Antiviral Therapy最新文献

{"title":"Pharmacokinetics, safety and tolerability of single- and multiple-ascending doses of JNJ-64530440, a novel hepatitis B virus capsid assembly modulator, in healthy volunteers","authors":"T. Kakuda, J. Yogaratnam, C. Westland, E. Gane, C. Schwabe, Jennifer Vuong, Megha Patel, J. Snoeys, W. Talloen, O. Lenz, J. Fry, S. Chanda, P. van Remoortere","doi":"10.1177/13596535211044331","DOIUrl":"https://doi.org/10.1177/13596535211044331","url":null,"abstract":"Background Pharmacokinetics and safety of JNJ-64530440, a hepatitis B virus capsid assembly modulator producing normal empty capsids (CAM-N), in healthy volunteers were evaluated. Methods This Phase I study (NCT03439488) was a double-blind, randomised, placebo-controlled study. Adults (n = 10/cohort, five Asian/five non-Asian), randomised 4:1, received single-ascending doses of oral JNJ-64530440 (first- and second-generation formulations) or placebo under fasted (50, 150, 300 and 900 mg) or fed (300, 750, 1,000, 2000 and 4000 mg) conditions. Multiple-ascending doses of 750 or 2000 mg once daily and 750 mg twice daily JNJ-64530440 (second-generation formulation) for 7 days were evaluated. Pharmacokinetic parameters were estimated from plasma concentrations. Safety was assessed throughout. Results Less than dose-proportional increases in maximum plasma concentrations (Cmax) and area under the plasma concentration–time curves (AUCs) were observed across the doses. Mean plasma half-lives ranged from 9.3 to 14.5 h. Cmax and AUC were ∼two fold higher under fed versus fasting conditions and slightly higher in Asians versus Caucasians. JNJ-64530440 doses ≥750 mg achieved plasma levels higher than protein-binding adjusted concentrations demonstrating in vitro antiviral activity. No serious adverse events (AEs), treatment discontinuations or dose-limiting toxicities were seen. AE frequency/severity did not increase with dose. Conclusions Single (up to 4000 mg) and multiple doses (up to 2000 mg for 7 days) of JNJ-64530440 were well tolerated in healthy volunteers. Multiple doses ≥750 mg/day achieved plasma concentrations expected to have antiviral activity that may lower hepatitis B surface antigen. No clinically relevant differences in tolerability or pharmacokinetic parameters were seen between Asians versus Caucasians.","PeriodicalId":8364,"journal":{"name":"Antiviral Therapy","volume":"26 1","pages":"13 - 24"},"PeriodicalIF":1.2,"publicationDate":"2021-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"45694862","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":"Comparative outcomes of lopinavir/ritonavir and hydroxychloroquine for the treatment of COVID-19 with mild-to-moderate severity: A retrospective observational study","authors":"Jeong Eun Lee, S. Lee, J. Heo, D. Kim, M. Park, Hyunjin Son, Dongkeun Kim, K. Kim, Shinwon Lee, S. H. Lee","doi":"10.1177/13596535211039394","DOIUrl":"https://doi.org/10.1177/13596535211039394","url":null,"abstract":"Background Lopinavir/ritonavir (LPV/r) and hydroxychloroquine (HCQ) are both being used to treat coronavirus disease 2019 (COVID-19), but their relative effectiveness is unknown. The purpose of this study was to compare the clinical outcomes of patients treated for COVID-19 with LPV/r or HCQ. Methods A retrospective observational study was conducted at 2 hospitals in Busan, South Korea, where approximately 90% of COVID-19 patients were hospitalised during February/March 2020. All patients aged ≥15 years that were hospitalised with mild or moderately severe COVID-19 received LPV/r or HCQ as their initial treatment and were included in the analysis. Results Among the 72 patients with mild-to-moderate disease severity on admission, 45 received LPV/r and 27 received HCQ as their initial therapy. A higher proportion of the LPV/r group had pneumonia on admission (LPV/r, 49% vs HCQ, 15%), but there were no other significant differences in the demographic or clinical characteristics between groups. Switching therapy due to clinical failure was significantly more common in the HCQ group than in the LPV/r group (41% [11/27] and 2% [1/45], respectively, P = .001). Disease progression was also significantly more