Antiviral Therapy最新文献

{"title":"Kidney function parameters in South African children living with HIV on antiretroviral therapy.","authors":"Yanhan Shen, Elliott Y Huang, Olivia Yin, Stephanie Shiau, Renate Strehlau, Faeezah Patel, Louise Kuhn, Fangming Lin, Stephen M Arpadi","doi":"10.1177/13596535261490958","DOIUrl":"10.1177/13596535261490958","url":null,"abstract":"<p><p>BackgroundWe evaluated longitudinal kidney function in children with perinatally acquired HIV (CWH) compared with HIV-negative controls.MethodsWe analyzed data from an observational study in Johannesburg, South Africa (2013-2018), including 220 CWH on non-tenofovir regimens and 220 controls. Baseline and follow-up visits with blood, urine, and dual-energy X-ray absorptiometry (DXA) were conducted a median of 3.7 years apart. Kidney function was assessed using serum creatinine-based (revised bedside Schwartz equation) and cystatin C-based (univariate CKiD cystatin C equation) estimated glomerular filtration rates (eGFR) and urinary microalbuminuria, proteinuria, and <math><mrow><msub><mi>β</mi><mn>2</mn></msub></mrow></math>-microglobulin. We assessed between-group differences stratified by sex. Multivariable logistic regression was utilized to identify factors associated with microalbuminuria and proteinuria.ResultsAt baseline, mean age was 6.4 years among CWH and 7.0 years among controls. At baseline, the cohort included 220 CWH and 220 controls; 49.1% of CWH and 54.6% of controls were male. Among the 190 CWH and 111 controls who completed follow-up, 48.9% of CWH and 60.3% of controls were male. CWH had lower lean mass, and higher mean creatinine- and cystatin-C based eGFR than controls. Rate of change in eGFR did not differ between CWH and controls during follow-up. An eGFR <90 mL/min/1.73 m² by cystatin C was observed in 13.3% male CWH vs 25.8% male controls (p=0.025) and 14.5% female CWH vs 25.9% female controls (p=0.049). At follow-up, proteinuria was detected in 20.7% of male CWH vs 7.5% male controls (p=0.030) and 34.4% female CWH vs 36.4% female controls (p=0.85). eGFR was >90 mL/min/1.73m² in all children with proteinuria. Female sex was associated with higher odds of microalbuminuria (aOR 5.39, 95% CI 1.26-37.25) and proteinuria (aOR 2.59, 95% CI 1.44-4.76).ConclusionsAmong early treated children with perinatally acquired HIV on non-tenofovir regimens, eGFR was higher than in HIV negative controls, while annualized eGFR change and most urine biomarkers were similar by HIV status. However, a substantial proportion of both groups had eGFR below 90 mL/min/1.73 m² and abnormal urinary markers, and male CWH had a higher prevalence of proteinuria than male controls; these findings suggest that a portion of the population have signs of abnormal kidney function that warrant further investigation and monitoring.</p>","PeriodicalId":8364,"journal":{"name":"Antiviral Therapy","volume":"31 5","pages":"13596535261490958"},"PeriodicalIF":3.3,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149068721","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Week 96 resistance analysis in participants receiving bictegravir/lenacapavir in the phase 2 ARTISTRY-1 study.","authors":"Nina Pennetzdorfer, Vidula Naik, Jairo Mauricio Montezuma-Rusca, Peter Sklar, Christian Callebaut, Nicolas A Margot","doi":"10.1177/13596535261481194","DOIUrl":"10.1177/13596535261481194","url":null,"abstract":"<p><p>BackgroundARTISTRY-1 is an ongoing Phase 2/3 study evaluating the safety and efficacy of once-daily oral bictegravir (BIC) + lenacapavir (LEN) in virologically suppressed (VS; HIV-1 RNA <50 copies/mL) participants on complex antiretroviral (ARV) regimens. Here, we report Week 96 extension-phase data after transition to BIC/LEN single-tablet regimen (STR).MethodsParticipants without known integrase strand-transfer inhibitor (INSTI) resistance were randomized (2:2:1) to BIC + LEN (75mg + 25mg or 75mg + 50mg) or stable background regimen, respectively. At the end of randomized treatment (mean of 69 weeks from baseline), participants could choose to enter the extension period and receive BIC/LEN 75/50 mg STR. Baseline resistance-associated mutations (RAMs) were evaluated from cumulative historical genotypic reports (HGRs) and Day 1 proviral DNA genotyping using a