of behavioral intention. Overall, the study found that lower Perceived Usefulness/Extrinsic Motivation scores decrease the odds of intending to use pharmacist-delivered telehealth (OR = 0.490, 95% confidence interval (0.29-0.83), P = .008). This study determined that the impact of perceived usefulness and extrinsic motivation was critical to the acceptance of pharmacist-delivered telehealth among a predominantly Black/African American study population.

Countermeasures against viral hepatitis in Japan: road to HCV elimination

The World Health Organization (WHO) has set a goal of elimination of viral hepatitis by 2030. In Japan, the estimated people of chronic hepatitis C virus (HCV) and hepatitis B virus (HBV) infections were 1.7-2.2 and 1.3-1.5 million in 2000, respectively. Although the mortality due to hepatocellular carcinoma (HCC) had been increasing until around 2002, it has been gradually decreasing to date, and approximately 24,000 people died from HCC in 2021 in Japan. Japan has a national action plan for addressing viral hepatitis called, ''Basic Act on Hepatitis Measures'', established in 2009. ''Basic Guidelines for Promotion of Control Measures for Hepatitis'' was issued in 2011 and was updated in 2016 and 2022, comprising 9 principles in order to promote measures to prevent HBV and HCV. According to these guidelines, national and local government share screening costs for testing HBV and HCV for those residents who are over 40 years old. Thus, out-of-pocket expenses from examinees are free of charge or reduced to a minimum. In addition, for patients with chronic HBV or HCV infections treated with nucleotide analogues, interferon, and direct antiviral agents, the drug prices and examination expenses were covered by a medical-expenses support system for viral hepatitis. By these countermeasures against viral hepatitis, the estimated people of chronic HCV infection revealed a decrease to 1.0-1.6 million in 2011 (30-40% decrease from 2000 level) and 0.9-1.3 million in 2015 (40- 50% decrease from 2000 level). If the current situation had been continuing, the number of HCV patients is expected to decrease to 0.2-0.5 million (80-90% decrease from 2000 level and 60-80% decrease from 2015 level) by 2030. However, the COVID-19 pandemic since December 2019 is thought to have affected testing, linkage to care, treatment uptake, and follow-up, and new efforts that do not slow the progress to date toward HCV elimination, which is finally becoming visible, will be necessary in the future. In this lecture, I would also like to talk about the efforts at our hospital to achieve the sustainable development goal targeted by WHO.

Cooperate with community health centers to eliminate HCV in low prevalence region of South China

Background: Shenzhen, a city of immigrants in South China, has a low HCV incidence rate of 19.47 per 100,000. To eliminate HCV in this low prevalence region, it may be efficiency to collaborate with the communities to screen HCV in high risk population. There are 849 Community Health Centers up to now in Shenzhen. The study aimed to evaluate the model of HCV elimination in high-risk population with Community Health Centers. Method(s): The Shenzhen Medical Association assigned hepatologists to educate Primary Care Physicians (PCPs) of 13 Community Health Centers in Bao'an District from 2021.6-2022.6. The PCPs need to take HCV knowledge tests before and after the training. Only when all the questions are answered correctly can the test be passed. Then they recommend the high risk population, e.g., PWID, pricking wound, iatrogenic exposure, to do the HCV antibody test and transfer the patients with HCV-Ab (+) to the hepatologist of Shenzhen Bao'an People's Hospital. Result(s): 151 PCPs participated in HCV knowledge education, the pass rate improved from 15.2% to 53.8% after the training. The high risk population screening number in Community Health Centers improved from 192 (a year before) to 300, even affected by the lockdown of COVID-19. The HCV antibody positive rate in high risk population is 4% (12/300), higher than the hospital population (0.8%, Shenzhen Bao'an People's Hospital), the blood donor (0.3%, Shenzhen Blood Center). The HCV-Ab positive patients in communities transferred to Shenzhen Bao'an People's Hospital, where the rate of DAA treatment is improved from 36.6% (a year before) to 64.1%. Conclusion(s): It is an efficient way to achieve HCV elimination earlier to screening in high risk population through PCPs in low prevalence region. Expanding this model to other Community Health Centers in Shenzhen may accelerate HCV elimination. (Figure Presented).

