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Background: The recommended treatment for patients infected with hepatitis C virus genotype 2 (HCV2) is pegylated interferon (peginterferon) and ribavirin for 24 weeks. Aim: To assess whether a shorter 16-week treatment is as effective as a standard 24-week treatment. Methods: Patients with HCV2 infection were randomised in a 1:2 ratio to either 16 weeks (n = 50) or 24 weeks (n = 100) of treatment with peginterferon α-2a (180 μg/week) and weight-based ribavirin 1000–1200 mg/day, with a 24-week follow-up period. A rapid virological response (RVR) was defined as seronegative for HCV RNA at 4 weeks of treatment, and the primary end point, sustained virological response (SVR), as seronegative for HCV RNA at the 24-week follow-up. Results: The rate of RVR and SVR was 86% (43/50, 95% confidence interval (CI) 76% to 96%) and 94% (47/50, CI 87% to 100%), respectively, in the 16-week group, which was comparable to 87% (87/100, CI 80% to 94%) and 95% (95/100, CI 91% to 99%) in the 24-week group. Patients with RVR had a significantly higher SVR rate than patients without RVR in both 16-week (100% vs 57%, p = 0.015) and 24-week groups (98% vs 77%, p = 0.002). Multivariate analysis showed that RVR and age were independent factors associated with SVR. Both treatment arms were equally well tolerated. The incidence of alopecia was significantly higher in the 24-week group (49%) than in the 16-week group (20%, p = 0.001). Conclusion: 16 weeks and 24 weeks of peginterferon treatment with weight-based ribavirin at a dose of 1000–1200 mg/day provided equal efficacy in patients with HCV2 who achieved RVR at 4 weeks.

Objective: To determine the frequency of sustained virological response (SVR) after treatment with Sofosbuvir and daclatasvir among hepatitis C positive hemodialysis patients presenting to a tertiary care hospital. Study Design: Descriptive case series. Place and Duration of Study: Department of Nephrology, Sharif Medical City, Lahore Pakistan, from Mar to Dec 2019. Methodology: Total 62 hepatitis C positive hemodialysis patients undergoing regular hemodialysis in the Heamodialysis unit of Sharif Medical City, Lahore and fulfilling the selection criteria were enrolled in the study after an informed consent. Information regarding their demographic data was noted in the proforma. All the patients were advised 400 mg of sofosbuvir on alternate day along with 60mg daclatasvir once daily for 12 weeks. At the end of 12 weeks of therapy, all patients were undergone qualitative PCR and effectiveness of the treatment was noted on the basis of qualitative PCR. In order to see SVR 12 PCR was repeated after 12 weeks and SVR labeled as operational definition. Results: Total 62 patients were enrolled in the study. Their mean age was 36.52±14.03 years with range from 15-60 years. The minimum duration of dialysis was 3 months and maximum was 10 months. Body mass index ranged from 25-32 kg/m2with mean 28.37±2.29 kg/m2. There were 53.2% male patients and 46.8% were female patients. SVR-12 was achieved in 82.3% patients while 17.7% patients failed to respond No association was found between SVR-12 and age, sex, BMI or duration...Conclusion: Treatment with Sofosbuvir and daclatasvir among hepatitis C positive ...

Direct-acting antivirals (DAAs) induce a rapid virologic response (SVR) in up to 99% of chronic hepatitis C patients. The role of SVR by DAAs on the incidence or recurrence of hepatocellular carcinoma (HCC) is still a matter of debate, although it is known that SVR does not eliminate the risk of HCC. In this review, we made an updated analysis of the literature data on the impact of SVR by DAAs on the risk of HCC as well as an assessment of risk factors and the role of epigenetics. Data showed that SVR has no impact on the occurrence of HCC in the short–medium term but reduces the risk of HCC in the medium–long term. A direct role of DAAs in the development of HCC has not been demonstrated, while the hypothesis of a reduction in immune surveillance in response to the rapid clearance of HCV and changes in the cytokine pattern influencing early carcinogenesis remains to be further elucidated. HCV induces epigenetic alterations such as modifications of the histone tail and DNA methylation, which are risk factors for HCC, and such changes are maintained after HCV clearance. Future epigenetic studies could lead to identify useful biomarkers and therapeutic targets. Cirrhosis has been identified as a risk factor for HCC, particularly if associated with high liver stiffness and α-fetoprotein values, diabetes and the male sex. Currently, considering the high number and health cost to follow subjects’ post-HCV clearance by DAAs, it is mandatory to identify those at high risk of HCC to optimize management.

