Infectious Neuropathies

Infectious diseases frequently affect the peripheral nervous system by direct infiltration or indirect inflammatory response induced by the microorganisms. Peripheral neuropathies are commonly observed in the course of HIV infection and represent the major neurological complication of the disease. The heterogeneous spectrum makes the diagnosis challenging even for the expert neurologist and includes distal symmetric neuropathies, demyelinating neuropathies, mononeuritis multiplex, progressive polyradiculopathies, and diffuse infiltrative lymphocytosis syndrome. Peripheral neuropathy (PN) is one of the most frequently reported extrahepatic complications of HCV chronic infection, occurring in about 10% of HCV-infected patients. PN usually coexists with cryoglobulinemia and may manifest as chronic "length dependent” distal symmetrical sensorimotor or mainly sensory axonal polyneuropathy, "stocking-glove” asymmetric polyneuropathy, subacute mononeuropathy multiplex, or asymmetrical neuropathy involving large or small nerve fibers. Pure motor or demyelinating neuropathies and, rarely, cranial or autonomic neuropathies, have also been reported. Among the rarest causes of infectious neuropathies, leprosy and borreliosis are an important global health concern. The differential diagnosis is often difficult and sometimes, in particular in suspected neuritic form of leprosy, requires nerve biopsy and a detailed neuropathological analysis that can help for personalized therapy. With the COVID-19 pandemic, many cases of patients with peripheral nervous system involvement have been described, in the absence of a direct role of SARS-CoV-2. © Springer Nature Switzerland AG 2022.

Congenital infection (syphilis, aids, viral hepatitis and coronavirus) in pregnancy

Pregnancy may increase susceptibility to the infection diseases and associated increased mortality rates. In the present chapter, we wanted to discuss about clinical manifestations, laboratory diagnosis, management of the infection, prevention and prophylaxis of infections in pregnancy and perinatal period. We mainly focus on the congenital infections caused by the pathogens including human immunodeficiency virus (HIV), T. Pallidum, SARS-CoV-2 (Severe acute respiratory syndrome coronavirus 2) and viral hepatitis viruses (B, C, and E) that change maternal fetal out comes. © 2023 Nova Science Publishers, Inc. All rights reserved.

Antiviral Activity of Pyrimidine Containing Compounds: Patent Review.

Viruses are still the most prevalent infectious pathogens on a worldwide scale, with many of them causing life-threatening illnesses in humans. Influenza viruses, because of their significant morbidity and mortality, continue to pose a major threat to human health. According to WHO statistics, seasonal influenza virus epidemics are predicted to cause over 2 million severe illness cases with high death rates yearly. The whole world has been suffering from the COVID-19 epidemic for two years and is still suffering so far, and the deaths from this virus have exceeded three million cases. Because the great majority of viral infections do not have a specific medication or vaccination, discovering novel medicines remains a vital task. This review covers reports in the patent literature from 1980 to the end of 2021 on the antiviral activities of pyrimidine moieties. The patent database, SciFinder, was used to locate patent applications. A large variety of pyrimidine molecules have been produced and tested for antiviral activity over the last decade. These molecules were reported to inhibit a wide range of viruses, including influenza virus, respiratory syncytial virus, rhinovirus, dengue virus, herpes virus, hepatitis B and C, and human immunodeficiency virus. The cytotoxicity of the developed pyrimidine derivatives was tested in almost all reported studies and the selectivity index was calculated to show the selectivity and safety of such molecules. From the remarkable activity of pyrimidine compounds as antivirals for several dangerous viruses, we expect that these derivatives will be used as potent drugs in the very near future.

Humoral Immune Response after COVID-19 mRNA Vaccination in Patients with Liver Cirrhosis: A Prospective Real-Life Single Center Study.