Real world experience of drug-drug interactions for HCV patients receiving pan-genotypic direct-acting antivirals in the era of COVID-19 pandemic

Background and Aims: The treatment of chronic hepatitis C (CHC) has evolved from genotype-specific to pan-genotypic direct acting antivirals (DAAs) with high efficacy and safety. However, drug-drug interactions (DDIs) must be avoided when used in combination with other medications, especially with the possible concomitant use of COVID-19 infection antivirals during the COVID-19 pandemic. This study aimed to access the potential DDIs of concomitant drugs with pan-genotypic DAAs and COVID-19 infection antivirals, and actual incidence of DDIs in real-world experience. Method(s): From January 2022 to October 2022, consecutive 116 HCV patients receiving pan-genotypic DAAs were retrospectively enrolled in Taipei Veterans General Hospital. The number of comedications and their potential DDIs with three pan-genotypic DAA regimens and three COVID-19 infection antivirals were analyzed. The actual incidence of DDIs during DAAs treatment were also investigated. Result(s): The mean age was 60.9 years old, with male predominant (55.2%). Of them, 12 (10.3%) patients had cirrhosis, and 24 (20.7%) patients had diabetes mellitus. Most patients were within Child-Pugh class A (109/116, 94.0%). The distribution of HCV genotypes was 8.6% in GT 1a, 36.2% in GT 1b, 39.7% in GT 2, 6.9% in GT 6, and 8.6% in indeterminate genotype, respectively. Of them, 43 (37.1%) patients received GLE/PIB, 69 (59.5%) received SOF/VEL 7plusmn;RBV, and 4 (3.4%) received SOF/VEL/VOX as DAAs regimen. Noteworthy, four patients had COVID-19 infection during DAAs treatment course. The rates of ETVR and SVR12 were 97.6% and 95.3%. The mean number of concomitant medications was 2.01. The distribution of concomitant drugs was 64.7% with no concomitant drug, 11.2% with 1-3 drugs, 11.2% with 4-6 drugs, 9.5% with 7-9 drugs, and 3.4% had more than 9 drugs, respectively. In potential contraindicated (red) DDI class, GLE/PIB was the most prevalent (7.3%), followed by SOF/VEL/VOX (6.4%), and SOF/VEL (1.8%) for non-cirrhosis and compensated cirrhosis patients;and no red DDI occurred in decompensated cirrhosis patients. In addition, the percentage of patients without potential DDIs was higher with SOF/VEL (79.8%) than with the other regimens. The potential red DDIs were predominantly with lipid-lowering agents for DAAs. For potential red DDI class with COVID-19 infection antivirals, Nirmatrelvir/Ritonavir was the most prevalent (6%), followed by Remdesivir (0.9%), and no potential DDIs with Molnupiravir. For COVID-19 antivirals, the potential red DDIs was mainly with central nervous system drugs. Finally, the actual incidence of DDIs during DAAs treatment showed no red DDI occurred for all patients, and GLE/PIB was the most prevalent (93%) of no potential DDIs. Conclusion(s): The potential DDIs between these comedications differed, with the most potential DDIs occurring with GLE/PIB and Nirmatrelvir/Ritonavir. After careful assessment of comedications and their potential DDIs, the actual incidence of DDIs could be reduced, and optimize safety in real-world practice.

Taiwan's national strategies and actions toward HCV elimination before 2025

In 1990, the seroprevalence of antibody against hepatitis C virus (anti- HCV) in Taiwan was first documented to be 0.95% in volunteer blood donors, 90% in hemophiliacs, and 81% in parenteral drug abusers. The risk factors for HCV infection in Taiwan include iatrogenic transmission (medical injection, hemodialysis, acupuncture, and blood transfusion), tattooing, and sexual transmission. The long-term risk of hepatic and non-hepatic diseases has been well-documented by REVEL-HCV study. A national program of antiviral therapy for chronic viral hepatitis was launched in Taiwan in 2003. Mortality rates of end-stage liver diseases decreased continuously from 2000-2003 to 2008-2011 in all age and gender groups. When the World Health Assembly adopted the Global Health Sector Strategy on Viral Hepatitis in 2016, National program to eliminate hepatitis C was very carefully evaluated. It became a consensus to reach the WHO's 2030 goals in 2025. Taiwan Hepatitis C Policy Guideline 2018-2025 was approved and published at the beginning of 2019. There are triple focuses of hepatitis C elimination in Taiwan including (1) therapy spearheads prevention, (2) screening supports therapy, and (3) prevention secures outcome. A total of US$1.7 billion will be allocated from 2017 to 2025 for the elimination of HCV. The coverage of HCV screening and treatment has been increasing significantly since 2017. The HCV screening coverage was almost 100% for dialytic patients, 96% for HIV-infected patients, 65% for patients under opioid substitution treatment, 63% for patients in the pre-end-stage renal disease care program, 57% for patients in the early chronic kidney disease care program, 52% for patients in diabetes care program, 39% for prisoners, and 38% for adults aged 45-79 years old in the general population by April 30, 2020. The budget to cover the cost of DAA increased from US$101 million in 2017 to US$219 million in 2019. The number of chronic hepatitis C patients receiving DAA therapy increased from 9,538 in 2017, 19,549 in 2018, to 45,806 in 2019. However, the number of DAA-treated CHC patients reduced to 36,159 in 2020 and 20,559 in 2021 due to the COVID-19 pandemic. The cure rate based on SVR12 was 96.8% in 2017, 97.4% in 2018, over 98.6% after 2019. It is expected that Taiwan will achieve WHO's HCV elimination goal by 2025.

