scholarly journals Pangenotypic and Genotype-Specific Antivirals in the Treatment of HCV Genotype 4 Infected Patients with HCV Monoinfection and HIV/HCV Coinfection

2022 ◽  
Vol 11 (2) ◽  
pp. 389
Author(s):  
Dorota Zarębska-Michaluk ◽  
Jerzy Jaroszewicz ◽  
Anna Parfieniuk-Kowerda ◽  
Małgorzata Pawłowska ◽  
Ewa Janczewska ◽  
...  
Keyword(s):  
Virologic Response ◽  
Hiv Status ◽  
Cure Rate ◽  
Genotype 4 ◽  
Hiv Coinfection ◽  
Significant Difference ◽  
Treatment Naïve ◽  
Hcv Coinfection ◽  
Direct Acting ◽  
Hiv Negative

The introduction of the direct-acting antivirals (DAA) has substantially improved the effectiveness of the therapy in patients with chronic hepatitis C. We aimed to compare the efficacy of pangenotypic and genotype-specific DAA in the cohort of genotype (GT) four patients with HCV monoinfection and HIV coinfection. A total of 662 GT4-infected patients treated in 2015–2020—of whom 168 (25.3%) were coinfected with HIV, selected from the retrospective EpiTer-2 database—were enrolled in the analysis. Among HIV-coinfected patients, 54% (90) were treated with genotype-specific regimens and 46% (78) with pangenotypic options, while among HCV-monoinfected patients, the rates were 72% and 28%, respectively. Significantly higher rate of males (67.9% vs. 57.7%, p = 0.01), a lower rate of liver cirrhosis (10.2% vs. 18.1%, p = 0.02), and higher of treatment-naïve patients (87.5% vs. 76.7%, p = 0.003) were documented in the HIV coinfected population. The overall sustained virologic response after exclusion of non-virologic failures was achieved in 98% with no significant difference between HIV-positive and HIV-negative patients, 96.2% vs. 98.5%, respectively. While the genotype-specific regimens resulted in a similar cure rate regardless of the HIV status, the pangenotypic options were more efficacious in patients with HCV monoinfection (99.3% vs. 94.4%, p = 0.05). Hereby, we demonstrated the high effectiveness and good safety profile of the DAA therapy in the population of HCV GT4 infected patients with HIV coinfection supporting the current recommendations to treat HCV/HIV coinfected patients with the same options as those with HCV monoinfection.

Sustained virologic response and changes in liver fibrosis parameters following 12-wk administration of generic sofosbuvir and daclatasvir in HIV/HCV-coinfected patients with HCV genotype 4 infection

2020 ◽  
Vol 114 (4) ◽  
pp. 232-240
Author(s):  
Ahmed Cordie ◽  
Aisha Elsharkawy ◽  
Shereen Abdel Alem ◽  
Safa Meshaal ◽  
Wafaa El Akel ◽  
...  
Keyword(s):  
Antiviral Agents ◽  
Liver Stiffness ◽  
Virologic Response ◽  
Genotype 4 ◽  
Significant Fibrosis ◽  
Hcv Genotype ◽  
Direct Acting Antiviral ◽  
Significant Difference ◽  
Baseline Variable ◽  
Direct Acting