Coronavirus-disease-2019 (COVID-19) mRNA vaccination effectively reduces mortality and morbidity in cirrhotic patients, but the immunogenicity and safety of vaccination have been partially characterized. The study aimed to evaluate humoral response, predictive factors, and safety of mRNA-COVID-19 vaccination in cirrhotic patients compared to healthy subjects. A prospective, single-center, observational study enrolled consecutive cirrhotic patients who underwent mRNA-COVID-19 vaccination from April to May 2021. Anti-spike-protein (anti-S) and nucleocapsid-protein (anti-N) antibodies were evaluated before the first (T0) and the second (T1) doses and 15 days after completing the vaccination. An age and sex-matched healthy reference group was included. The incidence of adverse events (AEs) was assessed. In total, 162 cirrhotic patients were enrolled, 13 were excluded due to previous SARS-CoV-2 infection; therefore, 149 patients and 149 Health Care Workers (HCWs) were included in the analysis. The seroconversion rate was similar in cirrhotic patients and HCWs at T1 (92.5% vs. 95.3%, p = 0.44) and T2 (100% in both groups). At T2, anti-S-titres were significantly higher in cirrhotic patients compared to HCWs (2776.6 vs. 1756 BAU/mL, p < 0.001]. Male sex (ß = -0.32 [-0.64, -0.04], p = 0.027) and past-HCV-infection (ß = -0.31 [-0.59, -0.04], p = 0.029) were independent predictors of lower anti-S-titres on multiple-gamma-regression-analysis. No severe AEs occurred. The COVID-19-mRNA vaccination induces a high immunization rate and anti-S-titres in cirrhotic patients. Male sex and past-HCV infection are associated with lower anti-S-titres. The COVID-19-mRNA vaccination is safe.

A people-centered decentralized outreach model toward HCV micro-elimination in hyperendemic areas: COMPACT study in SARS Co-V2 pandemic.

OBJECTIVES: Gaps in linkage-to-care remain the barriers toward hepatitis C virus (HCV) elimination in the directly-acting-antivirals (DAA) era, especially during SARS Co-V2 pandemics. We established an outreach project to target HCV micro-elimination in HCV-hyperendemic villages. METHODS: The COMPACT provided "door-by-door" screening by an "outreach HCV-checkpoint team" and an "outreach HCV-care team" for HCV diagnosis, assessment and DAA therapy in Chidong/Chikan villages between 2019 and 2021. Participants from neighboring villages served as Control group. RESULTS: A total of 5731 adult residents participated in the project. Anti-HCV prevalence rate was 24.0% (886/3684) in Target Group and 9.5% (194/2047) in Control group (P < 0.001). The HCV-viremic rates among anti-HCV-positive subjects were 42.7% and 41.2%, respectively, in Target and Control groups. After COMPACT engagement, 80.4% (304/378) HCV-viremic subjects in the Target group were successfully linked-to-care, and Control group (70% (56/80), P = 0.039). The rates of link-to-treatment and SVR12 were comparable between Target (100% and 97.4%, respectively) and Control (100% and 96.4%) groups. The community effectiveness was 76.4% in the COMPACT campaign, significantly higher in Target group than in Control group (78.3% versus 67.5%, P = 0.039). The community effectiveness decreased significantly during SARS Co-V2 pandemic in Control group (from 81% to 31.8%, P < 0.001), but not in Target group (80.3% vs. 71.6%, P = 0.104). CONCLUSIONS: The outreach door-by-door screen strategy with decentralized onsite treatment programs greatly improved HCV care cascade in HCV-hyperendemic areas, a model for HCV elimination in high-risk marginalized communities in SARS Co-V2 pandemic.

Voltammetric determination of daclatasvir dihydrochloride at bimetallic Ag/Co nanoparticles modified carbon paste electrode

In this work, a sensitive and cost-effective voltammetric method was proposed for the determination of daclatasvir dihydrochloride (DAC.2HCl) at a bimetallic Ag/Co nanoparticles-modified carbon paste electrode. Potential cyclization was used for the electro-deposition of the nanoparticles. The number of potential cycles needed for deposition was optimized. Surface characterization of the prepared sensor was performed using scanning electron microscope imaging (SEM). The electroanalysis of DAC was performed using cyclic voltammetry (CV) and differential pulse voltammetry (DPV). Results of the scan rate effect indicated a dual diffusion-adsorption mechanism of DAC electrooxidation that involved two electrons. A very wide concentration range, from 5 × 10−9 to 10−4 M, was detected and divided into two segments with a low detection limit of 0.387 nM in 0.1 M phosphate buffer solution/pH 2.6. The electroactivity of the developed sensor toward DAC, sensitivity, reproducibility, repeatability, robustness, and selectivity were investigated. This sensor was successfully applied for the determination of DAC in pharmaceutical and urine samples.