Changes in Disease Etiology of Deceased Donor Liver Transplantations Following Acuity Circles Policy Implementation

Introduction: The Acuity Circles (AC) allocation policy was implemented on February 4, 2020, with the primary intent of reducing disparities in access to deceased donor liver transplants (DDLTs). Overall, it has been successful at achieving this goal. However, changes in end-stage liver disease etiology following the policy change have not been well-characterized. Our goal was to understand how primary etiology of disease in DDLTs has changed since implementation of AC. Method(s): Data from the Organ Procurement Transplantation Network (OPTN) and United Network of Organ Sharing (UNOS) were analyzed to compare the primary classified etiologies of liver disease for DDLTs overall and based on allocation Model-for-end-stage-liver-disease (aMELD) categories used for AC sharing: aMELD>=37, aMELD 33-36, aMELD 29-32, aMELD 15-28, and aMELD<=14 DDLTs. Time was divided into four equivalent "eras" of 256 days duration by date of transplantation: 1) 9/10/18-5/23/19 (Era 1);2) 5/24/19-2/3/20 (Era 2);3) 2/4/20-10/16/20 (Era 3);and 4) 10/17/20-6/29/21 (Era 4). Result(s): The percentage of all DDLTs for alcohol-related liver disease (ARLD) increased from 32.3% pre-AC to 38.7% of DDLTs post AC. This was met with a corresponding decrease in the relative percentage of DDLTs related to Hepatitis C Virus (from 17.0% of DDLTs pre-AC to 12.2% post-AC), with the relative differences of other etiologies being a less than 1% difference pre- vs post- AC. There is a consistent increase in the share of DDLTs due to ARLD across each Era. The rise in adult DDLTs for ARLD was most pronounced among aMELD >=37 recipients, although similar trends were seen among aMELD 33-36 and aMELD 29-32 groups, but not aMELD 15-28 and aMELD <=14 groups. The median age of adult DDLTs for ARLD decreased consistently over time for the aMELD >=37 group, but not for the aMELD 33-36 and aMELD 29-32 groups. (Figure) (Table) Conclusion(s): Following implementation of AC, there was a relative increase in DDLTs due to ARLD. The younger age and high aMELD scores of these patients suggests these may be largely among patients with acute alcoholic hepatitis. This would align with published data on the overall increase in liver transplantation due to ARLD during the COVID-19 pandemic. (Figure Presented).

Outcomes of LEGA-C programs: a review of implementation science projects toward HCV elimination by 2030 in Asia

Background and Objectives: The WHO has identified HCV infection as a public health threat and set a global target for HCV elimination by 2030, yet currently only 11 countries are on track to achieve HCV elimination targets. Up to 60% of HCV + patients are lost to follow-up and remain untreated and this has likely been further exacerbated by the COVID-19 pandemic, which may have reduced HCV treatment urgency, causing many patients to delay care. To achieve the WHO goal, still many patients need to be screened and linked to care. Gilead has been running Local Elimination Programs Leading to Global Action in HCV (LEGA-C) to support implementation science projects toward HCV elimination. Here, we explore the outcomes of LEGA-C programs for patients with HCV especially in Asia. Method(s): The outcomes and impact were measured through the number of studies and patients to be reached;steps in the care cascade as well as efficacy of each model were assessed along with the presentations and publications from each study. Result(s): In total,[120 studies were supported. Of these, 18 have completed or are ongoing in Asia. Through July 2022, 175,192 persons were screened, 6,287 were HCV + and enrolled in a study, and 3,768 received treatment. A simplified screening and linkage to care/ minimal monitoring model was investigated in 8 studies and demonstrated that linkage to care with minimal monitoring could achieve antiviral response comparable to standard practice.[i] Four test-and-treat studies showed that aggressive screening and on-site treatment promotes HCV microelimination.[ii] Three outreach-andcallback studies showed demonstrated the feasibility of recruiting persons to HCV screening programs in community settings.[iii] Seven studies focused on special populations, and 4 of them described the characteristics of special populations with higher rates of HCV infection. Publications from these studies in Asia include 14 full articles, and these papers were cited a total of 56 times. Conclusion(s): The ongoing LEGA-C initiative is demonstrably contributing to the understanding, treatment, and ultimate elimination of HCV. Innovative ideas, active promotion of HCV testing, disease education, patient navigation, and care coordination in these programs led to increased screening and rates of linkage to care. Adopting and adapting effective strategies from these programs may be a feasible way to increase treatment numbers and improve patient outcomes, thus contributing to meeting the WHO goal of HCV elimination in Asia.