common in the HCQ group than in the LPV/r group (44% [12/27] and 18% [8/45], respectively, P = .030). Conclusion Based on our study results, HCQ shows no apparent advantage compared to LPV/r for preventing progression to severe disease in patients with COVID-19.","PeriodicalId":8364,"journal":{"name":"Antiviral Therapy","volume":"26 1","pages":"34 - 42"},"PeriodicalIF":1.2,"publicationDate":"2021-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"44320602","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 effect of Artemisia aucheri aqueous extract on UL46 and US6 genes of HSV-1","authors":"M. Zamanian, Z. Sharifi, Z. Noormohammadi, T. Akbarzadeh, F. Bineshian","doi":"10.1177/13596535211039907","DOIUrl":"https://doi.org/10.1177/13596535211039907","url":null,"abstract":"HSV-1 is associated with oral lesions. Recently, anti-herpetic activity of different plant species has been investigated. In this study, the effects of Artemisia aucheri aqueous extract on the HSV-1 virus-infected Vero cells were assessed. The highest cell viability occurred in plant aqueous extracts was with a concentration of 75 μg/mL, 1–2 h before viral infection. The IC50 of the aqueous extract of 24.7 μg/ml was calculated. Most percentage of infected cell inhibition (89.6%) was with the chloroform fraction in concentration of 75 μg/ml, and the least percentage of infected cell inhibition (21.7%) was in concentration of 12.5 μg/ml with the ethyl acetate fraction in comparison with untreated control. Moreover, Q-PCR results revealed that the expression of genes UL46 and US6 were significantly reduced in the presence of different treatments utilized in the experiment. In conclusion, the present study proposes that aqueous extracts of medicinal plant Artemisia aucheri have anti-viral property and may be considered as a remedy for HSV-1 treatment.","PeriodicalId":8364,"journal":{"name":"Antiviral Therapy","volume":"26 1","pages":"43 - 48"},"PeriodicalIF":1.2,"publicationDate":"2021-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"48671184","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":"Higher risk of mortality in HIV-HBV co-infected patients from sub-Saharan Africa is observed at lower CD4+ cell counts","authors":"G. Kouamé, D. Gabillard, R. Moh, A. Badje, J. Ntakpé, A. Emième, S. Maylin, T. Toni, H. Menan, F. Zoulim, C. Danel, X. Anglaret, S. Eholie, K. Lacombe, A. Boyd","doi":"10.1177/13596535211039589","DOIUrl":"https://doi.org/10.1177/13596535211039589","url":null,"abstract":"Background Hepatitis B virus (HBV) co-infection in human immunodeficiency virus (HIV)-positive individuals increases the risk of overall mortality, especially when HBV DNA levels are high. The role of CD4+ cell counts in this association is poorly defined. We aimed to determine whether HIV–HBV co-infection influences changes in CD4+ cell count before and during antiretroviral therapy and whether it affects mortality risk at levels of CD4+. Methods 2052 HIV-positive participants from Côte d’Ivoire in a randomized-control trial assessing early or deferred ART were included. HBV-status was determined by hepatitis B surface antigen (HBsAg). Changes in CD4+ cell levels were estimated using a mixed-effect linear model. The incidence rates of all-cause mortality were estimated at CD4+ counts ≤350, 351–500, >500/mm3 and were compared between HBV-status groups as incidence rate ratios (IRR). Results At baseline, 190 (9%) were HBsAg-positive [135 (71%) with HBV DNA <2000 IU/mL, 55 (29%) ≥2000 IU/mL]. Follow-up was a median 58 months (IQR = 40–69). Between co-infection groups, there were no differences in CD4+ decline before ART initiation and no differences in CD4+ increase after ART initiation. After adjusting for sex, age, baseline HIV RNA level, and early/deferred ART arm, mortality rates were not significantly different between HBsAg-positive versus HBsAg-negative participants across strata of CD4+ levels. However, HBsAg-positive individuals with HBV-DNA ≥2000 IU/mL versus HBsAg-negative individuals had increased mortality rates at ≤350/mm3 (adjusted-IRR = 3.82, 95% CI = 1.11–9.70) and 351–500/mm3 (adjusted-IRR = 4.37, 95% CI = 0.98–13.02), but not >500/mm3 (adjusted-IRR = 1.07, 95% CI = 0.01–4.91). Conclusion Despite no effect of HBV-infection on CD4+ levels, HIV-HBV co-infected individuals with high HBV replication are at higher risk of mortality when CD4+ is <500/mm3.","PeriodicalId":8364,"journal":{"name":"Antiviral Therapy","volume":"26 1","pages":"25 - 33"},"PeriodicalIF":1.2,"publicationDate":"2021-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"43499172","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":"Virus reactivation in a non-cirrhotic HBV patient requiring liver transplantation after cessation of nucleoside analogue therapy","authors":"Han Zhang, Fang Chen, E. Giang, Fei Bao, G. Lauer, C. Marsh, M. Law, P. Pockros","doi":"10.1177/13596535211042205","DOIUrl":"https://doi.org/10.1177/13596535211042205","url":null,"abstract":"Nucleos(t)ide analogues (NAs) are a mainstay of therapy for chronic hepatitis B (CHB) infections and have a profound effect on hepatitis B virus (HBV) suppression. We report a rare case of HBV reactivation in a CHB patient without cirrhosis following cessation of NA therapy that resulted in acute liver failure requiring liver transplantation. Investigation of the viral genetics and host immune responses suggest that viral mutations known to promote virus replication are associated with reactivation, whereas adaptive immunity to HBV remained defective in this patient. Viral sequencing may be useful for identifying mutations that are unfavorable for therapy withdrawal.","PeriodicalId":8364,"journal":{"name":"Antiviral Therapy","volume":"26 1","pages":"3 - 8"},"PeriodicalIF":1.2,"publicationDate":"2021-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"46315134","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 1,4-disubstituted-1,2,3-triazoles against HSV-1 in vitro.","authors":"Daiane J Viegas,&nbsp;Verônica D da Silva,&nbsp;Camilla D Buarque,&nbsp;David C Bloom,&nbsp;Paula A Abreu","doi":"10.3851/IMP3387","DOIUrl":"https://doi.org/10.3851/IMP3387","url":null,"abstract":"<p><strong>Background: </strong>Herpes simplex virus 1 (HSV-1) affects a large part of the adult population. Anti-HSV-1 drugs, such as acyclovir, target thymidine kinase and viral DNA polymerase. However, the emerging of resistance of HSV-1 alerts for the urgency in developing new antivirals with other therapeutic targets. Thus, this study evaluated a series of 1,4-disubstituted-1,2,3-triazole derivatives against HSV-1 acute infection and provided deeper insights into the possible mechanisms of action.</p><p><strong>Methods: </strong>Human fibroblast cells (HFL-1) were infected with HSV-1 17syn+ and treated with the triazole compounds at 50 μM for 24 h. The 50% effective drug concentration (EC₅₀) was determined for the active compounds. Their cytotoxicity was also evaluated in HFL-1 with the 50% cytotoxic concentration (CC₅₀) determined using CellTiter-Glo^® solution. The most promising compounds were evaluated by virucidal activity and influence on virus egress, DNA replication and transcription, and effect on an acyclovir-resistant HSV-1 strain.</p><p><strong>Results: </strong>Compounds 3 ((E)-4-methyl-N'-(2-(4-(phenoxymethyl)-1H-1,2,3-triazol1yl)benzylidene)benzenesulfonohydrazide) and 4 (2,2'-(4,4'-((1,3-phenylenebis(oxy))bis(methylene))bis(1H-1,2,3-triazole-4,1 diyl)) dibenzaldehyde) were the most promising, with an EC₅₀ of 16 and 21 μM and CC₅₀ of 285 and 2,593 μM, respectively. Compound 3 was able to inhibit acyclovir-resistant strain replication and to interfere with virus egress. Both compounds did not affect viral DNA replication, but inhibited significantly the expression of ICP0, ICP4 and gC. Compound 4 also affected the transcription of UL30 and ICP34.5.</p><p><strong>Conclusions: </strong>Our findings demonstrated that these compounds are promising antiviral candidates with different mechanisms of action from acyclovir and further studies are merited.</p>","PeriodicalId":8364,"journal":{"name":"Antiviral Therapy","volume":"25 8","pages":"399-410"},"PeriodicalIF":1.2,"publicationDate":"2020-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"25464094","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":"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}