scholarly journals Discordant Liver Fibrosis Predictors in Virologically Suppressed People Living with HIV without Hepatitis Virus Infection

Diagnostics ◽  
2021 ◽  
Vol 12 (1) ◽  
pp. 14
Author(s):  
Barbara Rossetti ◽  
Valentina Borgo ◽  
Arianna Emiliozzi ◽  
Marta Colaneri ◽  
Giacomo Zanelli ◽  
...  
Keyword(s):  
Liver Fibrosis ◽  
Virus Infection ◽  
Viral Hepatitis ◽  
Hepatitis Virus ◽  
People Living With Hiv ◽  
Non Invasive ◽  
Tenofovir Alafenamide ◽  
Living With Hiv ◽  
Hepatitis Virus Infection ◽  
Hiv 1

Severe liver fibrosis (LF) is associated with poor long-term liver-related outcomes in people living with HIV (PLWH). The study aimed to explore the prevalence and predictors of LF and the concordance between different non-invasive methods for the estimation of LF in HIV-infected individuals without hepatitis virus infection. We enrolled PLWH with HIV-1-RNA <50 copies/mL for >12 months, excluding individuals with viral hepatitis. LF was assessed by transient elastography (TE) (significant >6.65 kPa), fibrosis-4 (FIB-4) (significant >2.67), and AST-to-platelet ratio index (APRI) (significant >1.5). We included 234 individuals (67% males, median age 49 years, median time from HIV diagnosis 11 years, 38% treated with integrase strand transfer inhibitors). In terms of the TE, 13% had ≥F2 stage; FIB-4 score was >1.5 in 7%; and APRI > 0.5 in 4%. Higher body mass index, diabetes mellitus, detectable baseline HIV-1 RNA and longer atazanavir exposure were associated with higher liver stiffness as per TE. Predictors of higher APRI score were CDC C stage and longer exposure to tenofovir alafenamide, while HBcAb positivity and longer exposure to tenofovir alafenamide were associated to higher FIB-4 scores. Qualitative agreement was poor between FIB-4/TE and between APRI/TE by non-parametric Spearman correlation and kappa statistic. In our study, in the group of PLWH without viral hepatitis, different non-invasive methods were discordant in predicting liver fibrosis.

scholarly journals A PREDICTIVE MODEL FOR NON-INVASIVE EVALUATION OF LIVER FIBROSIS IN PATIENTS WITH CHRONIC HEPATITIS VIRUS INFECTION

2014 ◽  
Vol 10 (4-5) ◽  
pp. 405
Author(s):  
A. A. Ostanin ◽  
E. L. Gelfgadt ◽  
M. V. Shipunov ◽  
E. Ya. Shevela ◽  
E. V. Kurganova ◽  
...  
Keyword(s):  
Chronic Hepatitis ◽  
Liver Fibrosis ◽  
Virus Infection ◽  
Predictive Model ◽  
Hepatitis Virus ◽  
Non Invasive ◽  
Hepatitis Virus Infection ◽  
Invasive Evaluation

scholarly journals Dynamics of the Decay of Human Immunodeficiency Virus (HIV) RNA and Distribution of Bictegravir in the Genital Tract and Rectum in Antiretroviral-naive Adults Living With HIV–1 Treated With Bictegravir/Emtricitabine/Tenofovir Alafenamide (Spanish HIV/AIDS Research Network, PreEC/RIS 58)

2020 ◽  
Author(s):  
Arkaitz Imaz ◽  
Juan M Tiraboschi ◽  
Jordi Niubó ◽  
Javier Martinez-Picado ◽  
Mackenzie L Cottrell ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Research Network ◽  
People Living With Hiv ◽  
Limit Of Quantification ◽  
Immunodeficiency Virus ◽  
Liquid Chromatography Tandem Mass ◽  
Half Maximal Effective Concentration ◽  
Tenofovir Alafenamide ◽  
Living With Hiv ◽  
Hiv 1

