Antiviral Therapy最新文献

{"title":"Clinical efficacy and safety in telbivudine- or tenofovir-treated hepatitis B e antigen-positive pregnant women.","authors":"Haohui Deng,&nbsp;Shuzhen Liang,&nbsp;Min Xu,&nbsp;Li Zhuo,&nbsp;Hongbo Gao,&nbsp;Keng Chen,&nbsp;Yuming Shi,&nbsp;Huihui Li,&nbsp;Qian Jiao,&nbsp;Liansheng Lin,&nbsp;Yan Lei,&nbsp;Huiyuan Liu","doi":"10.3851/IMP3345","DOIUrl":"https://doi.org/10.3851/IMP3345","url":null,"abstract":"<p><strong>Background: </strong>Telbivudine (LdT) and tenofovir (TDF) are widely used in pregnant women to prevent vertical transmission; however, limited data are available on the differences in clinical efficacy and safety between the two drugs.</p><p><strong>Methods: </strong>A total of 307 hepatitis B e antigen (HBeAg)-positive pregnant women with complete follow-up data were enrolled, the patients with alanine aminotransferase (ALT) levels <1×ULN at baseline were enrolled to cohort 1 for treatment from 28 ±4 weeks gestation to delivery, while ALT levels >1×ULN at baseline were enrolled to cohort 2 for treatment from 28 ±4 weeks gestation and continued after delivery. The clinical efficacy and safety was compared in LdT- and TDF-treated patients. In addition, 32 patients in cohort 1 were analysed for nucleoside analogue (NA)-related resistance mutations at baseline and after delivery.</p><p><strong>Results: </strong>The results showed that HBV DNA levels were significantly lower at delivery than at baseline (P<0.001), but the decreases in HBV DNA, ALT, total bilirubin and total bile acid levels did not differ between the LdT- and TDF-treated patients at different time points (P>0.05) in the two cohorts. However, gastrointestinal adverse effects (vomiting) occurred more frequently in TDF-treated than LdT-treated patients (6.6% versus 0.0%; P=0.001). The results of NA-related resistance mutations analysis in cohort 1 revealed that short-term LdT or TDF treatment did not significantly change the NA-related resistance mutations (P>0.05).</p><p><strong>Conclusions: </strong>This study revealed that the clinical efficacy in LdT- or TDF-treated HBeAg-positive Chinese pregnant women is similar, and gastrointestinal adverse effects occurred more frequently in TDF-treated patients.</p>","PeriodicalId":8364,"journal":{"name":"Antiviral Therapy","volume":"25 1","pages":"33-41"},"PeriodicalIF":1.2,"publicationDate":"2020-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"37636527","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":"CD4⁺:CD8⁺ T-cell ratio changes in people with HIV receiving antiretroviral treatment.","authors":"Maria J Vivancos-Gallego,&nbsp;Hajra Okhai,&nbsp;Maria J Perez-Elías,&nbsp;Cristina Gomez-Ayerbe,&nbsp;Ana Moreno-Zamora,&nbsp;Jose L Casado,&nbsp;Carmen Quereda,&nbsp;Javier Martinez Sanz,&nbsp;Matilde Sanchez-Conde,&nbsp;Sergio Serrano-Villar,&nbsp;Santos Del Campo,&nbsp;Fernando Dronda,&nbsp;Juan Carlos Galan,&nbsp;Caroline A Sabin,&nbsp;Santiago Moreno","doi":"10.3851/IMP3354","DOIUrl":"https://doi.org/10.3851/IMP3354","url":null,"abstract":"<p><strong>Background: </strong>Cofactors associated with persistently abnormal CD4⁺:CD8⁺ T-cell ratio in people with HIV (PWH) on antiretroviral treatment (ART) might change over time as the population of people with HIV ages or as new ART drugs become available. The main objective of our study was to determine the long-term associations of baseline factors, including the CD4⁺ T-cell count and ratio, with ratio normalization (≥1). In addition to this, we explored whether the ratio remained associated with the risk of both AIDS and non-AIDS events among individuals on suppressive ART.</p><p><strong>Methods: </strong>Clinic-based study in a tertiary, university hospital in Madrid. People with HIV starting a first-line ART regimen (January 2006-June 2017) were included in a prospective national multicentre cohort (CoRIS). People with controlled HIV-infection within the first year of ART initiation and complete CD4⁺ and CD8⁺ T-cell records were selected. Cox proportional hazard (PH) regression models were used to estimate the cumulative incidence of ratio normalization and to examine associations with socio-demographic and clinical variables. To investigate factors independently associated with the development of AIDS and non-AIDS events we used a time updated Poisson regression model.