Search Results (33)

Background/Objectives: Monkeypox is endemic to the African continent and has recently garnered global attention due to reported outbreaks in non-endemic nations. No approved drug is available for non-severe cases, and some isolates gained resistance to approved antivirals. In this study, we employed a drug repositioning strategy to evaluate the efficacy of existing FDA-approved antiviral drugs if repurposed for use against emerging Monkeypox, representing a cost-effective method for identifying novel therapeutic interventions. Methods: Methodology including Egyptian virus strain isolation, propagation and titration followed by in vitro studies, molecular docking and molecular dynamics simulations combined with binding free energy were carried out. Twenty-three FDA-approved drugs, including Abacavir, Acyclovir, Amantadine, Chloroquine, Daclatasvir, Dolutegravir, Entecavir, Favipiravir, Hydroxychloroquine, Lamivudine, Molnupiravir, Nevirapine, Oseltamivir, Penciclovir, Remdesivir, Ribavirin, Sofosbuvir, Tenofovir, Valaciclovir, Valganciclovir, Velpatasvir, Zanamivir, and Zidovudine, were screened for potential anti-monkeypox activity in vitro. In silico studies were carried out against three monkeypox proteins, Thymidylate Kinase, A42R Profilin-Like Protein, and VACV D13, to identify their potential targets. Results: In vitro testing showed that two antiviral drugs are positive. The employed computational methods indicate that remdesivir demonstrated superior binding patterns with elevated scores and stable complexes throughout the simulation. Conclusions: Our findings showed that Remdesivir therapeutic compound is potent against the tested strain of MPXV, and exhibited a robust binding affinity for Thymidylate Kinase, A42R Profilin-Like Protein, and VACV D13 enzymes, and thus may potentially be utilized as antiviral for the treatment of monkeypox virus. Full article

Pangenotypic direct-acting antivirals (pDAAs) have transformed hepatitis C virus (HCV) treatment. In Italy, sofosbuvir/velpatasvir (SOF/VEL) and glecaprevir/pibrentasvir (GLE/PIB) are available. While both show similar efficacy, differences in patient profiles and potential drug–drug interactions (DDIs) may influence treatment choice. This study examined factors affecting pDAA selection and potential prescribing gaps. Using administrative databases (2018–2023) covering 3.7 million citizens, HCV patients were divided into SOF/VEL and GLE/PIB cohorts and compared by demographic, clinical, and therapeutic data. Among 5565 patients, 2837 (51%) received SOF/VEL and 2728 (49%) received GLE/PIB. SOF/VEL patients were older (60.8 vs. 57.6 years, p < 0.001) and had more comorbidities: diabetes (24% vs. 17%), mental disorders (22% vs. 14%), cancer (14% vs. 9%), and cardiovascular disease (31% vs. 22%). Hospitalization rates were higher (19% vs. 13%), as were exemption codes for chronic hepatitis (58% vs. 50%) and hypertension (32% vs. 23%). Polypharmacy was more common with SOF/VEL; 25% used ≥10 non-pDAA drugs (vs. 17%), and mean medications per patient were higher (6.3 ± 5.6 vs. 4.9 ± 5.2). SOF/VEL was often used for older, frailer patients, likely due to a more favourable DDI profile. These prescribing trends highlight the importance of tailoring pDAA choice to patient comorbidity profiles, ensuring appropriate and individualized HCV treatment. Full article

Background: Pregnancy is a time when women are uniquely engaged with the healthcare system and are often motivated to participate in activities directed toward improvement of their own health and ensuring the health of their unborn child, which also provides an opportunity for healthcare interventions such as treatment for hepatitis C virus (HCV) infection. Methods: This was a multi-site, prospective, open-label, pharmacokinetic (PK) study conducted at two large maternity hospitals in Melbourne, Australia, to evaluate the safety and pharmacokinetics of antenatal sofosbuvir (SOF) and velpatasvir (VEL) treatment administered for 12 weeks during the second and third trimester. Five women were recruited and underwent detailed PK assessments across three visits. Results: Compared to historical data in non-pregnant women, SOF area under the concentration curve (AUC) and maximum concentrations (Cmax) were 60% and 49% higher in pregnancy, respectively. In contrast, exposure to the inactive metabolite of SOF, GS-331007, was 43% lower in pregnancy. Both Cmax and AUC for VEL in pregnancy were similar to values reported in historic non-pregnant women (~21% lower in pregnant women). SOF/VEL was safe and well tolerated. Conclusions: These results add to the limited published experience prescribing antivirals in pregnancy and provide further support for a larger ongoing prospective study and other efforts to support HCV treatment in pregnancy. Full article