composite baseline sequence. Resistance testing was performed for confirmed virologic rebound.ResultsOf 128 randomized/dosed participants, 119 entered the extension period and received BIC/LEN STR for a median time of 96 weeks (range 11-109) from end of randomization to cutoff date. Baseline RAMs were common (nucleoside reverse transcriptase inhibitor 82%, non-nucleoside reverse transcriptase inhibitor 66%, protease inhibitor 47%; INSTI RAMs 9% (proviral DNA)). Two participants met criteria for resistance testing before resuppressing, with no treatment-emergent capsid or integrase RAMs. All 119 participants were suppressed at last observed visit.ConclusionsDurable viral suppression was maintained for up to 96 weeks in the Phase 2 extension, with all participants in the extension phase maintaining virologic suppression and no treatment-emergent resistance to study drugs, supporting long-term virologic durability of BIC/LEN STR in VS individuals on complex ART.</p>","PeriodicalId":8364,"journal":{"name":"Antiviral Therapy","volume":"31 4","pages":"13596535261481194"},"PeriodicalIF":3.3,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148787580","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"COMbination therapy with baloxavir and oseltamivir 1 for hospitalized patients with influenza: The pragmatic COMBO 1 randomized controlled trial.","authors":"Jennifer Victory, Melissa Scribani, Amanda Hasuly, Paul Jenkins, Nicole Krupa, Erik Riesenfeld, Dikshya Khatiwada, Ahmad Raja, Summia Afridi, Azkia Khan, Armando S Paez, Akram Khan, Daniel Freilich","doi":"10.1177/13596535261479944","DOIUrl":"10.1177/13596535261479944","url":null,"abstract":"<p><p>BackgroundCOMBO 1 compared time to cessation of viral shedding (TCVS) among hospitalized influenza patients treated with oseltamivir plus a single dose of baloxavir vs. oseltamivir alone.MethodsIn a quadruple-blinded, placebo-controlled parallel group multicenter randomized controlled trial, hospitalized patients with laboratory-confirmed influenza were randomly enrolled in a 1:1 ratio to Group 1 (oseltamivir+placebo) or Group 2 (oseltamivir+baloxavir). All patients were treated with oseltamivir for 5 days; one dose of baloxavir or placebo was given in identical capsules. Primary efficacy and safety outcomes were TCVS by virus titer with qCulture TCID₅₀ agglutination and 30-day severe adverse event (SAE) rate, respectively. Secondary virology, clinical, and safety outcomes were assessed. Continuous and categorical data were analyzed with Wilcoxon Rank-Sum and Fisher's Exact Tests, respectively.Results14 participants were randomized and received study drug (Group 1: n=6, Group 2: n=8); the study was stopped early due to slow accrual. Baseline characteristics were balanced. Median TCVS with qCulture was 53.3 hours in Group 1 and 25.3 hours in Group 2 (p=0.13). 30-day overall SAE rates were 16.7% and 12.5%, respectively. All patients achieved negative qCulture. Median TCVS with quantitative PCR (RT-qPCR) was 115.6 and 34.4 hours (p=0.24); % achieving viral negative by RT-qPCR was 33.3% and 75.0% (p=0.28), respectively.ConclusionsCombination therapy with oseltamivir and a single dose of baloxavir was inconclusive with non-significant trends towards shorter median TCVS vs. monotherapy with oseltamivir in hospitalized patients with influenza. Interpretation is limited by small sample size and early termination.</p>","PeriodicalId":8364,"journal":{"name":"Antiviral Therapy","volume":"31 4","pages":"13596535261479944"},"PeriodicalIF":3.3,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148808196","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Safety and efficacy of deltoid intramuscular long-acting cabotegravir and rilpivirine, a case series.","authors":"Chloé Pannecoucke, Nadia Valin, Gilles Peytavin, Sidonie Lambert, Laurence Morand Joubert, Djeneba Fofana, Estelle Nerozzi Banfi, Emma Torres, Jean-Luc Meynard, Yasmine Abi Aad, Thibault Chiarabini, Karine Lacombe","doi":"10.1177/13596535261436877","DOIUrl":"10.1177/13596535261436877","url":null,"abstract":"<p><p>ObjectiveThe objective was to evaluate the safety, pharmacokinetics and efficacy of an alternative deltoid site for CAR-LA.DesignThis is a prospective cohort of people living with HIV (PLWHIV) switching for