Jinchuan Shi,1 Wenhui Zhang,1,2 Jie Han,1,2 Zhongdong Zhang,1 Dingyan Yan,1,2 Rongrong Zheng,1 Feng Li,1 Yi Wang1,3 1Department of Infection, Affiliated Hangzhou Xixi Hospital, Zhejiang Chinese Medical University, Hangzhou, 310023, People’s Republic of China; 2Department of Nursing, Affiliated Hangzhou Xixi Hospital, Zhejiang Chinese Medical University, Hangzhou, 310023, People’s Republic of China; 3Clinical Research Laboratory, Affiliated Hangzhou Xixi Hospital, Zhejiang Chinese Medical University, Hangzhou, 310023, People’s Republic of ChinaCorrespondence: Yi Wang, Clinical Research Laboratory, Affiliated Hangzhou Xixi Hospital, Zhejiang Chinese Medical University, Hangzhou, People’s Republic of China, Email wangyi_xixi@126.comObjective: Both B/F/TAF and DTG/3TC are recommended in treatment guidelines for switch therapy in PLWH. This study aimed to evaluate the safety and metabolic health consequences of two switched regimens in a real-world setting among virologically suppressed PLWH previously treated with EFV/TDF/3TC.Methods: This retrospective real-world study in Hangzhou included 220 virologically suppressed PLWH who switched from EFV/TDF/3TC to DTG/3TC or B/F/TAF between January 1, 2020 and October 30, 2023. All participants were examined the changes in weight, BMI, GLU levels, lipid parameters (TC, LDL-C, HDL-C, and TG), and eGFR at post-12-month.Results: The mean age of included participants was 50.8 years (SD: 11.3). After 12 months of switching, the HIV RNA level was below the limit of detection (< 20 copies/mL) among all participants. The switch to DTG/3TC or B/F/TAF therapy was associated with significant improvement in LDL-C, GLU levels, and eGFR values (all P < 0.05), while other metabolic indexes did not change significantly. Furthermore, there was a significant difference in the incidence of hyperglycemia (5.7% vs 19.35%; P = 0.004) between the B/F/TAF and DTG/3TC groups, but not included the mean changes of weight, BMI, lipid profiles, GLU levels, and eGFR and incidence of high TC and high TG. For the aged 40– 59 years and aged ≥ 60 years PLWH, the differences in metabolic indicators were minimal between DTG/3TC and B/F/TAF groups post-12-month, with no significant differences between the arms in mean change from baseline in TC, TG, HDL-C, LDL-C, GLU, BMI, weight, and eGFR.Conclusion: In this study, the B/F/TAF or DTG/3TC regimens are safe for virologically suppressed PLWH aged > 40 years. The transition to B/F/TAF demonstrated dual clinical benefits, significantly reducing hyperglycemia incidence while preserving renal function.Keywords: people living with HIV, virological suppression, antiretroviral therapy, metabolic indices

Despite immense progress in antiretroviral therapy (ART) scale-up, many people still lack access to basic standards of care, with our ability to meet the Joint United Nations Programme on HIV/AIDS 90-90-90 treatment targets for HIV/AIDS dependent on dramatic improvements in diagnostics. The World Health Organization recommends routine monitoring of ART effectiveness using viral load (VL) testing at 6 months and every 12 months, to monitor treatment adherence and minimize failure, and will publish its VL toolkit later this year. However, the cost and complexity of VL is preventing scale-up beyond developed contries and there is a lack of awareness among clinicians as to the long-term patient benefits and its role in prolonging the longevity of treatment programs. With developments in this diagnostic field rapidly evolving—including the recent improvements for accurately using dried blood spots and the imminent appearance to the market of point-of-care technologies offering decentralized diagnosis—we describe current barriers to VL testing in resource-limited settings. Effective scale-up can be achieved through health system and laboratory system strengthening and test price reductions, as well as tackling multiple programmatic and funding challenges.

Background：Entecavir （ETV） has been shown to be effective in randomized controlled trials in highly selected patients with hepatitis B virus （HBV） infection.This study aimed to evaluate the efficacy of ETV in chronic hepatitis B （CHB） patients in the real-world setting.Methods：A total of 233 treatment-na（i）ve,CHB patients who received at least 12 months of ETV treatment were included in this retrospective study.Rates of virological response （VR）,hepatitis B s antigen （HBsAg） loss,hepatitis B e antigen （HBeAg） clearance/seroconversion,virological breakthrough,cirrhosis,and hepatocellular carcinoma were evaluated.Results：Of 233 patients,175 patients were male,with mean age of 43 years old,and 135 patients were HBeAg positive.The mean baseline levels of serum alanine aminotransferase and HBV DNA in all patients were 230 U/L and 6.6 log 10 IU/ml,respectively.The mean follow-up period was 28 months.The cumulative rates of achieving VR increased from 3.4% at 3 months to 94.4% at 60 months.Primary nonresponse occurred in 3 （1.3%） patients.Partial VR （PVR） occurred in 61 （26.2%） patients at 12 months.The baseline serum HBV DNA level （hazard ratio [HR],2.054;P 〈 0.001） was an independent risk factor for PVR.HBsAg loss did not occur.The cumulative rates of HBeAg clearance increased from 2.2% at 3 months to 28.2% at 60 months.PVR was the significant determinant of HBeAg clearance （HR,0.341;P =0.026）.Age （HR,1.072;P =0.013） and PVR （HR,5.131;P =0.017） were the significant determinants of cirrhosis.Conclusions：ETV treatment was effective for HBV DNA suppression in this study,but HBsAg loss and HBeAg clearance/seroconversion rates were lower compared with previous clinical trials.PVR was associated with HBeAg clearance and cirrhosis.

