High Pretreatment Viral Load Research Articles

Effectiveness of Ledipasvir-Sofosbuvir 12 Weeks After Hepatitis C Virus Genotype 1 Infection and the Factors Associated With Sustained Virologic Response: A Retrospective Study.

The combination of ledipasvir and sofosbuvir (LDV/SOF) has been licensed to treat genotype 1 hepatitis C virus infection (HCV) with a 12-week regimen. However, there is scant data from Yemenregarding this combination regimen. Here, we investigate sustained virologic responses (SVR) 12 weeks after HCV treatment with LDV/SOF regimens and the factors that contribute to SVR failure. A retrospective cross-sectional study was conducted at Althora General Hospital in Ibb, Yemen, from June 1, 2019, to October 31, 2022, on 53 cases with HCV genotype 1 infection who received combined therapy of LDV/SOF and completed treatment for 12 weeks. The clinical characteristics and treatment follow-up were obtained from patient medical records. Factors associated with SVR failure were investigated in univariate analysis with odds ratio (OR) and 95% confidence interval (CI). The mean age was 50 ± 15.3 years, and most cases were female (n=36, 67.9%). Comorbidities were diabetes, hypertension, and fatty liver, which were represented in 12 (22.6%), nine (17.0%), and eight (15.1%) cases, respectively. A total of 13 (24.5%) patients had compensated liver cirrhosis, while the remaining 40 patients (75.5%) were non-cirrhotic healthy individuals. The baseline viral load (HCV RNA) was more than 800000 IU/mL in 21 patients (39.6%). Early virological response (ERV) was achieved in 51 patients (96.2%). After treatment, 46 of the patients (86.8%) achieved SVR at Week 12, while failure occurred in two patients (3.8%) and relapse occurred in five patients (9.4%). Blood liver enzymes, including alanine aminotransferase, aspartate aminotransferase, and alkaline phosphatase, returned to normal, with statistically significant improvements in non-cirrhotic healthy persons than compensated liver cirrhosis individuals (p= 0.006, 0.006, and 0.010; respectively). Factors associated with SVR failure were older age (OR:1.13; 95% CI: 1.03-1.30, p=0.009), presence of liver cirrhosis (OR: 5.48; 95% CI: 1.04-28.98, p=0.031), having diabetes (OR: 6.33; 95% CI: 1.19-37.93, p= 0.019), baseline higher viral load (OR: 2.27; 95% CI: 0.45-12.73, p<0.001), and not achieving EVR (OR:7.63; 95% CI: 3.77- 17.78, p= 0.009). In this study, we found that LDV/SOF regimens are effective against HCV genotype one infection, allowing for the expansion of 12-week treatment for suitable patients in clinical settings. Additionally, older age, liver cirrhosis, diabetes, higher pretreatment viral load, and non-completion of EVR were associated with SVR failure. However, due to the small number of HCV genotype 1 infected individuals in this study, more corporate data is required to get a clear conclusion.

Occult hepatitis C virus infection in hemodialysis patients who achieved a sustained virological response to directly acting antiviral drugs: is it a concern?

PurposeHepatitis C virus infection is a major health problem in hemodialysis patients. Occult HCV infection is defined as the presence of HCV-RNA in hepatocytes or peripheral blood mononuclear cells without the detection of HCV-RNA in the serum. We aimed to evaluate the prevalence and predictors of occult HCV infection among hemodialysis patients after treatment with direct-acting antiviral agents.MethodsThis research is a cross-sectional study that included 60 HCV patients maintained on regular HD patients who achieved 24 weeks of sustained virological response after treatment with direct-acting antiviral agents. Real-time PCR was performed to detect HCV-RNA in peripheral blood mononuclear cells.ResultsHCV-RNA was detected in peripheral blood mononuclear cells of three patients (5%). Occult HCV infection cases were treated by Interferon/ribavirin before direct-acting antiviral agents and two of them had raised pre-treatment alanine aminotransferase levels. Logistic regression analyses revealed that high pre-treatment viral load and raised pre-treatment alanine aminotransferase were associated with an increased risk of occult HCV infection with p value of 0.041 and 0.029, respectively.ConclusionsOccult HCV infection in hemodialysis patients who achieved sustained virological response after treatment with direct-acting antiviral agents may occur, and this may necessitate dual testing for HCV in both serum and peripheral blood mononuclear cells to ensure viral clearance.Clinical trials registrationClinicalTrials.gov NCT04719338.

