Antiviral Therapy最新文献

{"title":"EDP-514 in healthy subjects and nucleos(t)ide reverse transcriptase inhibitor-suppressed patients with chronic hepatitis B.","authors":"Jordan J Feld,&nbsp;Eric Lawitz,&nbsp;Tuan Nguyen,&nbsp;Jacob Lalezari,&nbsp;Tarek Hassanein,&nbsp;Paul Martin,&nbsp;Steven-Huy Han,&nbsp;Douglas Dieterich,&nbsp;Jeanne-Marie Giard,&nbsp;Guy De La Rosa,&nbsp;Alaa Ahmad,&nbsp;Ed Luo,&nbsp;Annie L Conery,&nbsp;Nathalie Adda","doi":"10.1177/13596535221127848","DOIUrl":"https://doi.org/10.1177/13596535221127848","url":null,"abstract":"<p><strong>Background: </strong>Chronic hepatitis B (CHB) remains a major cause of morbidity and mortality. EDP-514 is a potent core inhibitor of hepatitis B virus (HBV) that reduces viral load reduction in HBV-infected chimeric mice. This first-in-human study evaluated the safety, tolerability, and pharmacokinetics (PK) of EDP-514 in healthy subjects and antiviral activity in patients with CHB.</p><p><strong>Methods: </strong>In Part 1, 82 subjects received placebo or EDP-514 in fed or fasted state as single ascending doses of 50-800 mg and multiple ascending doses of 200-800 mg for 14 days. In Part 2, 24 HBV DNA-suppressed, nucleos(t)ide (NUC)-treated (i.e., NUC-suppressed) CHB patients received EDP-514 200-800 mg or placebo for 28 days.</p><p><strong>Results: </strong>EDP-514 was well tolerated in healthy subjects and CHB patients with most adverse events of mild intensity. In Part 1, EDP-514 exposure increased in an approximately dose proportional manner up to 600 mg after single doses and up to 400 mg after 14-day dosing. In Part 2, EDP-514 exposure increased linearly with dose on Day 1 and Day 28, with some accumulation for Day 28 and median trough concentrations (C_trough) approximately 20-fold above the protein-adjusted 50% effective concentration (EC₅₀) for the dose range. Mean change in HBV RNA from baseline to Day 28 was -2.03, -1.67, -1.87, and -0.58 log U/mL in the 200 mg, 400 mg, 800 mg, and placebo CHB groups, respectively.</p><p><strong>Conclusions: </strong>EDP-514 was well tolerated, had a PK profile supporting once daily dosing, and reduced HBV RNA levels in NUC-suppressed CHB patients.</p>","PeriodicalId":8364,"journal":{"name":"Antiviral Therapy","volume":null,"pages":null},"PeriodicalIF":1.2,"publicationDate":"2022-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40688226","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 favipiravir-induced angioedema and urticaria in a COVID-19 patient.","authors":"Figen Ergur Ozturk,&nbsp;Ayperi Ozturk,&nbsp;Hale Ates","doi":"10.1177/13596535221146226","DOIUrl":"https://doi.org/10.1177/13596535221146226","url":null,"abstract":"<p><p>Although favipiravir is a promising drug for coronavirus disease 2019, some adverse effects, including skin lesions, have been reported. A 56-year-old female who was prescribed favipiravir by a filiation team following a positive severe acute respiratory syndrome coronavirus 2 polymerase chain reaction test presented to our hospital. After examination, favipiravir and paracetamol were prescribed. She represented to the hospital with facial swelling and itchy rashes on her forearm. Angioedema and urticaria were diagnosed. Favipiravir was discontinued. Steroid and antihistaminic therapy were administered for angioedema. To our knowledge, this is the first reported case of favipiravir-induced angioedema and urticaria in Turkey.</p>","PeriodicalId":8364,"journal":{"name":"Antiviral Therapy","volume":null,"pages":null},"PeriodicalIF":1.2,"publicationDate":"2022-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10771329","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":"Letermovir use to treat complex cytomegalovirus reactivations in two heart transplant recipients.","authors":"Aude Boignard,&nbsp;Caroline Augier,&nbsp;Mathilde Kheng,&nbsp;Olivier Epaulard,&nbsp;Raphaele Germi","doi":"10.1177/13596535221133619","DOIUrl":"https://doi.org/10.1177/13596535221133619","url":null,"abstract":"<p><p>Letermovir, an anti-cytomegalovirus (CMV) drug, is recommended as a prophylactic agent in patients at risk of CMV infection/reactivation after allogeneic hematopoietic stem cell transplant. We report the curative and pre-emptive use of letermovir in two heart transplant recipients. In one patient with ganciclovir-resistant CMV, letermovir was successfully used to treat CMV colitis. In the second patient, letermovir was used as pre-emptive therapy for CMV reactivation, but did not prevent CMV esophagitis. In both cases, letermovir was successful for secondary prophylaxis. Curative use of letermovir may be considered if resistance or major adverse effect of other antivirals therapy is suspected.