Abstract Background Novel direct-acting antiviral agents have shown great efficacy and tolerability in HCV-monoinfected patients. However, data are lacking regarding their efficacy and safety in HIV/HCV-genotype (GT) 4-coinfected patients. Methods A single-centre, prospective study including HIV/HCV-GT 4-coinfected patients who were treated with sofosbuvir and daclatasvir (SOF/DCV) was conducted for 12 wk. Sustained virological response (SVR) at week 12 post-treatment (SVR12), adverse events (AEs) and changes in liver stiffness measurement (LSM) at SVR12 in comparison with baseline were evaluated. Results SVR12 was achieved in 46 of 50 patients (92%). No significant difference in SVR12 was noticed among patients who received antiretroviral therapy (ART) regimens compared with those who did not receive ART regimens or between those with insignificant fibrosis (<F2) and those with significant fibrosis (≥F2) (p=0.9 and p=0.3, respectively). AEs occurred in 45 (90%) patients. The most frequent AEs were fatigue, headache and nausea. No treatment-related serious AEs or deaths were reported. HIV control was not compromised. LSM, fibrosis 4 score and aspartate aminotransferase-to-platelet ratio index showed a significant decrease at SVR12 when compared with baseline (p=0.0004, p=0.0003 and p<0.0001, respectively). Logistic regression analysis showed no association between baseline variables and SVR12 while significant fibrosis (≥F2) was the only baseline variable that was significantly associated with improvement of LSM at SVR12. Conclusion SOF/DCV achieved a high SVR12 and was well-tolerated in HIV/HCV-GT 4-coinfected patients.

scholarly journals Treatment of hepatitis C virus infection with direct-acting antiviral agent-based regimens in Iranian patients with hereditary bleeding disorders

2021 ◽  
Vol 18 (1) ◽  
Author(s):  
Heidar Sharafi ◽  
Bita Behnava ◽  
Alireza Azizi-saraji ◽  
Ali Namvar ◽  
Ali Anvar ◽  
...  
Keyword(s):  
Hepatitis C ◽  
Antiviral Agent ◽  
Previous Treatment ◽  
Virologic Response ◽  
Bleeding Disorders ◽  
Hcv Genotype ◽  
Direct Acting Antiviral ◽  
Treatment Naïve ◽  
Hcv Genotype 1 ◽  
Direct Acting

Abstract Background Chronic hepatitis C (CHC) is one of the most important comorbidities in patients with hereditary bleeding disorders (HBD). The present study aimed at evaluating the effectiveness of direct-acting antiviral agent (DAA)-based interferon-free HCV antiviral regimens in patients with HBD. Patients and methods The present study was performed on the patients with HBD and CHC between 2015 and 2019. Sofosbuvir-based interferon-free regimens with or without ribavirin were prescribed to treat HCV infection. The main endpoint of the study was to determine the sustained virologic response (SVR), assessed 12 weeks after the completion of treatment. Results A total of 147 patients with a mean age of 41.1 years were enrolled in the study; 4.1% of them were co-infected with HIV, 25.2% had cirrhosis, and 76.9% of them were diagnosed with hemophilia A. HCV genotype-1 includes the largest number (68.1%) of patients. 46.3% of patients were treatment-naïve and others had a treatment history with interferon-based regimens. Out of 147 patients, 15 patients were lost to follow-up during treatment or for SVR evaluation or discontinued treatment. 132 subjects completed treatment and were evaluated for SVR, 12 weeks after the completion of treatment. All of the patients achieved SVR 12 (SVR rate: 100%, 95% CI 97.2–100%). Conclusion Hepatitis C DAA-based regimens are the effective treatments for CHC in patients with HBD, regardless of the treatment modifiers such as previous treatment experience, cirrhosis, HIV co-infection, and HCV genotype.

scholarly journals Metabolic Changes in Chronic Hepatitis C Patients Who Carry IFNL4-ΔG and Achieve Sustained Virologic Response With Direct-Acting Antiviral Therapy

2019 ◽  
Vol 221 (1) ◽  
pp. 102-109 ◽  
Author(s):  
Benjamin Emmanuel ◽  
Samer S El-Kamary ◽  
Laurence S Magder ◽  
Kristen A Stafford ◽  
Man E Charurat ◽  
...  
Keyword(s):  
Chronic Hepatitis ◽  
Hepatitis C ◽  
Chronic Hepatitis C ◽  
Sustained Virologic Response ◽  
Density Lipoprotein ◽  
Virologic Response ◽  
Direct Acting Antiviral ◽  
Hiv Coinfection ◽  
The Mean ◽  
Direct Acting