intramuscular long acting cabotegravir and rilpivirine (CAR-LA).MethodsClinical and biological data were collected at baseline, month 1 (M1), month 3 (M3), and every three months thereafter, when available.ResultsA total of 15 patients were enrolled between August 2022 and October 2024. Of these, 11 were transgender women, 1 cisgender woman, and 3 cisgender males. The median duration of plasma HIV-1-RNA (pVL) <50 copies/mL before switching to CAR-LA was 42 months. The main criterion for selecting PLWHIV was the presence of injected silicone in the gluteal region (12 out of 15 cases). Median duration of CAR-LA was 13 months. All patients maintained a pVL<50 copies/mL at M1 and M3. No virological failure was observed in the 13 patients who were followed up to M12. One PLWHIV discontinued deltoid injections due to low plasma concentrations at M2, while another discontinued due to non-adherence which led to cabotegravir resistance at M13. Three PLWHIV reported moderate pain at the injection site, with one discontinuing treatment at M12. All CAB and RPV plasma concentrations measured after deltoid CAR-LA were comparable with those obtained following gluteal CAR-LA phase 3 studies.ConclusionDeltoïd CAR-LA seems to be a reliable and well-tolerated alternative for PLWHIV with contraindications for gluteal injections.</p>","PeriodicalId":8364,"journal":{"name":"Antiviral Therapy","volume":"31 3","pages":"13596535261436877"},"PeriodicalIF":3.3,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147925920","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Factors associated with immunological non-response in HIV patients receiving antiretroviral therapy in Southeast Asia: A systematic review.","authors":"Efrida, Aziizah Yuza","doi":"10.1177/13596535261450699","DOIUrl":"10.1177/13596535261450699","url":null,"abstract":"<p><p>ObjectiveThis systematic review summarizes factors associated with immunological non-response (INR) among people with HIV on antiretroviral therapy (ART) in Southeast Asia.MethodsWe conducted a systematic search of PubMed, ScienceDirect, DOAJ, and Lens.org for studies published between 2010 and 2025. Observational studies examining immunological outcomes following ART initiation and related factors were included. Study quality was assessed using the Newcastle-Ottawa Scale, and results were synthesized using a harvest plot.ResultTen eligible studies were included in the synthesis, comprising a total of 6,988 participants with substantial heterogeneity observed across studies. Factors associated with INR included age, sex, baseline CD4 cell count, HIV RNA levels, and co-infections. Among these factors, baseline CD4 cell count at the initiation of ART emerged as the most consistently associated determinant; lower baseline CD4 levels were linked to a higher risk of INR even with virological suppression.ConclusionThis review highlights baseline immunological status at ART initiation as a key predictor of immunological non-response in Southeast Asia. These findings underscore the critical importance of early HIV diagnosis and timely initiation of ART to prevent advanced immune damage and optimize immunological recovery.</p>","PeriodicalId":8364,"journal":{"name":"Antiviral Therapy","volume":"31 3","pages":"13596535261450699"},"PeriodicalIF":3.3,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147855824","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Epidemiology and clinical management of cytomegalovirus infection in transplant recipients in Central and Eastern Europe - a physician survey.","authors":"Alicja Dębska-Ślizień, Milena Todorović Balint, Radovan Vrhovac, Aleksandar Biljić Erski, Tina Roblek","doi":"10.1177/13596535261440692","DOIUrl":"10.1177/13596535261440692","url":null,"abstract":"<p><p>BackgroundPosttransplant cytomegalovirus (PT-CMV) infection remains a challenging complication and a major cause of morbidity and mortality in transplant recipients.MethodsThis cross-sectional study surveyed physicians treating solid organ and hematopoietic stem cell transplantation recipients from Central and Eastern European countries. Physician-reported CMV infection prevalence in transplant recipients, treatment regimens, and unmet needs for managing patients with refractory with/without resistance (R+/R-) PT-CMV infection were assessed.ResultsOverall, 164 physicians completed the survey, 23.8% of whom were nephrologists. Physicians estimated that 26.4% of patients who received a transplant in the past 12 months developed PT-CMV infection, of whom 12.9% had refractory R+/R- PT-CMV infection. On average, 66.5%, 16.5%, and 4.0% of physicians' current patients with PT-CMV infection received first-, second-, and third- or later-line treatments, respectively. Physicians considered maintenance of CMV viremia clearance (94.5%), good symptom control (94.5%), and lack of renal toxicity (93.9%) as moderately-to-extremely important treatment attributes for managing PT-CMV infection. Compared with other available treatments, more physicians indicated oral valganciclovir to have a strong-to-complete association with these treatment attributes. Overall, 63.4% of physicians indicated some level of satisfaction with conventional refractory R+/R- PT-CMV treatments. However, 54.9% of physicians reported limited experience with newly approved therapies, such as maribavir. Most physicians considered limited treatment options as a major barrier for improving patient outcomes.ConclusionSurvey findings of physicians treating transplant recipients in Central and Eastern Europe suggest the need for increased awareness of newly approved therapies with better efficacy and less toxicity for refractory R+/R- PT-CMV infection.</p>","PeriodicalId":8364,"journal":{"name":"Antiviral Therapy","volume":"31 2","pages":"13596535261440692"},"PeriodicalIF":3.3,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147760487","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"It's about time: The association between abacavir and cardiovascular disease.","authors":"Jim Young, Patrick R Lawler, Erica E M Moodie, Heiner C Bucher, Marina B Klein","doi":"10.1177/13596535261438178","DOIUrl":"10.1177/13596535261438178","url":null,"abstract":"<p><p>Data from the REPRIEVE trial have been used to study the association between treatment with abacavir and cardiovascular disease in people with HIV. Past exposure to abacavir before the trial was found to be just as risky as exposure during the trial. This calls into doubt the widely accepted hypothesis that recent exposure to abacavir increases the risk of cardiovascular disease but that risk rapidly attenuates after exposure ends. The evidence for this hypothesis is weak while evidence for an alternative hypothesis has been neglected. An alternative hypothesis is that risk from exposure to abacavir is not immediate but increases as exposure cumulates, plateauing after about three years. Confusion over the likely effect of abacavir has arisen partly because overly simplistic methods have been used to model the exposure outcome relationship in observational cohort data. Better methods are available and should be used in future to avoid misdirected research effort.</p>","PeriodicalId":8364,"journal":{"name":"Antiviral Therapy","volume":"31 2","pages":"13596535261438178"},"PeriodicalIF":3.3,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147760461","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Combination antiviral and anti-CMV immunoglobulin therapy for CMV infection: A case-control study.","authors":"Biagio Pinchera, Ludovica Fusco, Vincenzo Fotticchia, Antonio Riccardo Buonomo, Emanuela Zappulo, Nicola Schiano Moriello, Ivan Gentile","doi":"10.1177/13596535261444510","DOIUrl":"10.1177/13596535261444510","url":null,"abstract":"<p><p>BackgroundIntravenous hyper-immune anti-cytomegalovirus immunoglobulins (CMV-IG) therapy are licensed for prophylaxis, yet their therapeutic value in established CMV disease remains poorly defined. We aimed to evaluate the clinical and virological impact of adjunctive CMV-IG in combination with standard antiviral therapy in immunocompromised patients with CMV disease, compared with standard antiviral therapy alone.MethodsWe performed a single-center retrospective case-control study at A.O.U. \"Federico II\" University Hospital, Naples, Italy, including consecutive immunocompromised patients with CMV disease between March 2021 and November 2024. Cases received standard antiviral therapy plus CMV-IG (100 IU kg^-1 day^-1 for three consecutive days). Controls received