</p><p><strong>Results: </strong>The study included 557 subjects. During follow-up (median 5.24 years), 44% of participants achieved a ratio of 1 within a median of 1.49 years. In a multivariate PH model, pre-ART factors negatively associated with ratio normalization were the pre-ART CD4⁺:CD8⁺ T-cell ratio and mode of HIV acquisition. For the secondary analysis, 1.3 events/100 person years of follow-up were observed. After adjustment, older age, HIV RNA >200 copies/ml and CD4⁺:CD8⁺ T-cell ratios over follow-up, remained significantly associated with the development of AIDS and non-AIDS events. In contrast, pre-ART ratio was not associated with the risk of AIDS and non-AIDS events.</p><p><strong>Conclusions: </strong>In summary, our study showed that higher pre-ART CD4⁺:CD8⁺ T-cell ratio is associated with rates of ratio normalization ≥1. In addition, the risk of AIDS and non-AIDS events seems to be predicted by the time updated CD4⁺:CD8⁺ T-cell ratio not by the pre-ART CD4⁺:CD8⁺ T-cell ratio. Therefore, CD4⁺:CD8⁺ T-cell ratio should be considered as a dynamic marker for translation into clinical practice.</p>","PeriodicalId":8364,"journal":{"name":"Antiviral Therapy","volume":"25 2","pages":"91-100"},"PeriodicalIF":1.2,"publicationDate":"2020-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"37875509","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":"Survival after long-term ART exposure: findings from an Asian patient population retained in care beyond 5 years on ART.","authors":"Rimke Bijker,&nbsp;Sasisopin Kiertiburanakul,&nbsp;Nagalingeswaran Kumarasamy,&nbsp;Sanjay Pujari,&nbsp;Ly P Sun,&nbsp;Oon T Ng,&nbsp;Man P Lee,&nbsp;Jun Y Choi,&nbsp;Kinh V Nguyen,&nbsp;Yu J Chan,&nbsp;Tuti P Merati,&nbsp;Do D Cuong,&nbsp;Jeremy Ross,&nbsp;Awachana Jiamsakul","doi":"10.3851/IMP3358","DOIUrl":"https://doi.org/10.3851/IMP3358","url":null,"abstract":"<p><strong>Background: </strong>This study investigated survival in people living with HIV being followed-up from 5 and 10 years after antiretroviral therapy (ART) initiation in a multi-country Asian cohort.</p><p><strong>Methods: </strong>We included patients in follow-up >5 years after ART initiation. Factors associated with mortality beyond 5 and 10 years on ART were analysed using competing risk regression with time-updated variables.</p><p><strong>Results: </strong>Of 13,495 patients retained after 5 years on ART, 279 subsequently died (0.56/100 person-years). Increased mortality was associated with age >50 years (sub-hazard ratio [sHR] 2.24, 95% CI 1.58, 3.15, compared with ≤40 years), HIV exposure through injecting drug use (sHR 2.17, 95% CI 1.32, 3.56), HIV viral load ≥1,000 copies/ml: sHR 1.52, 95% CI 1.05, 2.21, compared with <400), regimen (second-line regimen: sHR 2.11, 95% CI 1.52, 2.94, and third-line regimen: sHR 2.82, 95% CI 2.00, 3.98, compared with first-line regimen), HBV coinfection (sHR 2.23, 95% CI 1.49, 3.33), fasting plasma glucose ≥126 mg/dl (sHR 1.98, 95% CI 1.22, 3.21, compared with <100 mg/dl) and estimated glomerular filtration rate <60 ml/min/1.73 m² (sHR 2.57, 95% CI 1.56, 4.22). Decreased mortality was associated with transmission through male-to-male sexual contact (sHR 0.44, 95% CI 0.22, 0.88, compared with heterosexual transmission) and higher CD4⁺ T-cell count (200-349 cells/µl: sHR 0.27, 95% CI 0.20, 0.38, 350-499 cells/µl: sHR 0.10, 95% CI 0.07, 0.16 and ≥500 cells/µl: sHR 0.09, 95% CI 0.06, 0.13, compared with <200 cells/µl). Results after 10 years were similar, but most associations were weaker due to limited power.</p><p><strong>Conclusions: </strong>Next to preventing ART failure, HIV programmes should carefully monitor and treat comorbidities, including hepatitis, kidney disease and diabetes, to optimize survival after long-term ART exposure.</p>","PeriodicalId":8364,"journal":{"name":"Antiviral Therapy","volume":"25 3","pages":"131-142"},"PeriodicalIF":1.2,"publicationDate":"2020-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7641962/pdf/nihms-1614215.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"37900874","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}