Background Despite the growing number of people on antiretroviral therapy (ART), there is limited information about virological non-suppression and its determinants among HIV-positive (HIV+) individuals enrolled in HIV care in many resource-limited settings. We estimated the proportion of virologically non-suppressed patients, and identified the factors associated with virological non-suppression. Methods We conducted a descriptive cross-sectional study using routinely collected program data from viral load (VL) samples collected across the country for testing at the Central Public Health Laboratories (CPHL) in Uganda. Data were generated between August 2014 and July 2015. We extracted data on socio-demographic, clinical and VL testing results. We defined virological non-suppression as having ≥1000 copies of viral RNA/ml of blood for plasma or ≥5000 copies of viral RNA/ml of blood for dry blood spots. We used logistic regression to identify factors associated with virological non-suppression. Results The study was composed of 100,678 patients; of these, 94,766(94%) were for routine monitoring, 3492(4%) were suspected treatment failures while 1436(1%) were repeat testers after suspected failure. The overall proportion of non-suppression was 11%. Patients on routine monitoring registered the lowest (10%) proportion of non-suppressed patients. Virological non-suppression was higher among suspected treatment failures (29%) and repeat testers after suspected failure (50%). Repeat testers after suspected failure were six times more likely to have virological non-suppression (OR adj  = 6.3, 95%CI = 5.5–7.2) when compared with suspected treatment failures (OR adj  = 3.3, 95%CI = 3.0–3.6). The odds of virological non-suppression decreased with increasing age, with children aged 0–4 years (OR adj  = 5.3, 95%CI = 4.6–6.1) and young adolescents (OR adj  = 4.1, 95%CI = 3.7–4.6) registering the highest odds. Poor adherence (OR adj  = 3.4, 95%CI = 2.9–3.9) and having active TB (OR adj  = 1.9, 95%CI = 1.6–2.4) increased the odds of virological non-suppression. However, being on second/third line regimens (OR adj  = 0.86, 95%CI = 0.78–0.95) protected patients against virological non-suppression. Conclusion Young age, poor adherence and having active TB increased the odds of virological non-suppression while second/third line ART regimens were protective against non-suppression. We recommend close follow up and intensified targeted adherence support for repeat testers after suspected failure, children and adolescents.

There is a high medical need for an interferon-free, all-oral, short-duration therapy for hepatitis C virus (HCV) that is highly effective across diverse patient populations, including patients with cirrhosis or previous null response to pegylated interferon (peginterferon) plus ribavirin (PR-null responders). We aimed to assess the efficacy, safety, and effective treatment duration of grazoprevir (an HCV NS3/4A protease inhibitor) combined with elbasvir (an HCV NS5A inhibitor) with or without ribavirin in patients with HCV genotype 1 infection with baseline characteristics of poor response. The C-WORTHY trial is a randomised, open-label phase 2 trial of grazoprevir plus elbasvir with or without ribavirin; here we report findings for two cohorts of previously untreated patients with cirrhosis (cohort 1) and those with previous PR-null response with or without cirrhosis (cohort 2) enrolled in part B of the study. Eligible patients were adults aged 18 years or older with chronic HCV genotype 1 infection and HCV RNA concentrations of 10 000 IU/mL or higher in peripheral blood. We randomly assigned patients to receive grazoprevir (100 mg daily) and elbasvir (50 mg daily) with or without ribavirin for 12 or 18 weeks. Randomisation was done centrally with an interactive voice response system; patients and study investigators were masked to treatment duration up to week 12 but not to treatment allocation. The primary endpoint was the proportion of patients achieving HCV RNA less than 25 IU/mL at 12 weeks after end of treatment (SVR12), assessed by COBAS TaqMan version 2.0. This study is registered with ClinicalTrials.gov, number NCT01717326. We describe findings for 253 patients enrolled in cohort 1 (n=123) or cohort 2 (n=130). In cohort 1, we randomly assigned 60 patients to the 12-week regimen (31 with ribavirin and 29 with no ribavirin) and 63 to the 18-week regimen (32 with ribavirin and 31 with no ribavirin); in cohort 2, we randomly assigned 65 patients to the 12-week regimen (32 with ribavirin and 33 with no ribavirin) and 65 to the 18-week regimen (33 with ribavirin and 32 with no ribavirin. High SVR12 rates were achieved irrespective of the use of ribavirin or extension of the treatment duration from 12 to 18 weeks; SVR12 rates ranged from 90% (95% CI 74–98; 28/31; cohort 1, 12 weeks, ribavirin-containing) to 100% (95% CI 89–100; 33/33; cohort 2, 18 weeks, ribavirin-containing). Among patients treated for 12 weeks with grazoprevir plus elbasvir without ribavirin, 97% (95% CI 82–100, 28/29) of patients in cohort 1 and 91% (76–98, 30/33) of patients in cohort 2 achieved SVR12. Adverse events reported in more than 10% of patients were fatigue (66 patients, 26% [95% CI 21–32]), headache (58 patients, 23% [95% CI 18–29]), and asthenia (35 patients, 14% [95% CI 10–19]). Treatment with grazoprevir plus elbasvir, both with and without ribavirin and for both 12 and 18 weeks' treatment duration, showed high rates of efficacy in previously untreated patients with cirrhosis and previous PR-null responders with and without cirrhosis. These results support the phase 3 development of grazoprevir plus elbasvir. Merck & Co, Inc.