Background: The advent of direct-acting antivirals (DAAs) has marked a significant milestone in the therapeutic landscape of hepatitis C, greatly improving treatment efficacy. A therapeutic regimen encompassing sofosbuvir (SOF), velpatasvir (VEL), and voxilaprevir (VOX) has demonstrated strong efficacy across all genotypes of the hepatitis C virus (HCV) and has recently been incorporated into the Korean healthcare system. This study aimed to evaluate the real-world efficacy and safety of these antivirals in the South Korean population. Methods: This prospective, multicenter, observational study enrolled patients with chronic HCV treated with SOF/VEL-based regimens at six hospitals between November 2022 and January 2024. DAA-naïve patients received SOF/VEL ± ribavirin for 12 weeks. Patients who had failed prior DAA therapy received SOF/VEL/VOX for 12 weeks. The primary endpoint was a sustained virological response at 12 weeks post-treatment (SVR12). Results: Among 101 patients treated with SOF/VEL, the mean age was 64.71 years, and 40.9% were male. Genotypes 1b and 2 were identified in 40.6% and 59.4% of patients, respectively. Two patients had a history of interferon-based treatment. The mean baseline HCV RNA level was 3,088,097 IU/mL. Cirrhosis was observed in 26.7% of patients (21.8% compensated; 5.0% decompensated). Of the 101 patients, 12 were lost to follow-up. Among the 89 patients who completed follow-up, SVR12 was achieved in 100.0% (89/89), including 5 patients with decompensated cirrhosis. In the SOF/VEL/VOX group, 17 patients were treated. The mean age was 61.84 years, 29.4% were male, and four had compensated cirrhosis. One patient was lost to follow-up. SVR12 was achieved in 100.0% (16/16) of the patients who completed follow-up. No serious adverse events (≥grade 3) were reported in either group during the DAA treatment period. Conclusions: In this first prospective real-world study in South Korea, SOF/VEL-based regimens demonstrated excellent efficacy and safety, achieving 100% SVR12 in the per-protocol population, including patients with cirrhosis and prior treatment failure. Full article

The combination of sofosbuvir/velpatasvir/voxilaprevir (SOF/VEL/VOX) is recommended as a salvage therapy for treatment-experienced chronic hepatitis C (CHC) patients. However, it is used in our country for treatment-naïve and treatment-experienced patients. This study aims to present real-world data from Türkiye on CHC patients treated with SOF/VEL/VOX. The present study was conducted by the Viral Hepatitis Study Group of the Turkish Society of Clinical Microbiology and Infectious Diseases (KLİMİK). It was a multicenter, retrospective, observational study. The data were collected from patients receiving SOF/VEL/VOX therapy at 12 medical centers in Türkiye between 1 June 2022 and 31 December 2024. The patients had received the treatment for 8 to 12 weeks. Of the 139 patients enrolled, 63.3% (n = 88) were male, with a mean age of 54.4 years. Most patients were non-cirrhotic (94.2%, n = 131) and treatment-naïve (92%, n = 128); 49.6% (n = 69) were infected with genotype 1b. Early virologic response (EVR) could be assessed in 126 patients, with an EVR rate of 82.5% (n = 104). End-of-treatment data were available for 113 patients, all achieving an end-of-treatment response. Among the 80 patients for whom week-12 post-treatment data were available, 97.5% sustained virologic response at week 12 (SVR12). Significant improvements were observed in AST, ALT, and platelet levels, along with reductions in APRI and FIB-4 scores (p = 0.001).” No serious adverse events leading to treatment discontinuation were reported. Mild adverse events included pruritus (2.1%, n = 3), fatigue (2.1%, n = 3), and nausea (1.4%, n = 2). The SOF/VEL/VOX combination is a highly effective and well-tolerated treatment option in treatment-naïve CHC patients, achieving an SVR12 rate of 97.5%. Full article

