BackgroundClass E (empty) capsid assembly modulators (CAM-Es) inhibit HBV capsid assembly, pregenomic RNA encapsidation preventing formation the establishment of covalently closed circular HBV DNA (ccDNA). ALG-000184 (pevifoscorvir sodium), is a prodrug of the Class E CAM ALG-001075.MethodsALG-000184-201 was a Phase 1 randomized, double-blind, placebo-controlled study to evaluate the safety, tolerability and pharmacokinetics of ALG-000184. Healthy participants (n = 8/cohort) received oral single-ascending doses (SAD) of ALG-000184 (40, 100, 250, and 500 mg) or placebo, and multiple-ascending daily doses (MAD) (150 mg and 250 mg) or placebo for 7 days.ResultsALG-000184 was well tolerated by 48 participants who received single doses up to 500 mg and multiple daily doses up to 250 mg for 7 days. ALG-000184 was rapidly converted to the active moiety, ALG-001075. ALG-001075 had dose-proportional increase in plasma exposure, low-to-moderate variability (18%-34% CV for AUC), rapid absorption (median t 1-3.5 h), and biphasic distribution/elimination with terminal t½ 7-8 h and minimal accumulation (∼30%). A major oxidative metabolite, ALG-000302, was identified in plasma (∼17%-24% of ALG-001075). A high-fat/high-calorie meal did not significantly impact the plasma pharmacokinetics. No differences in pharmacokinetics between Asian and non-Asian participants were observed. A concentration QT analysis indicated no statistically significant change in ΔΔQTcF with plasma ALG-001075. Urinary excretion of ALG-001075 was low following single or multiple ALG-000184 doses.ConclusionsALG-000184 demonstrated good tolerability, safety and pharmacokinetic properties in healthy participants. The pharmacokinetic profile suggests that a daily dose of 100 mg or higher will provide efficacious exposures in patients with chronic HBV infection.Clinical trial numberNCT04536337 (https://clinicaltrials.gov/study/NCT04536337).

Enteroviruses can cause severe, chronic infections in patients with primary and secondary humoral immunodeficiencies. These patients may benefit from anti-enteroviral therapy. Here, we report a patient with mantle cell lymphoma treated with chemotherapy followed by autologous stem cell transplantation and rituximab maintenance therapy, who presented with echovirus 7-associated deafness and myositis leading to severe disability. She showed marked clinical improvement and enterovirus clearance from faeces and blood after treatment with intravenous immunoglobulins (IVIgs) followed by remdesivir. We demonstrated efficacy of IVIg and remdesivir against echovirus 7 using virus neutralization and cell culture assays, which supports a potential contribution to the treatment success for both therapies.

BackgroundRAY1216 is an alpha-ketoamide-based peptide inhibitor of severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) major protease (M). This study evaluated the absorption, distribution, metabolism and excretion of [C]-labelled RAY1216 by oral administration.Research design and methodsThis phase Ι study was designed to assess the pharmacokinetics, mass balance and metabolic pathways in 6 healthy Chinese adult men after a single fasting oral administration of 240 mL (containing 400 mg/100 μCi) [C] RAY1216.ResultsRAY1216 absorbed rapidly in the plasma, with a C of 1796.83 ng/mL, t of 1.42 h and t of 5.97 h. RAY1216 is mainly excreted through feces and a small amount through urine, indicating that the excretion of RAY1216 occurs through the fecal route, within 96 h after administration, the majority (>90%) of the radioactive substances were excreted 104.17% of the metabolites were identified in urine and fecal samples. The radioactive transformation pathways suggest that RAY1216 has multiple metabolic pathways, including Oxidation-dealkylation, Mono-oxidation, Hydrolysis, and Urea binding. There were no reports of death, serious adverse events (SAEs), or withdrawals related to SAEs.ConclusionThe overall recovery rate data of radioactive substances in the excreta of all 6 subjects indicate that favourable mass balance recovery. The overall safety profile is favourable, and it demonstrates promising potential in mitigating both the duration and severity of COVID-19, and the comprehensive clinical safety and therapeutic effect are significantly superior to those of similar COVID-19 treatment drugs. RAY1216 can be referred to and further verified for the Phase II and Phase III clinical trials for the treatment of COVID-19.