Abstract Background Clearance of hepatitis C virus (HCV) results in rapid changes in metabolic parameters early in direct-acting antiviral (DAA) therapy. Long-term changes after sustained virologic response (SVR) remain unknown. Methods We investigated longitudinal changes in metabolic and inflammatory outcomes in chronic hepatitis C (CHC) patients: low-density lipoprotein (LDL), high-density lipoprotein, triglycerides, alanine aminotransferase (ALT), and aspartate aminotransferase (AST) using a general linear model for repeated measurements at 5 clinical time points and by human immunodeficiency virus (HIV) coinfection and IFNL4 genotype. Results The mean LDL increased markedly during DAA therapy (pre-DAA, 86.6 to DAA, 107.4 mg/dL; P < .0001), but then it decreased to 97.7 mg/dL by post-SVR year 1 (P < .001 compared with DAA; P = .0013 compared with SVR). In patients who carry the IFNL4-ΔG allele, mean LDL increased during treatment, then decreased at post-SVR year 1; however, in patients with TT/TT, genotype did not change during and after DAA treatment. The mean ALT and AST normalized rapidly between pre-DAA and DAA, whereas only mean ALT continued to decrease until post-SVR. Metabolic and inflammatory outcomes were similar by HIV-coinfection status. Conclusions Changes in LDL among CHC patients who achieved SVR differed by IFNL4 genotype, which implicates the interferon-λ4 protein in metabolic changes observed in HCV-infected patients.

scholarly journals CIHR Canadian HIV Trials Network Coinfection and Concurrent Diseases Core Research Group: 2016 Updated Canadian HIV/Hepatitis C Adult Guidelines for Management and Treatment

2016 ◽  
Vol 2016 ◽  
pp. 1-34 ◽  
Author(s):  
Mark Hull ◽  
Stephen Shafran ◽  
Alex Wong ◽  
Alice Tseng ◽  
Pierre Giguère ◽  
...  
Keyword(s):  
Hepatitis C ◽  
Pegylated Interferon ◽  
Virologic Response ◽  
National Standards ◽  
Direct Acting Antiviral ◽  
Canadian Context ◽  
Heavy Burden ◽  
Hcv Coinfection ◽  
Direct Acting ◽  
Living With Hiv

Background. Hepatitis C virus (HCV) coinfection occurs in 20–30% of Canadians living with HIV and is responsible for a heavy burden of morbidity and mortality.Purpose. To update national standards for management of HCV-HIV coinfected adults in the Canadian context with evolving evidence for and accessibility of effective and tolerable DAA therapies. The document addresses patient workup and treatment preparation, antiviral recommendations overall and in specific populations, and drug-drug interactions.Methods. A standing working group with HIV-HCV expertise was convened by The Canadian Institute of Health Research HIV Trials Network to review recently published HCV antiviral data and update Canadian HIV-HCV Coinfection Guidelines.Results. The gap in sustained virologic response between HCV monoinfection and HIV-HCV coinfection has been eliminated with newer HCV antiviral regimens. All coinfected individuals should be assessed for interferon-free, Direct Acting Antiviral HCV therapy. Regimens vary in content, duration, and success based largely on genotype. Reimbursement restrictions forcing the use of pegylated interferon is not acceptable if optimal patient care is to be provided.Discussion. Recommendations may not supersede individual clinical judgement. Treatment advances published since December 2015 are not considered in this document.

scholarly journals PD-L1 protein expression and copy number gains in HIV-positive locally advanced cervical cancer

2020 ◽  
Vol 12 ◽  
pp. 175883592096300
Author(s):  
Kongsak Loharamtaweethong ◽  
Napaporn Puripat ◽  
Niphon Praditphol ◽  
Jidapa Thammasiri ◽  
Siriwan Tangitgamol
Keyword(s):  
Cervical Cancer ◽  
Copy Number ◽  
Locally Advanced ◽  
Hiv Positive ◽  
Hiv Status ◽  
Free Survival ◽  
Parametrial Invasion ◽  
Programmed Death ◽  
Significant Difference ◽  
Hiv Negative