Background: The aim of this study was to assess the cost effectiveness of a screening and treatment intervention approach for chronic HCV infection in Zimbabwe. Methods: Using a decision tree and a validated Markov model, we estimated the lifetime costs and health effects of screening for and treating HCV infections from a healthcare perspective. We evaluated three screening strategies, namely the following: i. no screening; ii. screening among the general population; and iii. screening among high-risk groups. Incremental cost effectiveness ratios were calculated for the strategies that were not dominated. We used deterministic and probabilistic sensitivity analyses to explore the impacts of parameter uncertainty on cost effectiveness outcomes. Results: The strategy of screening among high-risk groups and treating with sofosbuvir/velpatasvir had an incremental cost of USD 1201 and incremental quality-adjusted life years (QALY) of 2.01, yielding an incremental cost effectiveness ratio (ICER) of USD 604 per QALY gained as compared to no screening. The ICER was below the 0.5 times the gross domestic product per capita parameter (USD 796), making the intervention potentially cost effective. The strategy to screen among the general population was dominated, because it costed more and resulted in fewer QALYs than its comparators. Conclusions: Screening for HCV among high-risk populations followed by treatment using sofosbuvir/velpatasvir is cost effective under the assumptions made in this study. Full article

While direct-acting antivirals (DAAs) are available for the treatment of chronic Hepatitis C virus (HCV) patients in Nepal, knowledge of the circulating genotypes/subtypes and drug target gene mutations of HCV is currently unavailable. Here, we describe HCV genotypes/subtypes and identify antiviral target gene mutations in patients at a tertiary care hospital using genome data. A cross-sectional study was conducted from December 2019 to February 2024, where PCR followed by whole genome sequencing was performed to identify HCV genotypes/subtypes and drug target gene mutations. Among all the patients who tested positive for anti-HCV, 70.6% (149/211) were HCV RNA positive, while 68.2% (30/44) were genotype/subtype 3a, followed by 1a (18.2%, 8/44) and others (13.6%, 6/44), including new subtypes 3g and 3i from Nepal. Subtype 3a was also the dominant subtype (≥70%) among intravenous drug users and sexual routes of transmission. We found 70.5% of the samples with resistant mutations in the NS3/4A region, 22.7% in NS5A, and 45.5% in NS5B. Resistant mutations against sofosbuvir, pibrentasvir, velpatasvir, daclatasvir, and dasabuvir were found at 25%, 18%, 16%, 16%, and 2%, respectively, mostly on subtype 3a. The predominant HCV genotype/subtype in our patient group was 3a, and resistance mutations against direct-acting antivirals were found in most untreated patients. Full article

Hepatitis C virus (HCV) eradication is usually associated with dyslipidemia. Most studies in this field have focused on genotype-specific direct-acting antivirals (DAAs), with research on pangenotypic DAAs being limited. This study examined how two pangenotypic DAA regimens, glecaprevir/pibrentasvir (GLE/PIB) and sofosbuvir/velpatasvir (SOF/VEL), affect lipid profiles and insulin resistance after viral eradication in chronic HCV patients. A total of 100 patients (57 with GLE/PIB and 43 with SOF/VEL) treated between September 2020 and January 2022 were included in the retrospective analysis. This study found a significant increase in LDL and TC levels after treatment (p < 0.001), but no significant changes in triglycerides, high-density lipoprotein, HbA1C, or the Homeostatic Model Assessment of Insulin Resistance. According to a logistic regression analysis, higher baseline LDL or TC and lower baseline glucose are predictors of the degree of increase in LDL or TC following a sustained virological response. Both pangenotypic DAA regimens significantly impact lipid profiles, particularly LDL and TC, but not insulin resistance. This study emphasizes the need for more research into the long-term metabolic effects of DAAs. Full article