Pretreatment HIV drug resistance predicts accumulation of new mutations in ART-naïve Ugandan children.

To assess the prevalence of pretreatment drug resistance (PDR) and its association with virologic outcomes after 24weeks of antiretroviral therapy (ART), within an urban cohort of Ugandan children. Prospective observational study. Baseline and 24-week assessments of viral load (VL) and genotypic drug resistance to nucleoside reverse transcriptase inhibitors (NRTI) and non-nucleoside reverse transcriptase inhibitors (NNRTI) were performed. Ninety-nine ART-naïve children (3-12years) initiated efavirenz-based ART 2015-2016 and 18/90 (20%) had baseline NRTI/NNRTI associated drug resistance mutations (DRMs). By 24weeks, 72/93 (77%) children had VL<40copies/mL and a total of 23 children had DRMs. Children with PDR accumulated new DRMs with a mean number (SD) of 1.4 (2.35) new mutations compared to 0.26 (0.98) in 67 children with wild-type virus (P=.003). High pretreatment VL and PDR (number of baseline DRMs) predicted viremia (P=.003; P=.023) as well as acquired drug resistance (P=.02; P=.04). Pretreatment drug resistance to NNRTI/NRTI was common among ART-naïve Ugandan children and predicted viremia and new resistance mutations after only 24weeks of efavirenz-based therapy. PDR may compromise long-term ART outcomes-especially when access to resistance testing and VL monitoring is poor. The long-term importance of PDR for non-NNRTI-based regimens needs further evaluation.

High Risk of Clinical Relapse in Patients With Chronic Hepatitis B Virus Infection After Cessation of Prophylactic Antiviral Therapy for Rituximab-Containing Chemotherapy.

Prophylaxis with nucleos(t)ide analogue (NA) is recommended to prevent hepatitis B virus (HBV) reactivation in hepatitis B surface antigen (HBsAg)-positive patients receiving rituximab-based B-cell depletion therapy. However, little is known about the risk of clinical relapse after withdrawal of NA. We retrospectively analyzed 77 noncirrhotic HBsAg carriers with hematological cancer who received rituximab-containing chemotherapy. All of them received either prophylactic entecavir or tenofovir therapy. The risk of clinical relapse and hepatic decompensation after cessation of NA was explored. Clinical relapse and hepatic decompensation developed in 25 (32.5 %) and 11 (14.3 %) of the patients, respectively, and 2 patients died of hepatic decompensation. Most of the hepatic events occurred within 1 year (20 of 25; 80.0%) after stopping NA. A higher pretreatment viral load (≥2000 vs <2000 IU/mL) was associated with increased risks of clinical relapse (hazard ratio, 3.47; 95% confidence interval, 1.56-7.73) and hepatic decompensation (9.91; 2.14-45.92). Of 51 patients with pretreatment viral load <2000 IU/mL, clinical relapse occurred in 10 (19.6 %) and hepatic decompensation in 2 (3.9%). Pretreatment HBV DNA ≥2000 IU/mL is associated with increased risk of liver-related disease after cessation of prophylactic NA therapy in patients who received rituximab-containing chemotherapy.

Ethnicity as predictor of immune reconstitution among Malaysian HIV-positive patients treated with highly active antiretroviral therapy.