BackgroundHepatitis D virus (HDV) represents the most severe form of human viral hepatitis, associated with rapid progression to cirrhosis and increased liver-related mortality. Globally, an estimated 9-19 million individuals are anti-HDV positive. To ensure early detetion, current guidelines recommend screening all HBsAg-positive individuals or, at a minimum, those with defined risk factors.MethodsThis expert consensus paper updates the current landscape of HDV management. Recommendations were derived from a structured expert panel discussion, incorporating recent evidence and clinical guideline developments, with a focus on screening, diagnosis, and antiviral therapy.ResultsThe panel emphasized the importance of systematic HDV screening in HBsAg-positive individuals. Therapeutic strategies aim at sustained HDV-RNA suppression and, ideally, HBV surface antigens (HBsAg) loss. Bulevirtide was recommended as a long-term monotherapy. Pegylated interferon alpha (PEG-IFNα), if used, should be limited to 48 weeks and tailored based on viral response and tolerability. Combination therapy with bulevirtide and PEG-IFNα may be considered in selected cases.ConclusionThis consensus provides updated recommendations for the screening, diagnosis, and treatment of HDV infection, highlighting the role of bulevirtide and individualized therapeutic approaches. As the treatment landscape continues to evolve, combination regimens and novel agents currently under investigation may offer additional options in the near future.

BackgroundPorcine reproductive and respiratory syndrome virus (PRRSV) is a pathogen that affects swine and causes substantial economic losses in the global pig industry. Despite the availability of vaccines, it remains crucial to explore innovative therapeutic strategies to control PRRSV infections. Magnolol, a bioactive compound extracted from the root and bark of , has demonstrated broad-spectrum antiviral activity in previous studies.MethodsThe cytotoxicity of magnolol was determined by the CCK-8 method. RT-qPCR, western blot, and immunofluorescence were used to study the inhibitory effect of magnolol on PRRSV N gene and protein expression through antiviral assay and viral attachment, internalization, replication and release assays. The effect of magnolol on immune-related gene expression was analysed by RT-qPCR.ResultsWe found magnolol hinders multiple facets of the PRRSV lifecycle, encompassing the stages of viral attachment and replication. Furthermore, magnolol enhances the expression of pivotal cytokines, including interleukin-6 (IL-6), interleukin-8 (IL-8), and tumour necrosis factor-α (TNF-α), during PRRSV infection, thereby reinforcing the host cells' capacity to mount an effective antiviral defence. Additionally, it exerts inhibitory effects on PRRSV replication by upregulating the expression of a disintegrin and metalloprotease 17 (ADAM17) at both the protein and mRNA levels.ConclusionsIn this study, we provide evidence demonstrating the potent efficacy of magnolol in inhibiting PRRSV replication within Marc-145 cells. Our findings underscore the potential of magnolol as a novel antiviral agent for the PRRSV control.

BackgroundDrug-resistant Mycobacterium tuberculosis strains have challenged efforts to combat tuberculosis (TB), a major global killer. C-reactive protein (CRP) shows promise as a biomarker for TB screening, particularly in HIV-positive cases, with demonstrated sensitivity and specificity in meta-analyses.MethodsWe performed a meta-analysis to assess the accuracy of CRP for screening HIV-associated PTB in outpatients, combining the sensitivities and specificities of diagnostic tests. PubMed, Web of Science, and SCOPUS were searched for articles that were published until April 2024. Quality assessment was done using the QUADAS-2 scale, and analysis was conducted using the random-effect model in STATA 17.ResultsEighteen studies, primarily from Africa (2013-2023), were analysed from an initial pool of 1186. These studies included 5625 HIV patients, 1248 of whom had PTB coinfection. Using a CRP threshold of 10 mg/L, 17 studies (5109 patients) showed 84% sensitivity (95% CI: 72%-91%) and 67% specificity (95% CI: 52%-79%) with I = 84.91%. At 8 mg/L, nine studies (3631 patients) reported 77% sensitivity (95% CI: 65%-86%) and 81% specificity (95% CI: 69%-89%) with I = 86.75%.ConclusionsOur study showed that CRP may aid in screening for PTB in PLHIV but requires clinical assessment and additional tests. Its high sensitivity can rule out PTB, but low specificity necessitates further investigation.