The treatment landscape for hepatitis C virus (HCV) infection has transformed over the past few decades, evolving from the limited efficacy of interferon (IFN) monotherapy to the highly successful pan-genotypic direct-acting antivirals (DAAs) used today. Initially, alpha-interferon monotherapy, introduced in the 1990s, was the standard treatment, yet it provided low sustained virological response (SVR) rates and caused significant adverse effects, limiting its utility. The development of pegylated interferon (peg-IFN) improved the pharmacokinetic profile of IFN, allowing for less frequent dosing and modestly improved response rates. When combined with ribavirin, peg-IFN achieved higher SVR rates, especially in non-genotype 1 HCV infections, but the combination also brought additional side effects, such as anemia and depression. The advent of the first-generation DAAs, such as telaprevir and boceprevir, marked a significant milestone. Combined with peg-IFN and ribavirin, these protease inhibitors boosted response rates in patients with genotype 1 HCV. However, high rates of adverse effects and drug resistance remained challenges. Second-generation DAAs, like sofosbuvir and ledipasvir, introduced IFN-free regimens with improved safety profiles and efficacy. The most recent advances are pan-genotypic DAAs, including glecaprevir-pibrentasvir and sofosbuvir-velpatasvir, which offer high SVR rates across all genotypes, shorter treatment durations, and fewer side effects. Current pan-genotypic regimens represent a cornerstone in HCV therapy, providing an accessible and effective solution globally. Full article

Background: The advent of direct-acting antiviral (DAA) therapy has revolutionized the treatment landscape of the hepatitis C virus (HCV) infection. This study aimed to provide a comprehensive research study of the real-world effectiveness and safety of DAA treatment, representing the first study conducted in the Omani population. Methods: A cross-sectional study was conducted including 375 HCV patients with different genotypes, treated using different DAA regimens, with or without ribavirin, between January 2012 and December 2020 at the Sultan Qaboos University Hospital and the medical city for military and security services, two tertiary hospitals in Muscat, Oman. The rate of sustained virologic response 12 weeks after completing the regimen (SVR-12) was analyzed as the primary outcome. Secondary outcomes included treatment safety and adverse events related to DAA therapy, as reported by patients and treating physicians. Results: A total of 375 patients were included in the study, with a mean age of 47.3 ± 15.4 years. Most were male (59.2%) and treatment-naïve (71.7%). The prevalence of liver cirrhosis was 19.7%, while 4.0% had hepatocellular carcinoma (HCC). The SVR-12 rate among treatment-naïve and treatment-experienced patients was 95.0% and 93.4%, respectively. Several parameters were associated with DAA treatment failure, including liver cirrhosis (p = 0.004) and active HCC (p = 0.009). Following SVR-12, significant improvements were observed in alanine transaminase, bilirubin, and albumin levels, Fibrosis-4 Index, and liver stiffness measurements compared to baseline (p <0.001 each). No significant adverse effects were reported. Conclusions: Based on our real-world experience, DAAs are highly effective in treating patients with HCV infection in Oman, with an excellent tolerability and safety profile. Full article