The impact of sociodemographic and clinical factors on immune recovery and viral load suppression among HIV-1 positive patients treated with HAART particularly in Malaysia is largely unknown. This cross-sectional study enrolled 170 HIV-1-infected individuals of three major ethnicities who attended three HIV outpatient clinics in Malaysia. Questionnaire was used to obtain sociodemographic data while CD4 count and viral load data were gathered from hospital's record. Multiple factors were assessed for their predictive effects on CD4 count recovery (≥500 cells/mm3 ) and viral load suppression (≤50 copies/mL) using binary logistic regression. Most of the subjects were male (149/87.6%), in the age group 30 to 39 years old (78/45.9%) and got infected via homosexual contact (82/48.2%). Indians were associated with 11 times higher chance for CD4 recovery as compared to Malays at 8 to 12 months of HAART (adjusted OR: 10.948, 95% CI: 1.873, 64.001, P = .008). Viral load suppression was positively influenced by intravenous drug use (IVDU) status (adjusted OR: 35.224, 95% CI: 1.234, 1000.489, P = .037) at 4 to 6 months of HAART. Higher pretreatment CD4 count was a positive predictor for both initial immunological and virological responses while higher pretreatment viral load was a negative predictor for virological suppression only. In conclusion, ethnicity plays a significant role in determining early immune reconstitution in Malaysia, besides pretreatment CD4 count. Further studies are needed to identify possible biological factors underlying this association.

Prevalence and predictors of occult hepatitis C virus infection among Egyptian patients who achieved sustained virologic response to sofosbuvir/daclatasvir therapy: a multi-center study.

BackgroundOccult hepatitis C virus (HCV) infection (OCI) is characterized by the detection of HCV-RNA in non-serum reservoirs, such as peripheral blood mononuclear cells (PBMCs) and/or hepatocytes with undetectable HCV-RNA or antibodies in the serum. In this study, we tried to evaluate the prevalence and possible predictors of OCI in patients who achieved sustained virologic response (SVR) post sofosbuvir/daclatasvir (SOF/DCV) therapy.Patients and methodsA cross-sectional multicenter study was designed to enroll 1,280 HCV-infected patients who received SOF (400 mg) plus DCV (60 mg) once daily ± ribavirin regimen for 12 weeks and achieved SVR 12 weeks post treatment. They were randomly recruited from three dedicated Egyptian centers for management of HCV. Real-time PCR was performed to detect HCV-RNA in serum and PBMCs and to evaluate the different risk factors pertaining to the existence of OCI.ResultsHCV-RNA was detected in PBMCs of 50 (3.9%) of them. All OCI cases exhibited significant fibrosis score and raised pre-treatment alanine aminotransferase (ALT) levels. Logistic regression analysis comparing OCI with non-OCI revealed that high pre-treatment viral load, raised ALT, advanced fibrosis score, prolonged prothrombin time, low albumin, Child B score, antiviral experienced patients, and raised bilirubin are the most significant predictor for the possibility of OCI presence with Odds Ratio as 7.03, 5.13, 4.4, 2.68, 2.52, 1.9, 1.5, and 1.2, respectively.ConclusionIn spite of its remote possibility, OCI post SOF/DCV therapy may be present in some cases, and this may entail a re-auditing for the definition of SVR by dual testing in both serum and PBMCs.

Mortality in a Cohort of HIV-Infected Children: A 12-Month Outcome of Antiretroviral Therapy in Makurdi, Nigeria.