</p>","PeriodicalId":8364,"journal":{"name":"Antiviral Therapy","volume":null,"pages":null},"PeriodicalIF":1.2,"publicationDate":"2022-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40696114","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":"Antiretroviral therapy adherence patterns, virological suppression, and emergence of drug resistance: A nested case-control study from Uganda and South Africa.","authors":"Anisha Tyagi,&nbsp;Yao Tong,&nbsp;Dustin J Rabideau,&nbsp;Zahra Reynolds,&nbsp;Tulio De Oliveira,&nbsp;Richard Lessells,&nbsp;Gideon Amanyire,&nbsp;Catherine Orrell,&nbsp;Stephen Asiimwe,&nbsp;Benjamin Chimukangara,&nbsp;Jennifer Giandhari,&nbsp;Sureshnee Pillay,&nbsp;Jessica E Haberer,&nbsp;Mark J Siedner","doi":"10.1177/13596535221114822","DOIUrl":"https://doi.org/10.1177/13596535221114822","url":null,"abstract":"Background Relationships between distinct antiretroviral therapy (ART) adherence patterns and risk of drug resistance are not well understood. Methods We conducted a nested case–control analysis within a longitudinal cohort study of individuals initiating efavirenz-based ART. Primary outcomes of interest, measured at 6 and 12 months after treatment initiation, were: 1) virologic suppression, 2) virologic failure with resistance, and 3) virologic failure without resistance. Our primary exposure of interest was ART adherence, measured over the 6 months before each visit with electronic pill monitors, and categorized in three ways: 1) 6 months average adherence; 2) running adherence, defined as the proportion of days with average adherence over 9 days of less than or equal to 10%, 20%, and 30%; and 3) number of 3-, 7-, and 28-day treatment gaps in the prior 6 months Results We analyzed data from 166 individuals (107 had virologic failure during observation and 59 had virologic suppression at 6 and 12 months). Average adherence was higher among those with virologic suppression (median 83%, IQR 58–96%) versus those with virologic failure with resistance (median 35%, IQR 20–77%, pairwise P < 0.01) and those with virologic failure without resistance (median 21%, IQR 2–54%, pairwise P < 0.01). Although treatment gaps generally predicted virologic failure (P < 0.01), they did not differentiate failure with and without drug resistance (P > 0.6). Conclusions Average adherence patterns, but not the assessed frequency of treatment gaps, differentiated failure with versus without drug resistance among individuals initiating efavirenz-based ART. Future work should explore adherence-resistance relationships for integrase inhibitor-based regimens.","PeriodicalId":8364,"journal":{"name":"Antiviral Therapy","volume":null,"pages":null},"PeriodicalIF":1.2,"publicationDate":"2022-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40574836","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":"Antiretroviral therapy achieved metabolic complete remission of hepatic AIDS related Epstein-Barr virus-associated smooth muscle tumor.","authors":"Takahide Ara,&nbsp;Tomoyuki Endo,&nbsp;Hideki Goto,&nbsp;Kohei Kasahara,&nbsp;Yuta Hasegawa,&nbsp;Shota Yokoyama,&nbsp;Souichi Shiratori,&nbsp;Masao Nakagawa,&nbsp;Ken Kuwahara,&nbsp;Emi Takakuwa,&nbsp;Satoshi Hashino,&nbsp;Takanori Teshima","doi":"10.1177/13596535221126828","DOIUrl":"https://doi.org/10.1177/13596535221126828","url":null,"abstract":"<p><p>Epstein-Barr virus-associated smooth muscle tumor (EBV-SMT) is a rare mesenchymal tumor which occurs in immunocompromised patients. The immune status is an important factor in the treatment of EBV-SMTs, but the efficacy of antiretroviral therapy (ART) is not elucidated in acquired immune deficiency syndrome (AIDS) related EBV-SMTs. Here, we report the first successful case of a 29-year-old man with hepatic AIDS related EBV-SMT treated with ART solely. Positron emission tomography scan was useful for the evaluation of disease status. Recent advances in ART that enables to restore patient's immune status rapidly may change the treatment strategy in AIDS related EBV-SMT.