The impact of COVID-19 pandemic on the elimination program of viral hepatitis in Egypt

The severe acute respiratory syndrome coronavirus-2 (SARS CoV-2) infection and associated (COVID-19) pandemic disrupted the healthcare systems of most countries because of the overwhelming demand for COVID-19 care and the ensuing diversion of resources and public attention to this purpose. The WHO goals for HBV and HCV elimination are thus facing major hurdles regarding both screening and treatment, and are at risk of failure. Because of the pandemic, hospital liver care departments have reallocated health professionals and reduced or suspended outpatient care. Hepatitis elimination programs and interventions (screening, diagnosis, and treatment) have been reduced or halted altogether. The Egyptian Liver Research Institute and Hospital (ELRIAH) reported a reduction during 2020 vs. 2019 of 57.0% for HCV consultations and 87.2% for new referrals. In addition, Requests for HCV RNA testing were greatly affected, with 60.7% reduction in HCV RNA test requests between 2019 and 2020 with a drop of 86.9% in the number of HCV RNA-positive patients detected. In terms of HCV treatment rates;86.2% fewer patients with HCV started on antiviral treatment during the pandemic period compared to the year before. Regarding HBV, the reduction between 2019 and 2020 was 43.7% for consultations and 7.3% for new referrals. As a consequence, the number of HBsAg-positive individuals observed in ELRIAH decreased by 8.7%. Also, the requests for HBV testing were found to be highly affected. Consequently, the number of patients with detectable HBV DNA dropped by 8.3% and HBV treatment rates also decreased. In conclusion, the COVID-19 pandemic has had a significant impact on every step of the viral hepatitis cascade of care. Furthermore, HCC surveillance programmes are mostly halted.

An Immunocompetent Adult With Adenovirus Hepatitis

Introduction: In the US there has been a recent outbreak of adenovirus hepatitis in the pediatric population. However, to our knowledge, there has been only one reported case of adenovirus hepatitis in an immunocompetent adult. We have identified another such case. Case Description/Methods: A 25 year old female with no medical history presented with abdominal pain, nausea, vomiting, diarrhea, and subjective fevers for two weeks and was found to have transaminitis 25-30x the upper limit of normal, which were: AST 791, ALT 542, ALP 92, and total bilirubin of 2.9. The patient reported no prior history of liver disease. She denied alcohol, tobacco, illicit drugs, or herbal medications, but did report taking acetaminophen 1500 mg daily for two weeks. Serum acetaminophen levels were normal and serum and urine toxicology were negative. US with doppler was unremarkable, CT showed cholelithiasis, MRCP showed a normal common bile duct without obstructive calculus. Autoimmune causes of hepatitis, ceruloplasmin and alpha-1 antitrypsin were all unremarkable. HAV, HBV, HCV, HDV, HEV, CMV, HSV, VZV, EBV, HIV, and COVID19 were all negative. Ultimately, the serology for adenovirus was positive. After a week of supportive treatment, the patient's labs trended down and symptoms resolved. Discussion(s): Adenovirus is confirmed by a rise in antibody titer or by virus detection. Coagulative necrosis in histopathology is a finding in liver biopsies if they are pursued in unexplained cases of liver injury. Ultimately, adenovirus hepatitis can be diagnosed once all common causes of hepatitis have been excluded. In the current outbreak, only children have been getting adenovirus hepatitis. In adults, a high prevalence of neutralizing antibodies contributes to immunity, and therefore only in immunocompromised states, do adults get such an infection. Supportive care with IV fluids, electrolyte correction, and antiemetics usually is enough with eventual symptomatic and laboratory improvement as it was for our patient. Studies have shown that extensive disease can be treated with antiviral drugs, cidofovir, and ribavirin. Our patient's history of acetaminophen use is a confounder, however, her normal serum level and her symptoms suggestive of an infectious cause made acetaminophen less of a culprit. We hypothesize that our patient's use of acetaminophen when she was initially exposed to the virus is what made her susceptible to developing adenovirus hepatitis and we hope this case adds insight for clinicians dealing with future adult cases.