Background. More than 11.7 million people are currently receiving antiretroviral therapy (ART) in low- and middle-income countries (LMICs), and focused efforts are needed to ensure high levels of adherence and to minimize treatment failure. Recently, international targets have emphasized the importance of long-term virological suppression as a key measure of program performance. Methods. We systematically reviewed publications and conference abstracts published between January 2006 and May 2013 that reported virological outcomes among human immunodeficiency virus type 1 (HIV-1)–infected adults receiving first-line ART for up to 5 years in LMICs. Summary estimates of virological suppression after 6, 12, 24, 36, 48, and 60 months of ART were analyzed using random-effects meta-analysis. Intention-to-treat (ITT) analysis assumed all participants who were lost to follow-up, died, or stopped ART as having virological failure. Results. Summary estimates of virological suppression remained >80% for up to 60 months of ART for all 184 included cohorts. ITT analysis yielded 74.7% (95% confidence interval [CI], 72.2–77.2) suppression after 6 months and 61.8% (95% CI, 44.0–79.7) suppression after 48 months on ART. Switches to second-line ART were reported scarcely. Conclusions. Among individuals retained on ART, virological suppression rates during the first 5 years of ART were high (>80%) and stable. Suppression rates in ITT analysis declined during 4 years.

Background and aimChronic HCV infection is associated with several extrahepatic manifestations (EHMs). Data on the effect of sustained virological response (SVR) on the risk of EHMs are limited.MethodsWe conducted a retrospective cohort study using data of patients from the US Veterans Affairs HCV Clinical Case Registry who had a positive HCV RNA test (10/1999-08/2009). Patients receiving interferon-based antiviral therapy (AVT) were identified. SVR was defined as negative HCV RNA at least 12 weeks after end of AVT. Risks of eight incident EHMs were evaluated in Cox regression models.ResultsOf the 160 875 HCV-infected veterans, 31 143 (19.4%) received AVT, of whom 10 575 (33.9%) experienced SVR. EHM risk was reduced in the SVR group compared with untreated patients for mixed cryoglobulinaemia (adjusted HR (aHR)=0.61; 95% CI 0.39 to 0.94), glomerulonephritis (aHR=0.62; 95% CI 0.48 to 0.79), porphyria cutanea tarda (PCT) (aHR=0.41; 95% CI 0.20 to 0.83), non-Hodgkin’s lymphoma (NHL) (aHR=0.64; 95% CI 0.43 to 0.95), diabetes (aHR=0.82; 95% CI 0.76 to 0.88) and stroke (aHR=0.84; 95% CI 0.74 to 0.94), but not for lichen planus (aHR=1.11; 95% CI 0.78 to 1.56) or coronary heart disease (aHR=1.12; 95% CI 0.81 to 1.56). Risk reductions were also observed when patients with SVR were compared with treated patients without SVR for mixed cryoglobulinaemia, glomerulonephritis, PCT and diabetes. Significant reductions in the magnitude of aHRs towards the null with increasing time to initiation of AVT after HCV diagnosis were observed for glomerulonephritis, NHL and stroke.ConclusionsRisks of several EHMs of HCV infection are reduced after AVT with SVR. However, early initiation of AVT may be required to reduce the risk of glomerulonephritis, NHL and stroke.