Urinary Tract Infections: Virus

Although viruses are common in the urinary tract in healthy people, viral infections can become a major concern in immunocompromised individuals. Patients undergoing hematopoietic stem cell or solid organ transplantation may be particularly susceptible to BK and other viruses, and experience a high risk of mortality. The most common presentation in this setting is hemorrhagic cystitis. The treatment is mostly supportive, including the reduction of immunosuppression;a variety of experimental agents has also been proposed. A different context is offered by chronic (HBV, HCV, HIV) or acute/subacute (Dengue, Hantavirus, etc.) infections, where the kidneys can be secondarily involved and suffer from several glomerular syndromes. Many protocols based on different oral direct-acting antivirals and combined antiretrovirals are available, according to the systemic infection. Viral infections can be classified according to the organ involved, i.e. lower (bladder) or upper urinary tract (kidneys, ureters), and to the mechanism of injury. A section is dedicated to the current breakout of SARS-CoV-2, which does not spare the urinary tract, sometimes with serious implications. Even if this topic is mostly the discipline of ultra-dedicated physicians, this overview has a practical approach and could be useful to a wider medical audience, especially in times of viral pandemics. © 2022 Elsevier Inc. All rights reserved.

Brain and Central Nervous System Infections: Viruses

Several viruses are neurotropic, resulting in a multitude of clinical presentations, including acute or chronic meningitis, encephalitis, myelitis, polyradiculitis, and peripheral neuropathy. All segments of the nervous system, central or peripheral, can be involved in viral infections. Viruses can directly affect the nervous system, such as in meningitis and encephalitis, or indirectly (parainfectious or postinfectious) from inflammatory or immunologic reactions, such as in Guillain-Barré syndrome (GBS) or acute disseminated encephalomyelitis (ADEM). © 2022 Elsevier Inc. All rights reserved.

Public health interventions, priority populations, and the impact of COVID-19 disruptions on hepatitis C elimination among people who have injected drugs in Montreal (Canada): A modeling study.

BACKGROUND: In Montreal (Canada), high hepatitis C virus (HCV) seroincidence (21 per 100 person-years in 2017) persists among people who have injected drugs (PWID) despite relatively high testing rates and coverage of needle and syringe programs (NSP) and opioid agonist therapy (OAT). We assessed the potential of interventions to achieve HCV elimination (80% incidence reduction and 65% reduction in HCV-related mortality between 2015 and 2030) in the context of COVID-19 disruptions among all PWID and PWID living with HIV. METHODS: Using a dynamic model of HCV-HIV co-transmission, we simulated increases in NSP (from 82% to 95%) and OAT (from 33% to 40%) coverage, HCV testing (every 6 months), or treatment rate (100 per 100 person-years) starting in 2022 among all PWID and PWID living with HIV. We also modeled treatment scale-up among active PWID only (i.e., people who report injecting in the past six months). We reduced intervention levels in 2020-2021 due to COVID-19-related disruptions. Outcomes included HCV incidence, prevalence, and mortality, and proportions of averted chronic HCV infections and deaths. RESULTS: COVID-19-related disruptions could have caused temporary rebounds in HCV transmission. Further increasing NSP/OAT or HCV testing had little impact on incidence. Scaling-up treatment among all PWID achieved incidence and mortality targets among all PWID and PWID living with HIV. Focusing treatment on active PWID could achieve elimination, yet fewer projected deaths were averted (36% versus 48%). CONCLUSIONS: HCV treatment scale-up among all PWID will be required to eliminate HCV in high-incidence and prevalence settings. Achieving elimination by 2030 will entail concerted efforts to restore and enhance pre-pandemic levels of HCV prevention and care.

Investigating the correlation between COVID-19 and the progression of chronic liver disease.

INTRODUCTION: The novel coronavirus disease 2019 has thrown light on various heterogeneous afflictions of newly emerging viruses on the human body. Early reports demonstrated direct effect of novel coronavirus on the liver, but subsequently, this did not stand up to validation. The SARS-CoV-2 virus affects the liver differentially; in healthy compared to those with preexisting liver disease. AREAS COVERED: This exhaustive paper reviews the current, literature on mechanisms by which COVID-19 affects the healthy liver and those with preexisting liver disease such as alcohol-related and nonalcoholic fatty liver, autoimmune liver disease, chronic liver disease and cirrhosis, hepatocellular carcinoma, viral hepatitis, and liver transplant recipients, with special mention on drug-and herb-induced liver injury with COVID-19 therapies. Search methodology: the review (Dec. 2022 - Jan. 2023) is based on PubMed (NLM) search using the keyword 'COVID' with supplementary searches using 'fibrosis;' 'liver;' 'cirrhosis;' 'CLD;' 'NAFLD;' 'NASH;' 'hepatocellular carcinoma;' 'hepatitis;' 'fatty liver;' 'alcohol;' 'viral;' 'transplant;' and 'liver failure.' EXPERT OPINION: Direct liver tropism of SARS-CoV-2 does not cause liver damage. Adverse events following infection depend on the severity of liver disease, the severity of COVID-19, and other risk factors such as metabolic syndrome and older age. Alcohol-related liver disease independently predicts adverse outcomes.