{"title":"Viral suppression is comparable with 0.5 mg and 1.0 mg daily doses of entecavir in treatment-naive HBV-related decompensated cirrhosis.","authors":"Amit Goel,&nbsp;Sumit Rungta,&nbsp;Prashant Verma,&nbsp;Abhai Verma,&nbsp;Ajay Narayan Verma,&nbsp;Praveer Rai,&nbsp;Rakesh Aggarwal","doi":"10.3851/IMP3375","DOIUrl":"https://doi.org/10.3851/IMP3375","url":null,"abstract":"<p><strong>Background: </strong>For patients with HBV infection who have decompensated cirrhosis (DC), a higher dose (1.0 mg/day) of entecavir is recommended than that used for those with compensated disease (0.5 mg/day), though with very little supporting data. We therefore compared the viral suppression achieved with 0.5 mg/day and 1.0 mg/day of entecavir in patients with HBV-related DC (NCT03345498).</p><p><strong>Methods: </strong>Treatment-naive patients with HBV-related DC and serum HBV DNA titre exceeding 100,000 IU/ml received either dose of entecavir for 24 weeks. HBV DNA concentration was measured in blood specimens collected at baseline and after 2, 4, 8, 12 and 24 weeks of entecavir treatment.</p><p><strong>Results: </strong>Participants in the 0.5 mg/day (n=13) and 1.0 mg/day (n=16) groups had similar baseline hepatitis B e antigen (HBeAg) positivity rates (12/13 and 12/16; P=0.34) and median (range) log₁₀ serum HBV DNA levels (6.81 [5.01-8.12] and 7.45 [5.24-8.65]; P=0.17). The two doses led to similar reductions in serum HBV DNA levels after 2, 4, 8, 12 and 24 weeks of entecavir administration. At 24 weeks, 3 of the 13 patients receiving 0.5 mg/day and 1 of the 16 patients receiving 1.0 mg/day of entecavir had undetectable serum HBV DNA. Serum albumin level showed significant and similar improvement at the end of 24 weeks in the two groups.</p><p><strong>Conclusions: </strong>Treatment-naive patients with HBV-related DC can be treated with entecavir in a 0.5 mg/day dose instead of the higher 1.0 mg/day dose, without compromising the degree of virological suppression. ClincialTrials.gov number NCT03345498.</p>","PeriodicalId":8364,"journal":{"name":"Antiviral Therapy","volume":"25 5","pages":"267-273"},"PeriodicalIF":1.2,"publicationDate":"2020-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39122127","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":"An expanded HIV care cascade: ART uptake, viral load suppression and comorbidity monitoring among adults living with HIV in Asia.","authors":"Rimke Bijker,&nbsp;Nagalingeswaran Kumarasamy,&nbsp;Sasisopin Kiertiburanakul,&nbsp;Sanjay Pujari,&nbsp;Oon Tek Ng,&nbsp;Ly Pehn Sun,&nbsp;Tuti Parwati Merati,&nbsp;Kinh Van Nguyen,&nbsp;Man Po Lee,&nbsp;Do Duy Cuong,&nbsp;Yu Jiun Chan,&nbsp;Jun Yong Choi,&nbsp;Jeremy Ross,&nbsp;Matthew Law","doi":"10.3851/IMP3379","DOIUrl":"https://doi.org/10.3851/IMP3379","url":null,"abstract":"<p><strong>Background: </strong>Comprehensive treatment and clinical management are central to improving outcomes for people living with HIV (PLHIV). We explored trends in HIV clinical care, treatment outcomes, and chronic kidney disease (CKD) and diabetes monitoring.</p><p><strong>Methods: </strong>We included patients ≥18 years in care at ten clinical sites in eight Asian countries. Proportions of patients on antiretroviral therapy (ART), with annual viral load, and with viral load suppression (VLS; <1,000 copies/ml) were estimated by year for 2011-2016, stratified by country income level (lower-middle income [LMIC] and high-income countries [HIC]). Among those on ART in 2016 we evaluated factors associated with annual CKD and diabetes monitoring.