BackgroundThis study aims to evaluate the cost-effectiveness of tenofovir alafenamide fumarate (TAF) versus tenofovir disoproxil fumarate (TDF) for chronic hepatitis B treatment from a payer's perspective in a limited-income context like Vietnam.MethodsA Markov model was developed to estimate the lifetime cost and effectiveness (measured in quality-adjusted life year, QALY) of TAF compared to TDF in the HbeAg+ patient population. Efficacy data came from clinical trials, and costs were based on 2023 data from an exit survey of 94 inpatients and 464 outpatients in Bach Mai hospital. Other clinical data were also sourced from CHB patients at Bach Mai hospital. Along with deterministic analysis, two-way sensitivity analysis, probabilistic sensitivity analysis, threshold, and budget impact analysis were performed.ResultsCompared to TDF, TAF yielded an additional cost of USD 3,983 and an additional QALY gained of 0.14, resulting in the incremental cost-effectiveness ratio (ICER) of USD 32,090 per QALY gained. The ICER exceeds the cost-effective threshold of three-time gross domestic product (GDP) per capita, that is, USD 11,348, by 2.8 times. According to one-way sensitivity analysis, ICERs were driven mainly by transition probabilities and TDF/ TAF prices. TAF would be cost-effective compared to TDF at the three-time GDP per capital threshold if TAF price were reduced by 33.4%.ConclusionsTAF is not cost-effective compared to TDF for treating chronic hepatitis B in HBeAg+ patients. The study offers relevant evidence for policymakers to consider including TAF in the social health insurance package, with a focus on price negotiation. Future updates are needed as new evidence on the effectiveness and costs of treating chronic hepatitis B emerges.

ObjectiveThe bioequivalence of the simplified protease-inhibitor-based HIV-1 antiretroviral regimen darunavir/cobicistat (DRV/COBI) 600/90-mg fixed-dose combination (FDC) tablet dispersed in water was evaluated in healthy adults and swallowability in children living with HIV aged >3 years and weighing ≥15 to <25 kg, respectively.MethodsIn the bioequivalence study 32 healthy adult participants received either a single oral dose of the DRV/COBI-600/90-mg FDC tablet dispersed in water (test) or the separate formulations (DRV 100-mg/mL at a dose of 600-mg and COBI 90-mg tablet: reference) separated by ≥ 7 days of washout. In a separate acceptability study children living with HIV-1, aged ≥3 years and weighing ≥15 to <25 kg, received a single oral dose of the dispersed DRV/COBI-600/90-mg FDC tablet. Acceptability questionnaires were completed by observers, participants and caregivers.ResultsThe bioequivalence study indicated that the geometric mean ratios for DRV maximum plasma concentration and area under the concentration-time curve of the dispersed DRV/COBI-600/90-mg FDC tablet versus the separate formulations fell within the 80-125% bioequivalence limits. In the acceptability study in children, per independent observers 83% (10/12) of the children were able to swallow the dispersion completely and rated the dispersed FDC tablet as "ok" to "very easy" to swallow.ConclusionThe DRV/COBI 600/90-mg FDC tablet dispersed in water was bioequivalent to coadministration of the separate formulations and was acceptable for long-term daily use in the intended pediatric population.