Exosome and virus infection.

Exosomes are messengers of intercellular communication in monolayer vesicles derived from cells. It affects the pathophysiological process of the body in various diseases, such as tumors, inflammation, and infection. It has been confirmed that exosomes are similar to viruses in biogenesis, and exosome cargo is widely involved in many viruses' replication, transmission, and infection. Simultaneously, virus-associated exosomes can promote immune escape and activate the antiviral immune response of the body, which bidirectionally modulates the immune response. This review focuses on the role of exosomes in HIV, HBV, HCV, and SARS-CoV-2 infection and explores the prospects of exosome development. These insights may be translated into therapeutic measures for viral infections and reduce the disease burden.

Microorganisms in the Pathogenesis and Management of Immune Thrombocytopenia (ITP)

Immune thrombocytopenia (ITP) represents an immune-mediated condition characterized by isolated thrombocytopenia due to the production of autoantibodies directed at human thrombocytes with a subsequent decrease in the platelet count below 100, 000 platelets/mmc. Microbial pathogens have emerged as key players in the development of ITP and are frequently listed as causes in the development of secondary ITP in adults, alongside autoimmune disorders, immune deficits, blood cancers, and others. This chapter briefly reviews the role of Helicobacter pylori, HIV, HCV, HBV, and SARS-CoV-2 (the viral agent responsible for the development of COVID-19) in the pathogenesis and management of ITP. In addition, the role of the gut microbiota and post-vaccination ITP is discussed. © The Editor(s) (if applicable) and The Author(s), under exclusive license to Springer Nature Singapore Pte Ltd. 2022.

Antiviral Potential of the Genus Panax: An updated review on their effects and underlying mechanism of action.

Viral infections are known as one of the major factors causing death. Ginseng is a medicinal plant that demonstrated a wide range of antiviral potential, and saponins are the major bioactive ingredients in the genus Panax with vast therapeutic potential. Studies focusing on the antiviral activity of the genus Panax plant-derived agents (extracts and saponins) and their mechanisms were identified and summarized, including contributions mainly from January 2016 until January 2022. P. ginseng, P. notoginseng, and P. quinquefolius were included in the review as valuable medicinal herbs against infections with 14 types of viruses. Reports from 9 extracts and 12 bioactive saponins were included, with 6 types of protopanaxadiol (PPD) ginsenosides and 6 types of protopanaxatriol (PPT) ginsenosides. The mechanisms mainly involved the inhibition of viral attachment and replication, the modulation of immune response by regulating signaling pathways, including the Janus kinase (JAK)/signal transducer and activator of transcription (STAT) pathway, cystathionine γ-lyase (CSE)/hydrogen sulfide (H2S) pathway, phosphoinositide-dependent kinase-1 (PDK1)/ protein kinase B (Akt) signaling pathway, c-Jun N-terminal kinase (JNK)/activator protein-1 (AP-1) pathway, and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) pathway. This review includes detailed information about the mentioned antiviral effects of the genus Panax extracts and saponins in vitro and in vivo, and in human clinical trials, which provides a scientific basis for ginseng as an adjunctive therapeutic drug or nutraceutical.

Liver Injury Associated with COVID-19 Infection: Pathogenesis, Histopathology, Prognosis, and Treatment.

Liver injury occurs frequently as a consequence of SARS-CoV-2 infection. Direct infection of the liver leads to hepatic impairment with elevated transaminases. In addition, severe COVID-19 is characterized by cytokine release syndrome, which may initiate or exacerbate liver injury. In patients with cirrhosis, SARS-CoV-2 infection is associated with acute-on-chronic liver failure. The Middle East and North Africa (MENA) region is one of the world's regions characterized by a high prevalence of chronic liver diseases. Both parenchymal and vascular types of injury contribute to liver failure in COVID-19, with a myriad of pro-inflammatory cytokines playing a major role in perpetuating liver injury. Additionally, hypoxia and coagulopathy complicate such a condition. This review discusses the risk factors, and the underlying causes of impaired liver functions in COVID-19, with a focus on key players in the pathogenesis of liver injury. It also highlights the histopathological changes encountered in postmortem liver tissues as well as potential predictors and prognostic factors of such injury, in addition to the management strategies to ameliorate liver damage.