</p><p><strong>Results: </strong>Among 31,346 patients (67% male), the proportions of patients on ART (median ART initiation year 2011, IQR 2007-2013), with annual viral load and VLS had substantially increased by 2016 (to 94%, 42% and 92%, respectively, in LMIC and 95%, 97% and 93%, respectively, in HIC) with the larger increases over time seen in LMIC. Among those on ART in 2016, monitoring proportions in LMIC were 53% for CKD and 26% for diabetes compared with 83% and 59%, respectively, in HIC. Overall, a decreased odds of monitoring was observed for male gender, heterosexual HIV exposure, no viral load and LMIC. Diabetes monitoring was also decreased in those with viral failure.</p><p><strong>Conclusions: </strong>Our findings highlight suboptimal monitoring of viral load, CKD and diabetes in PLHIV in Asia. There is a need for affordable and scalable monitoring options to improve the joint care for HIV and non-communicable diseases.</p>","PeriodicalId":8364,"journal":{"name":"Antiviral Therapy","volume":"25 5","pages":"275-285"},"PeriodicalIF":1.2,"publicationDate":"2020-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8272912/pdf/nihms-1721633.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38754729","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}

{"title":"The effects of nucleoside/nucleotide analogues on host immune cells: the baseline for future immune therapy for HBV?","authors":"Lauke L Boeijen,&nbsp;Michelle Spaan,&nbsp;André Boonstra","doi":"10.3851/IMP3364","DOIUrl":"https://doi.org/10.3851/IMP3364","url":null,"abstract":"<p><p>HBV is a non-cytopathic virus and the progression of liver fibrosis is attributed to the host immune response. Complete suppression of viral replication using nucleotide or nucleoside analogues (NUCs) can prevent most complications related to chronic HBV infection. Unfortunately, antiviral treatment has to be administered lifelong to the majority of patients as HBV persists in the hepatocytes. However, although NUCs are very frequently administered in clinical practice, their effects on vital parts of the host immune response to HBV are not well established. In this review we summarize the currently available data gathered from longitudinal studies that investigated treatment-associated alterations of HBV-specific CD4⁺ and CD8⁺ T-cells, regulatory T-cells and natural killer (NK) cells. These observations are important, as they can guide the design of studies that investigate the efficacy of new immune therapeutic agents. Novel experimental compounds will likely be added to ongoing NUC treatment, which leads to a functional cure in only a small minority of patients.</p>","PeriodicalId":8364,"journal":{"name":"Antiviral Therapy","volume":"25 4","pages":"181-191"},"PeriodicalIF":1.2,"publicationDate":"2020-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38093132","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":"COVID-19 and hepatitis B infection.","authors":"Saleh A Alqahtani,&nbsp;Maria Buti","doi":"10.3851/IMP3382","DOIUrl":"https://doi.org/10.3851/IMP3382","url":null,"abstract":"<p><p>The 2019 coronavirus disease (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has emerged as a major burden worldwide, resulting in serious public health challenges. HBV infection is another widely spread virus that chronically affects about 257 million people. The management of patients with HBV infection has gained attention in the context of the COVID-19 pandemic. Patients with COVID-19 have varying levels of liver involvements, resulting from direct viral effects on the liver as well as hepatotoxic drugs. This was demonstrated by elevated levels of liver enzymes, particularly evident in those patients with severe SARS-CoV-2 infection. However, scarce information is available on the management of COVID-19 patients having an underlying chronic liver disease, including HBV infection. Studies have shown reactivation of HBV infection following treatment with tocilizumab and corticosteroids, emphasizing the need for caution when using these agents to treat COVID-19 patients with HBV infection. HBV screening and prophylaxis should be considered in patients with elevated transaminase levels and also in high prevalence populations. In patients with advanced liver disease, attention must be given to minimize the risk of liver decompensation. Nevertheless, further investigation is needed to enable an evidence-based approach for the care of these patients.