ObjectiveTo explore the durability of multi-drug antiretroviral regimens in treatment-experienced PWH.DesignThis retrospective observational study including PWH who started mega-ART regimens between 1 January 2009 and 31 December 2019, selected from the ARCA cohort.MethodsTime-dependent events were analysed by Kaplan-Meier methods, while Cox regression models were used to define the predictors of mega-ART discontinuation.ResultsA total of 1,514 ART-experienced PWH were included. Over a median follow-up of 47 weeks (IQR 15-127), 1,299 (83%) mega-ART were interrupted, with an incidence of 85.62 per 100 person-years of follow-up. In the multivariable analysis, predictors of higher risk of mega-ART discontinuation were a higher number of antiretroviral drugs included in baseline regimens (aHR 1.206, CI 95% 1.016-1.431, = .032) and a higher baseline HIV RNA log (aHR 1.113, CI 95% 1.048-1.181, < .001); otherwise, shorter duration of previous ART was associated with a lower risk of discontinuation (aHR 0.982, CI 95% 0.965-0.999, = .037). When mega-ART was stopped, 299 PWH (23%) had HIV RNA levels above 50 copies/ml, 16/299 (1%) had HIV RNA levels >50 copies/ml but less than 200 copies/ml, 792 PWH (61%) had HIV RNA levels below 50 copies/ml, and 208 PWH (16%) had an undetermined HIV RNA load.ConclusionsMega-ART was characterized by limited durability and poor virological success.

ObjectivesTo determine seroprevalence, seroconversion, and mother-to-child transmission (MTCT) rates for dual and triplex infections of human immunodeficiency virus (HIV), hepatitis B virus (HBV), and hepatitis C virus (HCV) among pregnant women.MethodsA multicentre prospective cohort study was conducted in six randomly selected tertiary hospitals from six geopolitical zones of Nigeria. Consenting participants were tested at recruitment for triplex infections and followed-up till delivery. Retests were performed at delivery for those who tested negative for all three infections/positive for only one. Polymerase chain reaction was used for validation while rapid test kits were employed for initial screening.ResultsOf the 2775 participants recruited, 13 (0.47%; 95% CI: 0.25%-0.80%) and 4 (0.14%; 95% CI: 0.04%-0.37%) were seropositive for dual and triplex infections, respectively. Dual infections revealed seroprevalences of 0.22% for HIV-HBV (6/2775; 95% CI: 0.08%-0.47%), 0.14% for HIV-HCV (4/2775; 95% CI: 0.04%-0.37%), and 0.11% for HBV-HCV (3/2775; 95% CI: 0.02%-0.32%). Multivariable analysis highlighted significant associations between HIV/HBV co-infection and religion (adjusted odds ratio (aOR): 0.068, 95% CI: 0.006-0.757) and house ownership (aOR): 1.65 × 10, 95% CI: 1.60 × 10-1.70 × 10). Continuing our follow-up until delivery for 2403 initial participants, 2386 did not have dual or triplex infections at the start. Upon retesting at delivery, three of these women were seropositive for a dual infection of HIV and HBV, giving a seroconversion rate of 0.12% (95% CI: 0.03% to 0.37%). MTCT rate stood at 0% at 6-week post-delivery.ConclusionWe observed a relatively low seroprevalence and seroconversion rates for dual and triplex infections of HIV, HBV, and HCV among pregnant women in Nigeria and no MTCT.