Telemonitoring of the Continuum of Care of Hepatitis C During the COVID-19 Pandemic in Brazil.

Introduction: To accomplish elimination of hepatitis C virus (HCV) by 2030, as proposed by the World Health Organization, the Brazilian Ministry of Health outlined the Hepatitis C Elimination Plan, which provides coverage of all critical steps in the continuum of care (CoC) of hepatitis C. As expected, the advent of COVID-19 pandemic has disrupted the CoC of hepatitis C worldwide. The Brazilian Liver Institute launched a remote patient monitoring (RPM) program to assist the general population at risk in HCV testing and to provide linkage and retention to care for HCV-positive subjects. The RPM program was also designed to relink HCV-positive patients lost to follow-up during the COVID-19 pandemic due to their limited access to the health care system. Methods: The HCV telemonitoring number was highly advertised in Brazilian media. The RPM program was conducted by dedicated health care personnel trained to follow a predefined script designed to provide awareness, ensure consistent information for educational purposes, and recruit eligible participants to be tested for HCV. Results: From August 2020 to December 2021, 3,738 subjects entered in contact with RPM. There were 26,884 interactions (mean 7.2 interactions per participant), mostly by WhatsApp (78%). Twenty out of those 221 subjects (9%) who tested were HCV positive. Those subjects altogether with 128 other patients with HCV, tested elsewhere, were followed in the HCV CoC. Up to now, 94% of them were linked to care, 24% are undergoing treatment and 8% achieved sustained virological response (SVR). Conclusions: Our preliminary results showed that HCV CoC telemonitoring was a feasible and useful strategy to follow HCV at-risk subjects through all cascade of care until SVR during the COVID-19 health care disruption. It could be used beyond the defervescence of SARS-CoV-2 pandemic to ensure linkage to care of those HCV-positive patients.

The Role of PCSK9 in Infectious Diseases.

BACKGROUND: In recent years, many aspects of the physiological role of PCSK9 have been elucidated, in particular regarding its role in lipid metabolism, cardiovascular risk but also its role in innate immunity. Increasing evidence is available on the involvement of PCSK9 in the pathogenesis of viral infections, mainly HCV, as well as in the regulation of host response to bacterial infections, mainly sepsis and septic shock. Moreover, the action of PCSK9 has been investigated as a crucial step in the pathogenesis of malaria infection and disease severity. OBJECTIVE: Aim of this paper is to review available published literature on the role of PCSK9 in a wide array of infectious diseases. CONCLUSION: Besides the ongoing investigation on PCSK9 inhibition among HIV-infected patients for the treatment of HIV- and ART-related hyperlipidemia, preclinical studies indicate how PCSK9 is involved in reducing the replication of HCV. Moreover, a protective role of PCSK9 inhibition has also been proposed against dengue and SARS-CoV-2 viral infections. Interestingly, high plasmatic PCSK9 levels have been described in patients with sepsis. Finally, a loss of function in the PCSK9-encoding gene has been reported to possibly reduce mortality in malaria infection.

Anti-viral activity of thiazole derivatives: an updated patent review.

INTRODUCTION: Several viral infections cause life-threatening consequences in humans, making them the most serious public health concerns. Despite the fact that several antiviral medicines are available on the market, there is no full treatment for many important viral infections. To date, antiviral medicines have significantly reduced the spread of epidemics, but their continued use has resulted in the creation of drug-resistant variants throughout time. As a result, the development of new, safe, and efficient antiviral drugs is critical. AREAS COVERED: This review covered reports in the patent literature in the period 2014 to the first quarter of 2021 on the antiviral activities of thiazole derivatives. These molecules were reported to inhibit a wide range of viruses including influenza viruses, coronaviruses, herpes viruses, hepatitis B and C, bovine viral diarrhea virus, chikungunya virus and human immunodeficiency viruses. EXPERT OPINION: The most bioactive molecules can be used as lead structures for the development of new thiazole compounds with potent and selective antiviral activity. In addition, more efforts are needed to better understand the host-virus interactions for the discovery and development of new therapeutic agents and creative treatment strategies that are supposed to improve rates of clinical cure of the serious viruses.

Profile of Newly Diagnosed Patients with HIV Infection in North-Eastern Romania.