antivirals only.ResultsThirty-four patients were analyzed (15 cases, 19 controls). Thirty-day survival was 93% vs 95% (p=>0.9) and composite outcome (combination of 30-day mortality and clinical response) occurred in 93% vs 90% (p=>0.9) in cases and controls, respectively. Median time-to-virological response in days was achieved 4 vs 7 days (p=<0.001), as was median duration of antiviral therapy in days 12 vs 16 days (p=0.001) and hospitalization 14 vs 19 days (p=0.004) in cases and controls, respectively. Adverse-event rates were low and comparable in the 2 groups.ConclusionsIn this real-world cohort, adjunctive CMV-IG did not affect mortality, but was associated with faster virological clearance and shorter antiviral and hospital courses, without additional toxicity.</p>","PeriodicalId":8364,"journal":{"name":"Antiviral Therapy","volume":"31 1","pages":"13596535261444510"},"PeriodicalIF":3.3,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147716073","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Harnessing SuperNatural database to identify VP35 inhibitors as anti-Ebola drug candidates: A multistage <i>In silico</i> study.","authors":"Abeer A M Hasb, Gamal A H Mekhemer, Peter A Sidhom, Ahmed Rady, Yanshuo Han, Mahmoud A A Ibrahim","doi":"10.1177/13596535251405027","DOIUrl":"10.1177/13596535251405027","url":null,"abstract":"<p><p>Ebola virus is a member of the <i>Filoviridae</i> family, which causes hemorrhagic fever in primates, exhibiting a mortality rate that can reach up to 90%. The VP35 suppresses the host IFN-<i>β/α</i> production by disrupting the immune responses of the host during viral infection, making it a putative target for therapeutic intervention. Herein, the UMH SuperNatural II database was mined to identify prospective VP35 inhibitors employing advanced <i>in</i> <i>silico</i> approaches. Filtration of the UMH SuperNatural II database was first conducted based on drug-likeness features. These compounds were screened towards VP35, and those exhibiting docking scores lower than 1DK, a reference ligand, further underwent molecular dynamics simulations (MDS), followed by binding energy calculations. Upon the assessed binding energy throughout 200 ns MDS, UMHSN00005544 and UMHSN00005545 disclosed superior binding affinity against VP35 compared to 1DK, with Δ<i>G</i>_binding values of -35.5, -34.9, and -29.3 kcal/mol, respectively. Energetic and structural evaluations were conducted for the identified natural compounds in complex with VP35 over 200 ns MDS. Post-MD analyses demonstrated the significant constancy of the investigated complexes. RMSD values averaged 0.14, 0.13, and 0.12 nm for UMHSN00005544, UMHSN00005545, and 1DK bound to VP35 over 200 ns MDS, indicating stable protein-ligand conformations. Furthermore, the ADMET characteristics of the identified natural compounds were assessed, revealing favorable pharmacokinetic and non-toxicity profiles. Density functional theory computations unveiled the electronic stability and chemical reactivity of the identified natural compounds. The obtained outcomes affirmed the substantial therapeutic potential of UMHSN00005544 and UMHSN00005545 as prospective candidates for combating EBOV, thereby necessitating further experimental investigations.</p>","PeriodicalId":8364,"journal":{"name":"Antiviral Therapy","volume":"30 6","pages":"13596535251405027"},"PeriodicalIF":3.3,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145809311","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A Phase 1 study of the safety, tolerability, and pharmacokinetics of ALG-000184 (pevifoscorvir sodium), a novel Class E capsid assembly modulator, in healthy participants.","authors":"Ed Gane, Christian Schwabe, Min Wu, Tse-I Lin, Lawrence Blatt, John Fry, Sushmita Chanda, Kha Le","doi":"10.1177/13596535251392955","DOIUrl":"10.1177/13596535251392955","url":null,"abstract":"<p><p>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_0-24), rapid absorption (median t_max 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).</p>","PeriodicalId":8364,"journal":{"name":"Antiviral Therapy","volume":"30 6","pages":"13596535251392955"},"PeriodicalIF":3.3,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145562430","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}