Background: Direct oral anticoagulants (DOACs) are recommended for the management of thrombosis prophylaxis, especially in patients with atrial fibrillation. As substrates of cytochrome P450 (CYP) 3A4 and/or P-glycoprotein, they are implicated in potential drug–drug interactions. NS5A/NS5B inhibitors are direct-acting agents (DAAs) against the Hepatitis C Virus (HCV) infection that exert a mild inhibition of P-glycoprotein without effects on CYP3A4. A DOAC and NS5A/NS5B inhibitor co-administration may lead to an increased risk of bleeding. Real-world data on the concomitant use of DOACs and DAAs are scarce. On this purpose, we perform a retrospective analysis on the risk of vascular adverse events (bleeding and thrombosis) among HCV patients under DOAC/DAA therapy, even in advanced liver disease. Methods: Between May 2015 and April 2023, patients treated with sofosbuvir-based DAA regimens and DOACs were consecutively included in this study from 12 Italian medical centers. Baseline characteristics, especially concerning bleeding risk and liver function, were collected. The occurrence of bleeding events, classified as major and minor, was the primary endpoint. Secondary endpoints were the rate of any thrombotic events and/or the need for discontinuation of one or both treatments. Moreover, a cohort of patients, matched by demographic characteristics (age and sex), that switched to vitamin K antagonists (VKAs) during the antiviral treatment was compared with the DOAC/DAA group. Results: A total of 104 patients were included. Thirty-eight of them (36.5%) were cirrhotic. Atrial fibrillation was an indication for anticoagulation in almost all cases (76%). Rivaroxaban (35.6%) was the most used DOAC, followed by apixaban (26.9%), dabigatran (19.2%) and edoxaban (18.3%). Sofosbuvir/velpatasvir (78.8%) was the most prescribed DAA, and all patients were already on anticoagulant therapy before the start of DAAs. During concomitant DOAC/DAA treatment, no major bleeding events were recorded, while four minor bleeding events occurred, but none resulted in DAA or DOAC discontinuation. At univariate analysis, the only additional risk factor statistically related to bleeding events was the anticoagulant therapy (hazard ratio [HR]: 13.2, 95% confidence interval 1,6-109). Performing an evaluation by a LOGIT binomial analysis with demographic characteristics, the antiplatelet therapy remained statistically associated to bleeding events. No significant differences were found in the rate of clinically relevant bleeding when the main population was compared with the VKA-switched cohort. A single major bleeding event leading to anticoagulation and DAA discontinuation was reported in VKA-switched matched cohort. Conclusions: In our study, the concomitant use of NS5A/NS5B inhibitors with DOAC showed good safety, and the only risk factor associated with bleeding events was the concomitant antiplatelet therapy. These findings support the use of DOACs during sofosbuvir-based HCV treatment, even in advanced liver disease. Replacing DOACs with VKAs does not appear to be of clinical benefit. Full article

Direct-acting antivirals (DAAs) revolutionized the therapeutics of chronic hepatitis C. The emergence and transmission of HCV variants with resistance-associated substitutions (RASs) can undermine HCV treatment. This study aimed to assess the prevalence and temporal trends of RASs in HCV, with a particular focus on clinically relevant RASs (cr-RASs). Near-complete HCV GenBank sequences archived in the Los Alamos HCV Database were analyzed. The study period was divided into two phases: before 2011 and from 2011 onward. Identification of RASs across three DAA classes (NS3, NS5A, and NS5B inhibitors) was based on the 2020 EASL guidelines. The AASLD-IDSA recommendations were used to identify cr-RASs for three HCV genotypes/subtypes (1a, 1b, and 3) and four DAA regimens: ledipasvir/sofosbuvir; elbasvir/grazoprevir; sofosbuvir/velpatasvir; and glecaprevir/pibrentasvir. The final HCV dataset comprised 3443 sequences, and the prevalence of RASs was 50.4%, 60.2%, and 25.3% in NS3, NS5A, and NS5B, respectively. In subtype 1a, resistance to ledipasvir/sofosbuvir was 32.8%, while resistance to elbasvir/grazoprevir was 33.0%. For genotype 3, resistance to sofosbuvir/velpatasvir and glecaprevir/pibrentasvir was 4.2% and 24.9%, respectively. A significant increase in cr-RASs was observed across the two study phases as follows: for ledipasvir/sofosbuvir in subtype 1a, cr-RASs increased from 30.2% to 35.8% (p = 0.019); for elbasvir/grazoprevir in subtype 1a, cr-RASs increased from 30.4% to 36.1% (p = 0.018); In subtype 1b, neither ledipasvir/sofosbuvir nor elbasvir/grazoprevir showed any cr-RASs in the first phase, but both were present at a prevalence of 6.5% in the second phase (p < 0.001); for sofosbuvir/velpatasvir in genotype 3, cr-RASs increased from 0.9% to 5.2% (p = 0.006); and for glecaprevir/pibrentasvir, cr-RASs increased from 12.0% to 29.1% (p < 0.001). The rising prevalence of HCV RASs and cr-RASs was discernible. This highlights the necessity for ongoing surveillance and adaptation of novel therapeutics to manage HCV resistance effectively. Updating the clinical guidelines and treatment regimens is recommended to counteract the evolving HCV resistance to DAAs. Full article