Computer-Aided vaccine design for selected positive-sense single stranded RNA viruses

Spontaneous mutations and lack of replication fidelity in positive-sense single stranded RNA viruses (+ssRNA virus) result in emergence of genetic variants with diverse viral morphogenesis and surface proteins that affect its antigenicity. This high mutability in +ssRNA viruses has induced antiviral drug resistance and ability to overcome vaccines that subsequently resulted in rapid viral evolution and high mortality rate in human and livestock. Computer aided vaccine design and immunoinformatics play a crucial role in expediting the vaccine production protocols, antibody production and identifying suitable immunogenic regions or epitopes from the genome sequences of the pathogens. T cell and B cell epitopes can be identified in pathogens by immunoinformatics algorithms and methods that enhance the analysis of protective immunity, vaccine safety, immunity modelling and vaccine efficacy. This rapid and cost-effective computational vaccine design promotes development of potential vaccine that could induce immune response in host against rapidly mutating pathogens like +ssRNA viruses. Epitope-based vaccine is a striking concept that has been widely employed in recent years to construct vaccines targeting rapidly mutating +ssRNA viruses. Therefore, the present review provides an overview about the current progress and methodology in computer-aided vaccine design for the most notable +ssRNA viruses namely Hepatitis C virus, Dengue virus, Chikungunya virus and Coronaviruses. This review also highlights the applications of various immunoinformatics tools for vaccine design and for modelling immune response against +ssRNA viruses. © 2023, National Institute of Science Communication and Policy Research. All rights reserved.

Micro-eliminating HCV in 8 diverse prisons that serve a general population of 3.7 million in the Yorkshire region of England

Background: National Health Service England (NHSE) plans to eliminate Hepatitis C (HCV) by 2025. With a reported HCV prevalence of about 6% in male prisons, and about 12% in female prisons, secure environments are an essential component of this elimination plan. Yorkshire is a region in England with a general population of about 3.7 M. PPG is the provider of healthcare to 9 prisons in Yorkshire, with approximately 6,000 residents, many of whom are current, or previous, substance users. Description of model of care/intervention: To support NHSE in the elimination of HCV, a partnership between Gilead Sciences, Practice Plus Group (PPG) and the Hepatitis C Trust (HCT) was formed in 2019. This partnership works with prison and hospital teams to optimise test and treat pathways for new prison admissions. In addition, whole prison HCV Intensive Test and Treat events (HITT programmes) were run in targeted prisons to ensure testing of residents who were incarcerated before these optimisations were implemented. Effectiveness: HCV screening, within 7 days of prison entry, increased from 27% in May 2019 to 93% in January 2022. This increase was achieved despite COVID-19 restrictions remaining in place since March 2020 across all English prisons. In addition, HITT programmes were used to test residents who were missed at prison entry. The overall result is that 8/9 prisons have achieved microelimination status, as defined by: >= 95% of prison residents tested within the previous 12 months, >= 90% of RNA positive patients treated or initiated on treatment and presence of a robust system to review ongoing testing and treatment performance to ensure these targets are maintained. Conclusion and next steps: Micro-elimination of HCV will now need to be maintained in these prisons by ensuring the uptake of HCV testing remains>95%. Plans are in place to micro-eliminate the final prison-which is a high-security prison presenting unique challenges to HCV micro-elimination.