Introduction Recognizing the predictors of mortality among HIV-infected children will allow for concerted management that can reduce HIV-mortality in Nigeria. Methodology A retrospective cohort study in children aged 0–15 years, between October 2010 and December 2013, at the Federal Medical Centre, Makurdi, Nigeria. Kaplan–Meier method analysed the cumulative probability of early mortality (EM) occurring at or before 6 months and after 6 months of follow-up (late mortality-LM) on a 12-month antiretroviral therapy (ART). Multivariate Cox proportional regression models were used to test for hazard ratios (HR). Results 368 children were included in the analysis contributing 81 children per 100 child-years to the 12-month ART follow-up. A significant reduction in EM rates was noted at 17.3 deaths per 100 child-years (30 deaths) to LM rates of 3.0 deaths per 100 child-years (10 deaths), p < 0.01. At multivariate analysis, children with a high pretreatment viral load (≥10,000 copies/ml) were found to be at risk of EM (aHR; 18. 089, 95% CI; 2.428–134.77, p=0.005). Having severe immunosuppression at/or before 6 months of ART was the predictor of LM (aHR; 17.28, 95% CI; 3.844–77.700, p ≤ 0.001). Conclusions Although a lower mortality rate is seen at 12 months of ART in our setting, predictors of HIV mortality are having high pretreatment HIV viral load and severe immunosuppression. While primary prevention of HIV infection is paramount, early identification of these predictors among our HIV-infected children for an early ART initiation can reduce further the mortality in our setting. In addition, measures to ensure a good standard of care and retention in care for a sustained virologic suppression cannot be ignored and are hereby underscored.

Pre-treatment prediction of response to peginterferon plus ribavirin in chronic hepatitis C genotype 3.

To evaluate pre-treatment factors associated with sustained virological response (SVR) in patients with hepatitis C virus (HCV) genotype 3 treated with peginterferon and ribavirin (RBV). We retrospectively analyzed treatment naive, mono-infected HCV genotype 3 patients treated with peginterferon and RBV. Exclusion criteria included presence of other liver disease, alcohol consumption and African American or Asian ethnicity. The variables collected and compared between patients who achieved an SVR and patients who did not were as follows: gender, age, fibrosis stage, diabetes, body mass index, steatosis, INFL3 polymorphism, pre-treatment HCV-RNA, type of peginterferon, RBV dose and adherence. A total of 107 patients treated between June, 2004 and March, 2013 were included. Mean treatment duration was 25.1 (± 1.8) wk. Overall, 58% (62/107) of the patients achieved an SVR and 42% (45/107) did not. In the multivariate logistic regression analysis, pre-treatment HCV-RNA ≥ 600000 UI/mL (OR = 0.375, 95%CI: 0.153-0.919, P = 0.032) and advanced fibrosis (OR = 0.278, 95%CI: 0.113-0.684, P = 0.005) were significantly associated with low SVR rates. In patients with pre-treatment HCV-RNA ≥ 600000 UI/mL and advanced fibrosis, the probability of achieving an SVR was 29% (95%CI: 13.1-45.2). In patients with pre-treatment HCV-RNA < 600000 UI/mL and mild to moderate fibrosis, the probability of achieving an SVR was 81% (95%CI: 68.8-93.4). In patients with HCV genotype 3 infections the presence of advance fibrosis and high pre-treatment viral load might be associated with poor response to peginterferon plus RBV. These patients could benefit the most from new direct antiviral agents-based regimes.

Analysis of variables and interactions among variables associated with a sustained virological response to pegylated interferon alfa-2a plus ribavirin in hepatitis C virus genotype 3-infected patients