Background and Objectives: Human immunodeficiency virus infection and the acquired immunodeficiency syndrome (HIV/AIDS) pandemic are unquestionably the most serious public crisis of our time. Identifying, preventing, and treating HIV-associated comorbidities remains a challenge that must be addressed even in the era of antiretroviral therapy. Materials and Methods: In this study, we aimed to characterize the aspects of newly diagnosed patients with HIV/AIDS, during 2021-2022 in Northeastern Romania. We reviewed the frequency and associated comorbidities of these patients in correspondence with national and global results. Results: Our study found that of all newly diagnosed HIV cases (167 cases-74 cases in 2021 and 98 cases in 2022), 49.70% were diagnosed with HIV infection and 50.30% had AIDS. Based on sex correlated with the CD4+ T-lymphocyte level, the most affected were males, with a lower CD4+ T-lymphocyte level overall. The average HIV viral load was 944,689.55 copies/mL. Half of males had an abnormal ALT or AST (39.53% and 49.61%); as for the females, less than a quarter had an increased value of ALT or AST, respectively (18% and 26%). The most frequent co-infections were as follows: oral candidiasis (34.73% of patients), hepatitis B (17.37% of patients), and SARS-CoV-2 infection (8.38%), followed by hepatitis C (6.39%), tuberculosis (TB), syphilis, toxoplasmosis, Cryptococcus, Cytomegalovirus infections. Males were more affected than females, with a higher percentage of co-infections. The prescribed antiretroviral treatment focused on a single-pill regimen (79.04%) to ensure adherence, effectiveness, and safety. Therefore, 20.96% had been prescribed a regimen according to their comorbidities. Conclusions: Our study found a concerning rise in the incidence of HIV in 2022 compared to that in 2021 in Northeastern Romania, because of the rise in post-SARS-CoV-2 pandemic addressability. Advanced immunodeficiency and the burden of opportunistic infections characterize newly diagnosed HIV patients. The physicians should keep in mind that these patients may have more than one clinical condition at presentation.

Impact of COVID-19 Pandemic on Seroprevalence of HIV, HBV, HCV and HTLV I-II in a Blood Bank in Medellín, Colombia, 2019-2022.

The objective of this research was to analyze the impact of the COVID-19 pandemic on seroprevalence of HIV, HBV, HCV and HTLV I-II in donors from a blood bank in Medellin, Colombia, 2019-2022. A cross-sectional analytical study was carried out with three groups: pre-pandemic with 14,879 donors; preventive isolation with 9035; and selective isolation + new normality with 26,647 subjects. Comparisons were made with Chi2 and Bonferroni adjustment, Kruskal-Wallis' H with Dunnett's post-hoc, prevalence ratios, and multivariate logistic regression. COVID-19 decreased donations of men, altruistic and repetitive donors, and increased the age of donors. HIV increased with the COVID-19 pandemic, while HBV, HCV, and HTLV I-II decreased. The pandemic had an independent effect on these viral infections. These findings constitute an alert about what may be happening in the general population and show the importance of improving epidemiological surveillance and the investigation of these infections.

Clinician barriers, perceptions, and practices in treating patients with hepatitis C virus and substance use disorder in the United States.

The likelihood of clinicians prescribing direct-acting antiviral (DAA) therapy for patients with chronic hepatitis C virus (HCV) and substance use disorder (SUD) was assessed via a survey emailed throughout the United States to clinicians (physicians and advanced practice providers) in gastroenterology, hepatology, and infectious disease specialties. Clinicians' perceived barriers and preparedness and actions associated with current and future DAA prescribing practices of HCV-infected patients with SUD were assessed. Of 846 clinicians presumably receiving the survey, 96 completed and returned it. Exploratory factor analyses of perceived barriers indicated a highly reliable (Cronbach alpha = 0.89) model with five factors: HCV stigma and knowledge, prior authorization requirements, and patient- clinician-, and system-related barriers. In multivariable analyses, after controlling for covariates, patient-related barriers (P < 0.01) and prior authorization requirements (P < 0.01) were negatively associated with the likelihood of prescribing DAAs. Exploratory factor analyses of clinician preparedness and actions indicated a highly reliable (Cronbach alpha = 0.75) model with three factors: beliefs and comfort level; action; and perceived limitations. Clinician beliefs and comfort levels were negatively associated with the likelihood of prescribing DAAs (P = 0.01). Composite scores of barriers (P < 0.01) and clinician preparedness and actions (P < 0.05) were also negatively associated with the intent to prescribe DAAs. Conclusion: These findings underscore the importance of addressing patient-related barriers and prior authorization requirements-significant problematic barriers-and improving clinicians' beliefs (e.g., medication-assisted therapy should be prescribed before DAAs) and comfort levels for treating patients with HCV and SUD to enhance treatment access for patients with both HCV and SUD.