SEXUAL BEHAVIOR AND STI INCIDENCE DURING THE FIRST 4 YEARS OF PrEP USE AMONG MSM

Background: A prospective demonstration project in Amsterdam (AMPrEP) provided pre-exposure prophylaxis (PrEP) to people vulnerable to HIV in 2015- 2020. Data on long-term trends in sexual behavior and incidence of STIs during PrEP use are needed to inform future PrEP programs. Therefore, we assessed sexual behavior and incidence rates of STIs among MSM and transgender women on PrEP over four years. Method(s): AMPrEP participants chose between oral PrEP daily (dPrEP) or event-driven (edPrEP) at baseline and could switch regimens at each 3-monthly study visit. They were tested for STIs at these visits and if necessary in between. Follow-up began at PrEP initiation and continued until 48 months of follow-up or was censored at March 15, 2020 (start COVID-19), whichever occurred first. We assessed changes over time in incidence rates (IR) of chlamydia, gonorrhea, and infectious syphilis using Poisson regression. We estimated the IR of Hepatitis C (HCV) diagnoses per consecutive year. We described the number of HIV diagnoses, and sexual behavior (i.e. number of sex partners, condomless anal sex acts with casual partners [CAS]). Result(s): A total of 367 (365 MSM) started PrEP and contributed 1249 person-years of observation. IRs of any STI was 87[95%CI 82-93]/100PY. There was no change in the IR of any STI and infectious syphilis over time on PrEP. We observed a slight decrease in incident chlamydia and gonorrhea in daily PrEP users (Table). Two incident HIV cases were diagnosed in the first year of follow-up. IRs for HCV were 1.5[0.6-3.6], 2.5[1.3-5.0], 0.7[0.2-2.7], and 0.4[0.1- 2.8]/100PY, per consecutive year on PrEP. Median number of sex partners per 3-month period decreased from 16[IQR 8-34] and 12[6-25] (dPrEP and edPrEP, respectively) at baseline, 15[7-30] and 8[3-16] at 24 months, and 12[6-26] and 5[2-12] at 48 months. Median number of CAS acts with casual partners were respectively 7[3-15] and 4[1-9] at baseline, 14[5-25] and 4[1-12] at 24 months, and 12[4-25] and 4[1-9] at 48 months. Conclusion(s): Over the first 4 years of PrEP use overall STI incidence was high and stable. Chlamydia and gonorrhea incidence declined slightly in daily users. Numbers of sex partners seemed to decrease in both dPrEP and edPrEP users. Number of CAS acts with casual partners appeared to increase first, and then stabilized. Notably, this did not result in increased incidence of STIs. Regular testing and treatment of STIs remain a priority among PrEP users. Biomedical prevention of STIs can be examined in this context.

Plitidepsin Is a Broad-Spectrum Antiviral Shaping the Cell Proteostatic Balance

Background: Different viruses employ similar pathways for replication, revealing key intracellular hotspots to target with host-directed therapies and achieve a broad-spectrum antiviral activity. Plitidepsin is a clinically approved antitumoral agent that blocks the elongation factor eEF1A required for protein translation. This drug counteracts SARS-CoV-2 replication and shows a favorable safety profile in COVID-19 patients. Yet, the precise antiviral mechanism of action of plitidepsin remains unknown. Method(s): Here we used a deep quantitative proteomic analysis to measure the impact of plitidepsin on the proteome of SARS-CoV-2-infected Vero E6 cells. This was complemented with transmission electron microscopy assays, which unraveled the subcellular and morphological changes associated to plitidepsin treatment. In addition, we performed functional in vitro assays to dissect the antiviral activity of plitidepsin against SARS-CoV-2 and other viruses. Result(s): We found that this drug inhibited the synthesis of all SARS-CoV-2 proteins in a dose-dependent manner. These included the R1AB polyproteins, which facilitate the synthesis of non-structural proteins involved in the formation of double membrane vesicles (DMV) required for viral replication. Plitidepsin reduced DMV formation and the morphogenesis of new viruses, having a greater impact on viral than on host proteins. Less than 14% of the cellular proteome was significantly affected by plitidepsin, inducing the up-regulation of key molecules associated with protein biosynthesis, such as the translation initiation factors eIF4A2 and eIF2S3. Therefore, plitidepsin induced a compensatory state that rescued protein translation. This proteostatic response explains how cells preserve the cellular proteome after treatment with a translation inhibitor such as plitidepsin. In addition, it suggests that plitidepsin could inhibit other RNA-dependent and non-integrated DNA viruses, as we confirmed in vitro using Zika virus, Hepatitis C virus replicon and Herpes simplex virus. However, the compensatory proteostasis induced by plitidespin also explains why this drug failed to inhibit the replication of integrated DNA proviruses such as HIV-1. Conclusion(s): Unraveling the mechanism of action of host-directed therapies like plitidepsin is imperative to define the indications and antiviral profile of these compounds. This knowledge will be key to develop broad-spectrum treatments and have them ready to deploy when future pandemic viruses break through.