</p>","PeriodicalId":8364,"journal":{"name":"Antiviral Therapy","volume":"25 8","pages":"389-397"},"PeriodicalIF":1.2,"publicationDate":"2020-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"25392881","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":"Short-term neuropsychiatric tolerability of bictegravir combined with emtricitabine/tenofovir alafenamide in clinical practice.","authors":"Christian Hoffmann,&nbsp;Knud Schewe,&nbsp;Stefan Fenske,&nbsp;Thomas Buhk,&nbsp;Michael Sabranski,&nbsp;Axel Adam,&nbsp;Stefan Hansen,&nbsp;Hans-Jürgen Stellbrink","doi":"10.3851/IMP3351","DOIUrl":"https://doi.org/10.3851/IMP3351","url":null,"abstract":"<p><strong>Background: </strong>Neuropsychiatric AEs (NPAEs) leading to dolutegravir (DTG) discontinuation were seen more frequently in real-world use than in randomized clinical trials (RCTs). The recently approved fixed-dose combination bictegravir plus emtricitabine and tenofovir alafenamide (BIC/F/TAF) has shown comparable NPAE rates but some favourable patient-reported outcomes in RCTs compared with DTG. We were interested in its neuropsychiatric tolerability in clinical practice.</p><p><strong>Methods: </strong>All patients starting BIC/F/TAF from June 2018 in a single centre (two subcentres) were followed retrospectively. Discontinuation rates due to any AEs and NPAEs were compared with those of patients initiating DTG-based regimens.</p><p><strong>Results: </strong>As of May 2019, a total of 943 patients (852 males, 76 females, 15 transgender and gender diverse) initiated BIC/F/TAF outside RCTs. After a median follow-up of 6.2 months, 50 (5.3%) and 31 (3.3%) patients had discontinued BIC/F/TAF due to any AEs or to NPAEs, respectively. In multivariate analysis, a pre-existing depression and subcentre remained predictive for NPAEs, but not age, gender, ethnicity or prior DTG-related AEs. Compared with 1,043 patients treated with DTG-based regimens, the estimated NPAE-related discontinuation rate with BIC/F/TAF was comparable during the first 6 months (P=0.36). Cross-intolerance was low, and only 5/55 patients with prior DTG intolerability had to discontinue BIC/F/TAF due to NPAEs.</p><p><strong>Conclusions: </strong>Short-term tolerability of BIC/F/TAF was comparable to DTG-containing regimens. As seen with DTG, discontinuation rates were higher than in RCTs. A pre-existing depression but also physician's awareness may have an impact on tolerability and continuation of BIC/F/TAF. In contrast, prior intolerability of DTG was of limited predictive value.</p>","PeriodicalId":8364,"journal":{"name":"Antiviral Therapy","volume":"25 2","pages":"83-90"},"PeriodicalIF":1.2,"publicationDate":"2020-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"37790464","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":"Antiviral activity of PLK1-targeting siRNA delivered by lipid nanoparticles in HBV-infected hepatocytes.","authors":"Adrien Foca, Ammen Dhillon, Thomas Lahlali, Julie Lucifora, Anna Salvetti, Michel Rivoire, Amy Lee, David Durantel","doi":"10.3851/IMP3361","DOIUrl":"10.3851/IMP3361","url":null,"abstract":"<p><strong>Background: </strong>A link between HBV and PLK1 was clearly evidenced in HBV-driven carcinogenesis, and we have also recently shown that PLK1 is a proviral factor in the early phases of HBV infection. Moreover, we have shown that BI-2536, a small molecule PLK1 inhibitor, was very efficient at inhibiting HBV DNA neosynthesis, notably by affecting nucleocapsid assembly as a result of the modulation of HBc phosphorylation. Yet, as small molecule kinase inhibitors often feature poor selectivity, a more specific and safer strategy to target PLK1 would be needed for a potential development against chronic HBV infections.</p><p><strong>Methods: </strong>Here, we analysed using both freshly isolated primary human hepatocytes and differentiated HepaRG, the anti-HBV properties of an LNP-encapsulated PLK1-targeting siRNA. Standard assays were used to monitor the effect of LNP siPLK1, or controls (LNP siHBV and LNP siNon-targeting), on HBV replication and cell viability.