Prior to the Food and Drug Administration approval of ledipaspavir/sofosbuvir (Harvoni^®) in 2014, the treatment of hepatitis C was interferon plus or minus ribavirin. This treatment had low cure rates for hepatitis C virus and was teratogenic and therefore avoided in pregnant patients. Vertical transmission is the most common transmission of hepatitis C in pediatric patients, whereas medical equipment that was not properly cleaned and sterilized, blood products which were not checked (historically), sharing and reusing syringes and needles, and dialysis are the most common forms of hepatitis C transmission in adults. The treatment of pregnant women with direct-acting antivirals is important because the treatment of pediatric patients cannot begin until three years of age and does not always occur prior to the symptom development of hepatitis C. This review article will include glecaprevir/pibrentasvir (Mayvret^®), sofosbuvir/velpatasvir (Epclusa^®), and sofosbuvir/velpatasvir plus voxilaprevir (Vosevi^®). We aim to review the teratogenic risk of direct-acting antivirals as well as currently published clinical trials and ongoing research on direct-acting antiviral hepatitis C treatment in pregnancy in this publication. Full article

Children represent only a small proportion of those infected with the hepatitis C virus (HCV) compared to adults. Nevertheless, a substantial number of children have chronic HCV infection and are at risk of complications including cirrhosis, portal hypertension, hepatic decompensation with hepatic encephalopathy, and hepatocellular carcinoma in adulthood. The overall prevalence of the HCV in children was estimated to be 0.87% worldwide. The HCV spreads through the blood. Children born to women with chronic hepatitis C should be evaluated and tested for HCV due to the known risk of infection. The course of treatment for hepatitis C depends on the type of HCV. Currently, there are two pan-genotype HCV treatments (Glecaprevir/pibrentasvir and Sofosbuvir/velpatasvir) for children. We aim to review the updated clinical guidelines on the management of HCV infection in children, including screening, diagnosis, and long-term monitoring, as well as currently published clinical trials and ongoing research on direct acting antiviral hepatitis C treatment in children. Full article

The introduction of direct-acting antiviral agents (DAAs) into clinical practice has revolutionized the therapeutic approach to patients with chronic hepatitis C virus (HCV) infection. According to the most recent guidelines, the first line of treatment for HCV infection involves the use of one of three pan-genotypic DAA combinations, sofosbuvir/velpatasvir (SOF/VEL), glecaprevir/pibrentasvir (GLE/PIB), and sofosbuvir/velpatasvir/voxilaprevir (SOF/VEL/VOX). These drugs have been shown to be effective and safe in numerous clinical trials and real-world studies, but special populations have been neglected. Among the special populations to be treated are elderly patients, whose numbers are increasing in clinical practice. The management of these patients can be challenging, in particular due to multiple comorbidities, polypharmacotherapy, and potential drug–drug interactions. This narrative review aims to summarize the current scientific evidence on the efficacy and safety of DAAs in the elderly population, both in clinical trials and in real-life settings. Although there is still a paucity of real-world data and no clinical trials have yet been conducted in the population aged ≥ 75 years old, some considerations about the efficacy and safety of DAAs in the elderly can be made based on the results of these studies. The pan-genotypic associations of DAAs appear to be as efficacious and safe in the elderly population as in the general population; this is both in terms of similar sustained virologic response (SVR) rates and similar frequencies of adverse events (AEs). However, further studies specifically involving this patient population would be necessary to confirm this evidence. Full article