Hepatitis C Burden in Greece, Italy, Portugal, and Spain: 2000-2019

Background: Viral Hepatitis remains a health priority. We performed a comprehensive evaluation of epidemiological HCV estimates in Southern countries of Western Europe and assessed the impact of the 2008 economic crisis on HCV burden. Method(s): We analyzed data of the Global Burden of Diseases to describe the patterns of six measures of HCV burden [prevalence, incidence, mortality, years lived with disability (YLDs), years of life lost (YLLs), disability adjusted life years (DALYs)] in Greece, Italy, Portugal, Spain. We assessed age-standardized rates (per 100,000 population) between 2000-2019, disaggregated by sex and age, and compared the annualized age-standardized rate of change (ARC%) in 2000-2010 (pre-austerity) and 2010-2019 (post-austerity). Result(s): Prevalence, incidence and YLDs rates of acute HCV showed a general stable trend in Western Europe (WE), globally and in the four studied countries except Italy, where, despite a marked decline (ARC: 1.4% in 2010-2019), the 2019 estimates [7.8 (95% UI 6.6-9.2)] were still 1.7-fold higher than in WE. Mortality, YLLs and DALYs associated with acute HCV decreased in the analyzed countries and peaked in Greece post-austerity. Globally and in Greece, mortality rate was higher in females than in males (1.3-times and 1.5-times in 2019, respectively). Mortality caused by chronic liver diseases including cirrhosis decreased globally, in WE and in all countries albeit at a lower rate in the post-austerity period (decrease in ARC for WE: 2.5% in 2000-2010;1.6 in 2010-2019). Liver cancer prevalence due to HCV increased in WE (ARC: 2.1%) and in the analyzed countries mainly in the pre-austerity period except for Italy. However, despite having the highest prevalence rate in both sexes, Italy showed major decreases in all six-disease metrics. HCV liver cancer mortality declined significantly only in Italy (ARC: 2.6%) and globally (ARC: 2.1%) especially in the pre-austerity period, while Portugal experienced a major increase postausterity. Overall, males and people over 70 years old are at greater risk of developing chronic liver diseases due to HCV infection. Conclusion(s): The economic crisis of 2008 negatively impacted hepatitis C related liver cancer mortality rates in Greece, Italy, Portugal and Spain. Despite the observed recovery in recent years, elimination of HCV infection by 2030 will be a major challenge in these countries and the COVID-19 pandemic and the current grim economic context are expected to compromise even further hepatitis C elimination.

Comparison of the Effectiveness of Different Covid-19 Vaccines among Plwh

Background: Previous studies have demonstrated promising serologic responses in PLWH receiving a third dose of vaccine against SARS-CoV-2. However, real-world clinical effectiveness, especially during the pandemic caused by B.1.1.529 variant, remains less investigated. Method(s): PLWH seeking HIV care at our hospital from 2021/6 to 2022/6 were included and advised to receive the third dose of COVID-19 vaccine. Individuals were excluded from this study if they had been previously diagnosed with COVID-19. Different types of COVID-19 vaccines were available in the vaccination program, including BNT162b2, mRNA-1273 (either 50 or 100 mug), MVC-COV1901 and NVX-CoV2373 vaccines. PLWH were screening for the occurrence of COVID-19 through the reporting system of notifiable diseases of Taiwan CDC, and were tested for anti-nucleocapsid (anti-N) IgG every 1 to 3 months. Participants were followed for 180 days until the fourth dose of COVID-19 vaccination, occurrence of SARS-CoV-2 infection, seroconversion of anti-N IgG, death, or loss to follow-up, whichever occurred first. Result(s): 1,496 PLWH were included: 631 (42.2%) receiving 100 mug mRNA-1273 vaccine, 468 (31.3%) 50 mug mRNA-1273 vaccine, and 328 (21.9%) BNT162b2 vaccine, 65 (4.3%) MVC-COV1901 vaccine, and 4 (0.3%) NVX-CoV2373 vaccine for the third dose of SARS-CoV-2 vaccination. 297 (19.9%) PLWH were diagnosed with COVID-19 during the follow-up period, including 92 (14.6%) who received 100 mug mRNA-1273, 111 (23.7%) 50 mug mRNA-1273, 79 (24.1%) BNT162b2 and 15 (21.7%) either MVC-COV1901 or NVX-CoV2373;in addition, 98 PLWH had seroconversion of anti-N IgG during follow-up, including 23, 50, 19 and 6 PLWH who received 100 mug mRNA-1273, 50 mug mRNA-1273, BNT162b2, and either MVC-COV1901 or NVX-CoV2373, respectively. Similar rates of new infection with SARS-CoV-2 or seroconversion of anti-N IgG were demonstrated regardless the vaccine type of the third dose (log-rank test, p=0.46). Factors associated with a diagnosis of SARS-CoV-2 infection and seroconversion of anti-N IgG included an age >50 years (aOR, 0.67;95% CI, 0.49-0.91) and newly infected with hepatitis C virus (HCV) (aOR, 1.41;95% CI, 1.09-1.83). Conclusion(s): Our study demonstrated that clinical effectiveness of the third dose of different vaccines available to PLWH was similar in preventing SARSCoV- 2 infection or seroconversion of anti-N IgG Taiwan. PLWH aged less than 50 years and those with newly diagnosed HCV infection were at higher risk of acquiring COVID-19. Kaplan-Meier survival curve for acquiring COVID-19 or seroconversion of anti-N IgG in PLWH receiving different COVID-19 vaccination of the third dose (log-rank test, 4 groups, p = 0.46).