Photodynamic therapy (PDT) is a two-stage treatment method making use of light energy and a photosensitizer in the presence of oxygen. PDT has already proved to bring good anti-inflammatory and anti-proliferative effects in the treatment of actinic keratosis, squamous cell carcinoma in situ as well as in superficial and nodular basal cell carcinoma. In PDT-treated lesions, infected or cancerous keratinocytes are effectively destroyed due to selective apoptosis and necrosis induced by a release of reactive oxygen species. PDT is distinguished by several features, most notably its non-invasiveness, selectivity for the target tissue, which causes fewer side effects and brings excellent cosmetic results. PDT is an effective option for treating viral diseases using a photosensitizer capable of selective accumulation in virus-infected cells not only within visible lesions, but also in subclinical disease areas where the virus is in latent form. This literature review presents recent reports on PDT for the treatment of viral skin infections, with a particular focus on the efficacy of this method. The viruses that most commonly cause skin diseases include the human papilloma virus (HPV), herpes simplex virus (HSV), varicella-zoster virus (VZV), molluscum contagiosum virus (MCV). PDT inhibits the proliferation of virus-infected cells, induces apoptosis, damages lesional blood vessels, regulates local immunity and controls viral loads. An additional advantage of PDT is the short healing period and little damage to the treated tissue. Furthermore, wider use of PDT may contribute to reducing the risk of developing drug resistance. The safety of PDT makes this method an effective way to treat viral skin diseases in difficult locations, as well as in children and immunocompromised patients.

COVID-19 has become the center of attention since its outbreak in December 2019. Despite the discovery of its preventive vaccine, role of healthy immune system is undebatable. Functional foods are continuously hunted as a promising option for a safe natural therapeutic treatment. This review demonstrates how functional foods can boost host immune system, promote antiviral operation, and synthesize biologically effective molecules against SARS-COV-2. For current review, online search was conducted for nature-based functional immune boosters against SARS-COV-2. Functional foods, alongside a healthy lifestyle, fortifies the human immune system and could all help to dramatically lower the cost burden of COVID-19, the suffering of the patients, and the mortality rates worldwide.

Dolutegravir 50 mg twice daily (BID) dosing is currently recommended in presence of strong inducers of drug metabolism. However, this dosing has been challenged by studies showing similar rates of viral suppression with dolutegravir once daily (QD) compared to BID dosing in presence of the strong inducer rifampicin. We report the case of a 41-year-old man with sustained virological suppression and documented therapeutic dolutegravir concentration on once daily dosing while treated with the strong inducer carbamazepine. Therapeutic drug monitoring can guide the need for twice daily dosing dolutegravir in presence of strong inducers.

Molnupiravir (MOV) is an orally bioavailable ribonucleoside with antiviral activity against all tested SARS-CoV-2 variants. We describe the demographic, clinical, and treatment characteristics of non-hospitalized Danish patients treated with MOV and their clinical outcomes following MOV initiation.

Integrase strand transfer inhibitors (INSTIs) have been associated with excess weight gain in people living with HIV compared to other antiretroviral agents. The mechanisms that underlie these effects are not well defined. Thus, we aimed to examine the effects of switching to INSTI-containing regimens on clinical metabolic parameters.

Nirmatrelvir has been shown to reduce morbidity and mortality associated with COVID-19. However, it is underutilized due to concerns regarding COVID-19 symptom rebound following nirmatrelvir's standard 5-day course. This study aims to identify and evaluate a nirmatrelvir dosage regimen that lowers symptom rebound.

The COVID-19 pandemic has created an urgent need for effective therapeutic agents. The SARS-CoV-2 Main Protease (M) plays a crucial role in viral replication and immune evasion, making it a key target for drug development. While several studies have explored M inhibition, identifying FDA-approved drugs with potential efficacy remains a critical research focus.

BIC/FTC/TAF showed efficacy and tolerability in randomized trials as a switch strategy in virologically-suppressed people living with HIV. We evaluated its effectiveness in a real-life setting.

Tenofovir amibufenamide (TMF) employs innovative ProTide technology and a methylation strategy to enhance the lipid solubility and plasma stability of the amide bond, providing advantages over tenofovir alafenamide (TAF). Despite promising Phase III clinical trial results demonstrating its antiviral efficacy, real-world data on TMF remains scarce. This study evaluates the antiviral efficacy and safety of TMF compared to TAF as the initial treatment in patients with high viral loads of chronic hepatitis B (CHB).

This in vitro study aimed to investigate the effect of several phenolic compounds, including doxorubicin, quercetin, and resveratrol, on HSV-1 infection.

This study aimed to analyze the risk factors for varicella encephalitis in children and establish a predictive model.