Background: The programmed death-1/programmed death-ligand-1 (PD-1/PD-L1) axis may represent a target for cervical cancer; however, it is poorly understood in human immunodeficiency virus (HIV)-infected patients. Methods: We evaluated HIV-positive ( n = 42) and HIV-negative ( n = 110) women with locally advanced cervical cancer regarding their PD-L1 expression, determined by combined positive score (CPS) ⩾ 1 and tumor proportion score (TPS) ⩾ 25%, and PD-L1 copy number alterations, assessed by fluorescence in situ hybridization. Results: Regardless of HIV status, 84.9% and 44.8% of cases were PD-L1-positive according to CPS ⩾ 1 and TPS ⩾ 25%. Per CPS ⩾ 1, PD-L1 positive rate was similar between HIV-positive and HIV-negative women, whereas a significant difference was seen per TPS ⩾ 25%. Tumor size and parametrial invasion were correlated with PD-L1 positivity in HIV-negative women, whereas anti-retroviral therapy (ART) was correlated with TPS < 25%. Low CD4-positive cell counts were associated with CPS < 1 in HIV-positive women. No significant difference was observed in PD-L1 copy number status between HIV-positive and HIV-negative women. PD-L1 amplification and polysomy were independently associated with TPS ⩾ 25%, whereas the presence of parametrial invasion was independently associated with CPS ⩾ 1. Cancer stage and PD-L1 amplification were identified as independent predictors of recurrence-free survival [hazard ratio (HR) = 2.40 (1.32–4.36) and HR = 5.33 (1.94–14.61)] and cancer-specific survival [HR = 13.62 (5.1–36.38) and HR = 3.53 (1.43–8.69)]. PD-L1 polysomy was an independent predictor of locoregional recurrence-free survival [HR = 3.27 (1.27–8.41)]. HIV status and PD-L1 expression (CPS ⩾ 1 or TPS ⩾ 25%) were not associated with poor patient outcomes. Conclusion: PD-L1 amplification and polysomy are the strongest drivers of PD-L1 expression in cervical cancer, and could represent prognostic biomarkers for anti-PD-1/PD-L1 therapy. Cervical cancer biology may be modulated by HIV infection, CD4-positive cells, and HIV treatments.

scholarly journals Liver Damage in Patients with HCV/HIV Coinfection Is Linked to HIV-Related Oxidative Stress

2016 ◽  
Vol 2016 ◽  
pp. 1-11 ◽  
Author(s):  
Xiangbo Huang ◽  
Hua Liang ◽  
Xueying Fan ◽  
Liyan Zhu ◽  
Tao Shen
Keyword(s):  
Oxidative Stress ◽  
Hiv Infection ◽  
Liver Damage ◽  
Central China ◽  
Hiv Positive ◽  
Liver Ultrasound ◽  
Hiv Coinfection ◽  
Chronic Hcv ◽  
Hcv Coinfection ◽  
Hiv Negative

HIV infection aggravates the progression of liver damage in HCV-coinfected patients, with the underlying pathogenesis being multifactorial. Although high level of oxidative stress has been observed frequently in patients infected with HIV or HCV, the status of oxidative stress in HIV/HCV coinfection and its contribution to HCV liver damage have not been determined. This study involved 363 HBsAg-negative, anti-HCV-positive former blood donors recruited from a village in central China in July 2005; of these, 140 were positive for HIV. Of these 363 subjects, 282 were successfully followed up through July 2009. HIV/HCV-coinfected subjects had higher rates of end-stage liver disease-related death than those monoinfected with HCV. Liver ultrasound manifestations were poor in HIV-positive than in HIV-negative individuals, in both chronic HCV carriers and those with resolved HCV. Serum concentrations of total glutathione (tGSH), malondialdehyde (MDA), glutathione peroxidase (GSH-Px), GSSG, and reduced GSH were higher in HIV-positive than HIV-negative subjects. GSSG concentrations were higher in HIV-infected subjects with abnormal ALT/AST levels than in those with normal ALT/AST levels and were associated with poorer liver ultrasound manifestations. These finding indicated that HIV infection accelerated HCV-associated liver damage in HIV/HCV-coinfected individuals. Increased oxidative stress, induced primarily by HIV coinfection, may contribute to aggravated liver damage.