Abstract Background The pharmacokinetics of bictegravir (BIC) and its association with the decay of human immunodeficiency virus (HIV)–1 RNA in genital fluids and the rectum have not yet been addressed. Methods We conducted a prospective, multicenter study of antiretroviral-naive people living with HIV-1 and initiating BIC/emtricitabine (FTC)/tenofovir alafenamide (TAF). HIV-1 RNA was measured (limit of quantification, 40 copies/mL) in blood plasma (BP), seminal plasma (SP), rectal fluid (RF), and cervicovaginal fluid (CVF) at baseline; Days 3, 7, 14, and 28; and Weeks 12 and 24. Total and protein-unbound BIC concentrations at 24 hours postdose (C24h) were quantified in BP, SP, CVF and rectal tissue (RT) on Day 28 and Week 12 using a validated liquid chromatography-tandem mass spectrometry assay. Results The study population comprised 15 males and 8 females. In SP, RF, and CVF, the baseline HIV-1 RNA was &gt;40 copies/mL in 12/15, 13/15, and 4/8 individuals, respectively, with medians of 3.54 (2.41–3.79), 4.19 (2.98–4.70), and 2.56 (1.61–3.56) log10 copies/mL, respectively. The initial decay slope was significantly lower in SP than in RF and BP. The time to undetectable HIV-1 RNA was significantly shorter in SP and RF than in BP. All women achieved undetectable HIV-1 RNA in CVF at Day 14. The median total BIC concentrations in SP, RT, and CVF were 65.5 (20.1–923) ng/mL, 74.1 (6.0–478.5) ng/g, and 61.6 (14.4–1760.2) ng/mL, respectively, representing 2.7%, 2.6%, and 2.8% of the BP concentration, respectively, while the protein-unbound fractions were 51.1%, 44.6%, and 42.6%, respectively. Conclusions BIC/FTC/TAF led to rapid decay of HIV-1 RNA in genital and rectal fluids. Protein-unbound BIC concentrations in SP, RT, and CVF highly exceeded the half-maximal effective concentration (EC50) value (1.1 ng/mL). Clinical Trials Registration EudraCT 2018-002310-12.

Cerebrospinal fluid exposure to bictegravir/emtricitabine/tenofovir in HIV-1-infected patients with CNS impairment

2021 ◽  
Author(s):  
Thibaut Gelé ◽  
Antoine Chéret ◽  
Alicia Castro Gordon ◽  
Lionelle Nkam ◽  
Valérie Furlan ◽  
...  
Keyword(s):  
Real Life ◽  
Antiretroviral Drugs ◽  
People Living With Hiv ◽  
Hiv Cure ◽  
Crucial Component ◽  
Total Plasma Concentration ◽  
Tenofovir Alafenamide ◽  
Living With Hiv ◽  
Csf Concentration ◽  
Hiv 1

Abstract Objectives The penetration of antiretroviral drugs into deep compartments, such as the CNS, is a crucial component of strategies towards an HIV cure. This study aimed to determine CSF concentrations of bictegravir, emtricitabine and tenofovir in patients with HIV-related CNS impairment (HCI) enrolled in a real-life observational study. Methods Patients with HCI treated by optimized ART, including bictegravir/emtricitabine/tenofovir alafenamide (BIC/FTC/TAF) for at least 1 month were enrolled. Plasma and CSF concentrations were measured by quality control-validated assays (LC-MS/MS). The inhibitory quotient (IQARV) was calculated as the ratio of unbound (bictegravir) or total (emtricitabine and tenofovir) concentration to half (or 90%) maximal inhibitory concentration for bictegravir (or emtricitabine and tenofovir). All numerical variables are expressed as median (range). Results Twenty-four patients (nine women) were enrolled. The age was 45 (26–68) years. Unbound bictegravir and total emtricitabine and tenofovir CSF concentrations were 4.4 (1.6–9.6), 84.4 (28.6–337.4) and 1.6 (0.7–4.3) ng/mL, respectively. The unbound bictegravir CSF fraction was 34% (15%–82%) versus 0.33% (0.11%–0.92%) in plasma. Three patients had an IQARV above unity for the three antiretrovirals. Factors positively associated with the CSF concentration (unbound for bictegravir) were age and total plasma concentration for the three antiretrovirals. Patients aged over 51 years had higher CSF concentrations (unbound for bictegravir). Conclusions We observed low CSF exposure to bictegravir, emtricitabine and tenofovir. These results suggest that BIC/FTC/TAF should be used with caution as first-line treatment for people living with HIV with HCI under 51 years of age.

Kidney Cancer Linked to Chronic Hepatitis in the Asia-Pacific: A Population-Based Analysis

2016 ◽  
Vol 45 (1) ◽  
pp. 22-31 ◽  
Author(s):  
Yu-Shan Lin ◽  
Chih-Ching Yeh ◽  
Yen-Chung Lin ◽  
Chien-Tien Su ◽  
Fung-Chang Sung ◽  
...  
Keyword(s):  
Chronic Hepatitis ◽  
Virus Infection ◽  
Viral Hepatitis ◽  
Renal Cancer ◽  
Hepatitis Virus ◽  
Population Based ◽  
Hcv Infection ◽  
Asia Pacific ◽  
Hepatitis Infection ◽  
Hepatitis Virus Infection