The recommended standard therapeutic regimen for chronic hepatitis patients with hepatitis C virus (HCV) genotype 3 is pegylated interferon plus ribavirin for 24 weeks. The aim of the present study was to evaluate treatment efficacy and variables predictive of treatment success, interactions among variables contributing to a response to therapy, and the utility of the rapid virological response (RVR; week 4 virological response) to predict treatment outcomes in HCV genotype 3-infected patients in routine clinical practice. We prospectively studied baseline and during-treatment factors associated with a sustained virological response (SVR) in HCV genotype 3-infected patients who received pegylated interferon alfa-2a (PEG-IFN α2a) 180 μg/week plus ribavirin 800 mg daily for 24 weeks and who were followed for 24 weeks after the completion of treatment. Four hundred and twenty-six treated patients were included in the analysis; 320 (75.1%) showed an SVR. The following factors were assessed for their ability to predict SVR by means of univariable and multivariable logistic regression analysis: patient age, sex, pre-treatment viral load, pre-treatment alanine aminotransferase (ALT), body mass index (BMI), and RVR. Four factors - age, pre-treatment viral load, pre-treatment ALT, and RVR - were statistically significant predictors of SVR (p<0.05) in the univariable analysis. Factors showing a significant association with SVR were assessed by multivariable logistic regression analysis. In the multivariable analysis, independent factors associated with SVR were the attainment of RVR (odds ratio (OR) 11, 95% confidence interval (CI) 6.15-20.69; p<0.0001), patient age ≤40 years (OR 4.2, 95% CI 2.30-7.96, p<0.0001), and a low pre-treatment viral load (≤8 × 10(5) IU/ml; OR 3.4, 95% CI 1.87-6.25; p<0.0001). The effect of RVR in patients aged >40 years was more pronounced than in those aged ≤40 years: 81.1% of patients aged >40 years who achieved an RVR had an SVR, whereas only 7.5% of patients aged >40 years who did not achieve an RVR had an SVR (p<0.05). RVR is an independent variable that is predictive of SVR. Moreover older patients (>40 years) who achieve an RVR are likely to have an SVR, while patients who do not achieve an RVR and who have a high pre-treatment viral load (>8 × 10(5) IU/ml) are unlikely to have an SVR.

Viral Kinetics and Duration of Hepatitis C Therapy

Treatment for hepatitis C is aimed at eliminating the virus and thus preventing the development of cirrhosis. The effectiveness of antiviral therapy with pegylated interferon and ribavirin is based upon inhibition of viral replication and successful viral clearance while maintaining minimal toxicity. Therapy as short as 12 to 16 weeks duration may be adequate for those with genotypes 2 or 3, and 24 weeks may be sufficient for those with genotype 1 and low viral load who achieve rapid virologic response. On the other hand, extension of therapy beyond 48 weeks may be necessary for those with genotype 1 and slow response or those with a high pretreatment viral load who do not achieve rapid virologic response. As new viral kinetic data emerge with pegylated interferon and ribavirin, the tailoring of hepatitis C virus treatment will allow shorter durations of therapy for some patients and a greater chance of sustained response in others who are treated for longer durations.

Impact of Hepatitis B Exposure on Sustained Virological Response Rates of Highly Viremic Chronic Hepatitis C Patients

Aim. To evaluate the impact of hepatitis B core antibody (anti-HBc) seropositivity in sustained virological response (SVR) rates in treatment-naïve, chronic hepatitis C (CHC) patients with high pretreatment viral load (>800000 IU/mL). Methods. 185 consecutive CHC patients (14.4% cirrhotics, 70.2% prior intravenous drug users) treated with pegylated interferon-a2b plus ribavirin, for 24 or 48 weeks based on viral genotype, were retrospectively analyzed. SVR was confirmed by undetectable serum HCV-RNA six months after the end of treatment schedule. Results. Thirty percent of CHC/HBsAg-negative patients were anti-HBc-positive. Anti-HBc positivity was more prevalent in cirrhotic, compared to noncirrhotic patients (76.9% versus 19.5%, P < .05). Serum HBV-DNA was detected in the minority of anti-HBc-positive patients (1.97%). Overall, 62.1% of patients exhibited SVR, while 28.6% did not; 71.4% of non-SVRs were infected with genotype 1. In the univariate analysis, the anti-HBc positivity was negatively associated with treatment outcome (P = .065). In the multivariate model, only the advanced stage of liver disease (P = .015) and genotype-1 HCV infection (P = .003), but not anti-HBc-status (P = .726), proved to be independent predictors of non-SVR. Conclusion. Serum anti-HBc positivity does not affect the SVR rates in treatment-naïve CHC patients with high pretreatment viral load, receiving the currently approved combination treatment.