Transgender Women Baseline Profile in Transcitar: Transspecific Cohort in Argentina

Background: Transgender women (TGW) are among the population most affected by the HIV epidemic in Argentina, despite a progressive legal framework. TransCITAR is a trans-specific cohort in Argentina that aims to assess physical and mental health among transgender and non-binary people (TGNBP). We present baseline characteristics of TGW. Method(s): TGW attending a trans-friendly clinic to receive HIV/STIs prevention/ treatment, mental health care and/or gender-affirming hormone therapy (GHT) were invited to participate. Semiannual visits including clinical assessments, laboratory tests, and psychosocial interviews were performed. Oral PrEP was offered as part of a combined prevention strategy since September 2021. Result(s): Between September/2019 and August/2022, 500 TGNBP were enrolled, 416 were TGW (median age: 30 years, IQR 25-37). High social vulnerability was observed (Table 1). Regarding trans-specific characteristics, 49.8% reported industrial silicone injections and 36.8% were receiving GHT. 76.9% were sex workers. Baseline STIs prevalence were: HIV 42.3% (10.2% diagnosed at enrolment), syphilis 40% (defined as positive nontreponemal test VDRL with titers of at least 1/8), past HBV 18.5%, chronic HBV 3.8%, HCV antibody positive 2.6%. Only 57% presented HBV protective antibodies titers (HBVsAb>=10UI/ml), 8 TGW were on PreP. For those with HIV, median CD4+ cell count was 602 cells/mm3 (IQR 378-933), 66.5% were on ART at enrolment (53.6% were virally suppressed) and 14.8% initiated at baseline. During 36 months of follow up, 4 TGW died (one AIDS-related and one COVID-19-related). Bivariate analyses showed that a positive HIV diagnosis was independently associated with migration, low level of education, unstable housing, silicone injecion and sex work, while was negatively associated with being on GHT. In multivariable logistic regression, only sociodemographic variables remain associated: migrant (aOR=.487, 95% CI=.304-.768);incomplete high school (aOR=.463, 95% CI=.300=.714);unstable housing (aOR=.614, 95% CI=.401- .940);and sex work (aOR=.324, 95% CI=.177-.593). Conclusion(s): TGW from TransCITAR presented poor health outcomes: high prevalence of HIV/syphilis, high proportion with incomplete/no HBV vaccine and high levels of depression and violence. A comprehensive approach to care and addressing social determinants of health is pivotal to reduce HIV burden in this population.

TASL, TADE, and DAROC consensus for the screening and management of hepatitis C in patients with diabetes.

Diabetes mellitus (DM) and hepatitis C virus (HCV) infection are prevalent diseases globally and emerging evidence demonstrates the bidirectional association between the two diseases. Direct-acting antivirals (DAAs) for HCV have a high treatment success rate and can significantly reduce the risks of short and long-term complications of HCV infection. However, despite the evidence of the association between diabetes and HCV and the benefits of anti-HCV treatment, previously published guidelines did not focus on the universal HCV screening for patients with diabetes and their subsequent management once confirmed as having HCV viremia. Nonetheless, screening for HCV among patients with diabetes will contribute to the eradication of HCV infection. Thus, the three major Taiwan medical associations of diabetes and liver diseases endorsed a total of 14 experts in the fields of gastroenterology, hepatology, diabetology, and epidemiology to convene and formulate a consensus statement on HCV screening and management among patients with diabetes. Based on recent studies and guidelines as well as from real-world clinical experiences, the Taiwan experts reached a consensus that provides a straightforward approach to HCV screening, treatment, and monitoring of patients with diabetes.