Clinicopathologic Comparison of Plasmablastic Lymphoma Patients According HIV-Status: Peruvian Experience

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 19-19
Author(s):  
Jule F Vasquez ◽  
Cesar Samanez-Figari ◽  
Lourdes Lopez ◽  
Shirley Quintana ◽  
Rolig Aliaga ◽  
...  
Keyword(s):  
Overall Survival ◽  
Hiv Infection ◽  
Lymphoid Cells ◽  
Categorical Variables ◽  
Hiv Positive ◽  
Hiv Status ◽  
Hiv Patients ◽  
Variable Expression ◽  
Significant Difference ◽  
Hiv Negative

Background:Plasmablastic lymphoma (PBL) is an aggressive lymphoma associated mainly to HIV infection, although cases in immunocompetent patients are described as well. Objective:To describe the clinicopathologic features and determine the overall survival of lymphoma patients according human immunodeficiency virus (HIV) status in Peruvian patients. Methods:We reviewed the pathology databases of 2 cancer centers and a general hospital from Peru. Forty cases were documented between 2005 and 2020. Categorical variables were compared using Fisher's exact test. Survival curves were estimated using the Kaplan-Meier method and compared using the log-rank test. Statistical analysis was based on SPSS Program version 23. All cases were reviewed by two pathologists. Results:32 patients (80%) were HIV-positive. The median age for the whole cohort was 40 years (range, 22-86). The median age for HIV-positive and HIV-negative PBL patients were 37 years (range 22-67 years) and 57 years (range 27-86 years), respectively. The proportion of patients ≥60 years was lower in HIV-positive than in HIV-negative patients (8% and 37%, respectively; p= 0.046). 80% of patients in the whole cohort were female, and 84% and 62% in the HIV-positive and HIV-negative group, respectively. Extra-oral primary sites were the most frequent primary sites in both groups (66% and 88%, respectively). There were no statistically significant differences in Ann Arbor stage, Ki-67 expression, LDH levels, IPI scores, albumin levels, and neutrophil/lymphocyte ratio between HIV-positive and HIV-negative patients. All cases showed large lymphoid cells, of plasmablastic morphology with expression of at least one plasma cell marker (CD138, CD38, MUM1), CD45 positivity, variable expression of EMA, CD79 and CD30 and absence of expression of CD20, CD3, CD68 and LMP1; the proliferative index Ki67 varied between 60 and 90%. A small proportion of patients (18%) did not receive chemotherapy because of poor performance status or a personal decision. DA-EPOCH regimen was used in 52% and 25% of HIV+ and HIV- patients, respectively and CHOP/CHOEP regimen in 48 % and 75%, respectively. The overall response rate was 68% and 57% in HIV+ and HIV- patients with complete response (CR) in 32% and 14%, respectively. In the HIV-positive group, 66% of patients were antiretroviral therapy (ART)-naïve. The median progression-free survival (PFS) was 38 months and 7 months for HIV+ and HIV- patients, and the 1-year PFS was 74% and 0%, respectively. The median overall survival (OS) was 43 months (range 0.2-86.5) in HIV-positive patients and 10 months (range 0.5-19.0 months) in HIV-negative patients and the 1-year OS were 59% y 38%, respectively (p=0.27). Conclusions: PBL is a rare lymphoma, specially, if not related to HIV infection. In this study, 60 years or older was the only variable that showed significant difference. In our cohort, HIV-positive patients had better prognosis than HIV-negative PBL patients. Disclosures No relevant conflicts of interest to declare.

Sign in / Sign up

Export Citation Format

Share Document