Patient's age modifies the impact of the proposed predictors of sustained virological response in chronic hepatitis C patients treated with PEG-interferon plus ribavirin

Background The aim of this study was to investigate the effect of patient's age on the impact of typically proposed predictors of sustained virological response (SVR) in treatment-naïve, high-pretreatment viral load (> 700.000 IU/ml), chronic hepatitis C (CHC) patients treated under real-life conditions in Greece. Methods We retrospectively analyzed 185 CHC patients (14.4% cirrhotics) who had been treated with weight-adjusted dosing (1.5 μg/kg per week) of pegylated interferon-a2b (PEG) plus genotype-based ribavirin (RIB) for 24 or 48 weeks of treatment, based on viral genotype. SVR was confirmed by undetectable serum HCV-RNA 6 months after the end of treatment. Results Overall, 68.5% of patients exhibited SVR and 31.5% were non-responders (non-SVRs). Among the non-SVRs, 71.4% were infected with HCV genotype-1. Importantly, 71.4% of genotype 4-infected treated patients exhibited SVR. In the multivariate analyses, only the early histological stage of liver disease ( p = 0.015) and the presence of genotype non-1 infection ( p = 0.003) were independent predictors of SVR. For patients younger than 35 years, none of the baseline parameters and neither viral genotype ( p = 0.284) nor the stage of liver disease ( p = 0.351) was an independent predictor of non-SVR, whereas for patients between 35 and 55, only the presence of genotype-1 infection independently predicted non-SVR ( p = 0.008). For older patients (> 55 years), only the histological stage of liver disease ( p = 0.047) and not the viral genotype ( p = 0.275) independently predicted non-SVR. Conclusions The impact of the typical predictors of SVR, such as viral genotype and liver histopathology, is modified according to patient's age in currently approved combination treatment.

Viral Dynamics and Pharmacokinetics in Combined Interferon Alfa-2b and Ribavirin Therapy for Patients Infected with Hepatitis C Virus of Genotype 1b and High Pretreatment Viral Load

Objective: The aim of this study was to clarify the viral dynamics and single- and multiple-dose pharmacokinetics of ribavirin and interferon (IFN) alfa-2b in the virologic response to combination therapy with both compounds in patients infected with hepatitis C virus (HCV) genotype 1b and high viral load. Methods: Fourteen patients received high-dose daily induction therapy followed by intermittent maintenance therapy with IFN alfa-2b and daily oral ribavirin for 24 weeks, and followed up for 24 weeks after treatment. Single- and multiple-dose pharmacokinetic studies and viral dynamics were assessed by serial measurements of serum concentrations of both compounds and HCV RNA, respectively, at weeks 1 and 24. Results: During treatment, all 14 patients showed biochemical response (i.e., normalization of serum alanine transaminase activity), while 11 showed virologic response (i.e., undetectable serum HCV RNA level by qualitative polymerase chain reaction assay). Sustained biochemical and virologic response after cessation of treatment was noted in 8 and 2 patients, respectively. Serum ribavirin concentrations asymptoted by 4 weeks of treatment. Serum ribavirin concentrations in steady state, and maximum concentration and accumulation rate of ribavirin after multiple dosing were significantly higher in the presence of sustained virologic response. HCV-related parameters were not significantly associated with sustained virologic response. Conclusions: Continuous exposure and tissue accumulation of ribavirin may be necessary for sustained virologic response to combination therapy in chronic hepatitis C with genotype 1b and high viral load. Pharmacokinetic analysis of ribavirin provides information on its mechanism of action and for developing more rational treatment for IFN-resistant HCV.

Emergence of lamivudine resistant HBV is not always associated with HBeAg positive status or a high pretreatment viral load in patients with chronic infection

Emergence of lamivudine resistant HBV is not always associated with HBeAg positive status or a high pretreatment viral load in patients with chronic infection