</p><p><strong>Results: </strong>A dose as low as 100 ng/ml of LNP-siPLK1 resulted in a >75% decrease in secreted HBV DNA (viral particles), which was comparable to that obtained with LNP siHBV or 10 µM of tenofovir (TFV), without affecting cell viability. Interestingly, and in contrast to that obtained with TFV, a strong inhibition of viral RNA and HBe/HBsAg secretions was also observed under LNP siPLK1 treatment. This correlated with a significant intracellular decrease of vRNA accumulation, which was independent of any change in cccDNA levels, thus suggesting a transcriptional or post-transcriptional modulation. Such an effect was not obtained with a biochemical approach of PLK1 inhibition, suggesting an enzymatic-independent role of PLK1.</p><p><strong>Conclusions: </strong>This study emphasizes that a specific PLK1 inhibition could help in achieving an improved HBsAg loss in CHB patients, likely in combination with other HBsAg-targeting strategies.</p>","PeriodicalId":8364,"journal":{"name":"Antiviral Therapy","volume":"25 3","pages":"151-162"},"PeriodicalIF":1.2,"publicationDate":"2020-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38012141","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":"Long-term outcomes in Chinese patients with chronic hepatitis B receiving nucleoside/nucleotide analogue therapy in real-world clinical practice: 5-year results from the EVOLVE study.","authors":"Jidong Jia,&nbsp;Jia Shang,&nbsp;Hong Tang,&nbsp;Jiaji Jiang,&nbsp;Qin Ning,&nbsp;Xiaoguang Dou,&nbsp;Shuqin Zhang,&nbsp;Mingxiang Zhang,&nbsp;Tao Han,&nbsp;Deming Tan,&nbsp;Xinmin Zhou,&nbsp;Guoliang Chen,&nbsp;Jifang Sheng,&nbsp;Zhijun Su,&nbsp;Haijun Chen,&nbsp;Erhei Dai,&nbsp;Yinong Ye,&nbsp;Ying Guo,&nbsp;Yuefei Shen,&nbsp;Jing Yuan,&nbsp;Zhen Wei,&nbsp;Siyun Zhu","doi":"10.3851/IMP3372","DOIUrl":"https://doi.org/10.3851/IMP3372","url":null,"abstract":"<p><strong>Background: </strong>In China, the optimal management of individuals living with chronic HBV infection (CHB) remains an unmet need. The EVOLVE Study was a 5-year prospective, longitudinal, observational study that compared the clinical outcomes in treatment-naive CHB patients receiving entecavir (ETV) or lamivudine (LAM)-based therapies.</p><p><strong>Methods: </strong>Males or females aged ≥18 years, diagnosed with CHB regardless of cirrhosis or hepatitis B e antigen (HBeAg) status were enrolled from tier 2 city hospitals (between 2012-2014). The choice of initial therapy and subsequent treatment modifications was at the discretion of treating physicians. Key outcomes included treatment modifications, virological response (HBV DNA <300 copies/ml) and HBV disease progression.</p><p><strong>Results: </strong>Of the 3,408 patients enrolled, 1,807 and 628 received ETV and LAM-based therapy, respectively. The mean age was 39.5 years, 74% were male and 22.9% had cirrhosis. The rate of treatment modification was higher in the LAM-based versus ETV group (25.9% versus 13.7%); viral breakthrough was the most common reason in the LAM-based group versus financial reasons in the ETV group. At week 240, the virological response rate was 73% in both treatment groups. Compared with LAM-based therapy, ETV was associated with a significantly lower incidence of viral breakthrough (12.6% versus 2.1%) and genotypic resistance (10.1% versus 1.2%; P<0.0001 for both); significantly lower risk of HBV disease progression (14.0% versus 10.7%; P=0.0113); and lower rates of progression to decompensated cirrhosis (9.6% versus 6.4%) and hepatocellular carcinoma (1.9% versus 0.8%).</p><p><strong>Conclusions: </strong>This real-world, longitudinal study demonstrated a significantly lower risk of HBV-related disease progression, viral breakthrough and resistance with ETV versus LAM-based therapy. ClinicalTrials.gov NCT01726439.</p>","PeriodicalId":8364,"journal":{"name":"Antiviral Therapy","volume":"25 6","pages":"293-304"},"PeriodicalIF":1.2,"publicationDate":"2020-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38518751","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}