</p>","PeriodicalId":8364,"journal":{"name":"Antiviral Therapy","volume":null,"pages":null},"PeriodicalIF":1.2,"publicationDate":"2022-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40364201","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":"Preface: Special Collection Commemorating John C. Martin.","authors":"Stephen Locarnini, Douglas Richman, Richard Whitley","doi":"10.1177/13596535221123613","DOIUrl":"10.1177/13596535221123613","url":null,"abstract":"","PeriodicalId":8364,"journal":{"name":"Antiviral Therapy","volume":null,"pages":null},"PeriodicalIF":1.2,"publicationDate":"2022-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40655784","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 randomized study of GSK3732394, an investigational long-acting biologic treatment regimen for HIV-1 infection.","authors":"Mark Krystal,&nbsp;Shiven Chabria,&nbsp;Daren Austin,&nbsp;Allen Wolstenholme,&nbsp;David Wensel,&nbsp;Max Lataillade,&nbsp;Judah Abberbock,&nbsp;Mark Baker,&nbsp;Peter Ackerman","doi":"10.1177/13596535221131164","DOIUrl":"https://doi.org/10.1177/13596535221131164","url":null,"abstract":"<p><strong>Background: </strong>The GSK3732394 multivalent protein was developed as a novel, long-acting, antiretroviral biologic treatment regimen with three independent, non-cross-resistant mechanisms for inhibiting HIV-1 entry.</p><p><strong>Methods: </strong>A single-centre, Phase 1, double-blind, randomized, placebo-controlled study was conducted in healthy volunteers, using a 2-part adaptive study design: in Part 1, participants were randomized to receive subcutaneous injection of GSK3732394 or placebo (3:1) as single ascending doses (10-mg starting dose); in Part 2, participants were intended to receive multiple ascending doses. Primary and secondary objectives included safety, pharmacokinetics (PK) and pharmacodynamics (PD; cluster of differentiation four receptor occupancy [CD4 RO]) of GSK3732394 in healthy adults; PK/PD results in healthy volunteers were used to project HIV-1 treatment success.</p><p><strong>Results: </strong>The most frequently reported adverse event was injection site reactions (ISRs; 8/18 [44%]). Most ISRs were mild (Grade 1-2; <i>n</i> = 7); one participant experienced a Grade 3 ISR (erythema ≥10 cm). All ISRs were delayed in onset (after Day 10). GSK3732394 demonstrated linear PK across all cohorts. Clearance was faster than expected, and PK/PD results were lower than expected, with the maximum dose investigated (80 mg) achieving mean trough CD4 RO of ∼25% on Day 7. The study was terminated as the PK/PD model linking PK and CD4 RO indicated that the maximum planned doses would not achieve the desired therapeutic profile.</p><p><strong>Conclusions: </strong>This study demonstrated successful deployment of PK/PD dose relationships in the design and conduct of clinical trials by leveraging the findings toward predicting probability of success, resulting in appropriate early termination (ClinicalTrials.gov, NCT03984812).</p>","PeriodicalId":8364,"journal":{"name":"Antiviral Therapy","volume":null,"pages":null},"PeriodicalIF":1.2,"publicationDate":"2022-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40394477","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":"Progress in the quality of care for newly diagnosed people with HIV in Spain (2004-2019).","authors":"Belén Alejos,&nbsp;Cristina Díez,&nbsp;María J Galindo,&nbsp;Juan C López,&nbsp;Estela Moreno-García,&nbsp;Vicente Estrada,&nbsp;Eva Poveda,&nbsp;Mohamed Omar,&nbsp;Inmaculada Jarrín,&nbsp;Juan Berenguer","doi":"10.1177/13596535221112729","DOIUrl":"https://doi.org/10.1177/13596535221112729","url":null,"abstract":"<p><strong>Background: </strong>We monitored the quality of care for newly diagnosed people with HIV (PWH) in Spain, including linkage to care within 1 month of HIV diagnosis (LC-1Mo) and viral suppression within 3 months of HIV diagnosis (VS-3Mo).</p><p><strong>Methods: </strong>Longitudinal study based on The Cohort of the Spanish AIDS Research Network (CoRIS). We used logistic regression stratified by year of HIV diagnosis (2004-2013 and 2014-2019) to assess differences by sex, country of origin, HIV risk group, age, prior AIDS, HIV Viral Load, and CD4 cell count.</p><p><strong>Results: </strong>The final analysis included 13,632 PWH: males 85%, men having sex with men (MSM) 61%, median age 35 years. LC-1Mo increased from 42% (95% CI, 38%-46%) in 2004 to 80% (95% CI, 77%-83%) in 2019 (<i>P</i> < 0.001). Median CD4⁺ cell counts at ART initiation increased from <250/mm3 in 2004-2005 to >350/mm3 since 2012 (<i>P</i> < 0.001). The percentage of initial regimens based on integrase strand transfer inhibitors (INSTI) increased from 3% in 2004 to >70% from 2016 onwards (<i>P</i> < 0.001). VS-3Mo increased from 6% (95% CI, 4%-8%) in 2004 to 45% (95% CI, 41%-49%) in 2019 (<i>P</i> < 0.001). Worst results for LC-1Mo were found among PWH acquiring HIV by injection drug use and those born in Latin American Countries across all the study period.</p><p><strong>Conclusion: </strong>Care indicators have improved among newly diagnosed PWH in Spain over the last 15 years. Removal of CD4 cell counts limitations, and probably the increasing use of INSTI-based regimens was decisive for the progress made.</p>","PeriodicalId":8364,"journal":{"name":"Antiviral Therapy","volume":null,"pages":null},"PeriodicalIF":1.2,"publicationDate":"2022-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40581891","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":"Pharmacokinetic interaction between raltegravir and rifampicin in an infant with HIV exposed to active TB: a case report.","authors":"Marlotte Aa van der Veer,&nbsp;Tom G Jacobs,&nbsp;Laura H Bukkems,&nbsp;Angela Ph Colbers,&nbsp;David M Burger,&nbsp;Henriette J Scherpbier,&nbsp;Yuma A Bijleveld","doi":"10.1177/13596535221119932","DOIUrl":"https://doi.org/10.1177/13596535221119932","url":null,"abstract":"<p><p>We report a case of an infant with HIV receiving raltegravir granules for oral suspension and rifampicin-based TB prophylaxis. Raltegravir trough levels remained subtherapeutic and viral load increased during concurrent rifampicin therapy despite using double-dosed raltegravir. Even after rifampicin therapy, a higher dose was needed. This highlights the importance of therapeutic drug monitoring and dose adjustments of raltegravir in infants with rifampicin as comedication.</p>","PeriodicalId":8364,"journal":{"name":"Antiviral Therapy","volume":null,"pages":null},"PeriodicalIF":1.2,"publicationDate":"2022-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40348306","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":"Resistance levels to non-nucleoside reverse transcriptase inhibitors among pregnant women with recent HIV infection in Malawi.","authors":"George Bello,&nbsp;Matthew Kagoli,&nbsp;Sikhona Chipeta,&nbsp;Andrew Auld,&nbsp;Joy C-W Chang,&nbsp;Joshua R DeVos,&nbsp;Evelyn Kim,&nbsp;Jonathan Mkungudza,&nbsp;Danielle Payne,&nbsp;Michael Eliya,&nbsp;Rose Nyirenda,&nbsp;Andreas Jahn,&nbsp;Taziona Mzumara,&nbsp;Bernard Mvula,&nbsp;Sufia Dadabhai,&nbsp;Ireen Namakhoma,&nbsp;Yusuf Babaye,&nbsp;Amalia Giron,&nbsp;Michael R Jordan,&nbsp;Silvia Bertagnolio,&nbsp;Gabrielle O'Malley,&nbsp;Nellie Wadonda-Kabondo","doi":"10.1177/13596535221121225","DOIUrl":"https://doi.org/10.1177/13596535221121225","url":null,"abstract":"<p><strong>Background: </strong>Information on HIV drug resistance (HIVDR) prevalence in people newly diagnosed with HIV is limited. We implemented a cross-sectional study to estimate HIVDR prevalence among pregnant women recently infected with HIV in Malawi.</p><p><strong>Methods: </strong>The HIVDR study was nested within a routine antenatal clinic (ANC) sentinel surveillance survey. Dried blood spot samples were tested for recent infection using a limiting antigen antibody assay together with HIV viral load testing. HIV-1 protease and reverse transcriptase were sequenced using Sanger sequencing. Drug susceptibility was predicted using Stanford HIVdb algorithm (version 8.9). Weighted analysis was performed in Stata 15.1.</p><p><strong>Results: </strong>Of the 21,642 pregnant women enrolled in the ANC survey, 8.4% (1826/21,642) tested HIV positive. Of these, 5.0% (92/1826) had recent HIV infection, and 90.2% (83/92) were tested by PCR. The amplification and sequencing success rate was 57.8% (48/83). The prevalence of any HIVDR was 14.6% (5/45) (95% CI: 4.7-36.8%), all of which indicated HIVDR to nonnucleoside reverse transcriptase inhibitors (NNRTIs). HIVDR to nucleoside reverse transcriptase inhibitors was 7.9% (2/45) (95% CI: 1.4-34.6%). Resistance to protease inhibitors currently in use in Malawi was not observed.</p><p><strong>Conclusions: </strong>Despite the low number of cases with presumed TDR, our study hints that resistance to NNRTIs was high, above the 10% target for regimen change. Further investigation is needed to establish the exact magnitude of presumed TDR among women recently infected with HIV. These findings support the transition to an integrase inhibitor-based first-line regimen for patients initiating or on ART.</p>","PeriodicalId":8364,"journal":{"name":"Antiviral Therapy","volume":null,"pages":null},"PeriodicalIF":1.2,"publicationDate":"2022-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/7d/b9/nihms-1831821.PMC9555317.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40703638","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}