Background: The association of renal cancer with viral hepatitis infection remains unclear. Using an insurance data set, this population-based case-control study evaluated the association of renal cancer with chronic hepatitis virus infection in an endemic area of hepatitis B virus (HBV) and hepatitis C virus (HCV) infection. Methods: We enrolled 17,747 patients with renal cancer during the period from 2000 to 2011 from the National Health Insurance Research Database of Taiwan. The control group comprised 35,494 randomly selected people without renal cancer matched by age and gender to the patients in the study group. ORs were calculated to assess the association of chronic hepatitis virus infection with renal cancer by using logistic regression analysis. Results: Renal cancer was associated with HBV and HCV infection (OR 1.38, 95% CI 1.24-1.54; OR 1.24, 95% CI 1.07-1.44, respectively). An analysis stratified by gender and age revealed that young male HBV carriers had a higher risk of renal cancer compared with men without viral hepatitis (age <55 years: OR 1.94, 95% CI 1.57-2.39; 55≤ age <64 years: OR 1.40, 95% CI 1.05-1.86). Male HCV-infected patients aged <55 years (OR 1.90, 95% CI 1.11-3.26) and female HCV carriers aged between 55 and 64 years (OR 1.59, 95% CI 1.00-2.53) had a significantly higher risk of renal cancer compared with their counterparts. Conclusions: Renal cancer is significantly associated with chronic hepatitis infection, particularly in younger HBV-infected men.

scholarly journals A Bioinformatic Analysis of Correlations between Polymeric Immunoglobulin Receptor (PIGR) and Liver Fibrosis Progression

2021 ◽  
Vol 2021 ◽  
pp. 1-12
Author(s):  
Yuan Zhang ◽  
Wenjun Lu ◽  
Xiaorong Chen ◽  
Yajuan Cao ◽  
Zongguo Yang
Keyword(s):  
Liver Fibrosis ◽  
Virus Infection ◽  
Predictive Value ◽  
Hepatitis Virus ◽  
Enrichment Analysis ◽  
Normal Liver ◽  
Fibrosis Stage ◽  
Polymeric Immunoglobulin Receptor ◽  
Immunoglobulin Receptor ◽  
Hepatitis Virus Infection

Objective. This study is aimed at investigating the enriched functions of polymeric immunoglobulin receptor (PIGR) and its correlations with liver fibrosis stage. Methods. PIGR mRNA expression in normal liver, liver fibrosis, hepatic stellate cells (HSCs), and hepatitis virus infection samples was calculated in Gene Expression Omnibus (GEO) and Oncomine databases. Enrichment analysis of PIGR-related genes was conducted in Metascape and Gene Set Enrichment Analysis (GSEA). Logistic model and ROC curve were performed to evaluate the correlations between pIgR and liver fibrosis. Results. PIGR mRNA was upregulated in advanced liver fibrosis, cirrhosis compared to normal liver (all p < 0.05 ). PIGR mRNA was also overexpressed in activated HSCs compared to senescent HSCs, liver stem/progenitor cells, and reverted HSCs (all p < 0.05 ). Enrichment analysis revealed that PIGR-related genes involved in the defense response to virus and interferon (IFN) signaling. In GEO series, PIGR mRNA was also upregulated by hepatitis virus B, C, D, and E infection (all p < 0.05 ). After adjusting age and gender, multivariate logistic regression models revealed that high PIGR in the liver was a risk factor for liver fibrosis ( OR = 82.2 , p < 0.001 ). The area under curve (AUC), positive predictive value (PPV), negative predictive value (NPV), sensitivity, and specificity of PIGR for liver fibrosis stage >2 were 0.84, 0.86, 0.7, 0.61, and 0.90. Conclusion. PIGR was correlated with liver fibrosis and might involve in hepatitis virus infection and HSC transdifferentiation.

scholarly journals Switching to a Bictegravir Single Tablet Regimen in Elderly People Living with HIV-1: Data Analysis from the BICTEL Cohort

Diagnostics ◽  
2021 ◽  
Vol 12 (1) ◽  
pp. 76
Author(s):  
Alessandro Lazzaro ◽  
Elio Gentilini Cacciola ◽  
Cristian Borrazzo ◽  
Giuseppe Pietro Innocenti ◽  
Eugenio Nelson Cavallari ◽  
...  
Keyword(s):  
T Cells ◽  
Real Life ◽  
Total Body Weight ◽  
P Value ◽  
People Living With Hiv ◽  
Single Tablet Regimen ◽  
Total Body ◽  
Tenofovir Alafenamide ◽  
Living With Hiv ◽  
Hiv 1

Bictegravir/emtricitabine/tenofovir alafenamide fumarate (BIC/FTC/TAF) is a recommended once-daily single tablet regimen for the treatment of people living with HIV-1 (PLWH). We aimed to assess efficacy, safety and tolerability of BIC/FTC/TAF among PLWH, with a specific focus on people older than 55 years. Thus, we recruited an observational retrospective real-life cohort including all PLWH who underwent a therapeutic switch to BIC/FTC/TAF, independently from the provenience treatment regimen. After 48 weeks of follow-up, 147 PLWH were included and 93 were older than 55 years. PLWH with HIV-RNA < 37 copies/mL increased from 140 to 146 (p < 0.033). Among the overall population, we observed an increase in CD4+ T cells count by 30.1% (p-value < 0.001), in CD8+ T cells count by 7.1% (p-value = 0.004) and in CD4+/CD8+ ratio by 21.5% (p-value < 0.001). Lipidic profile was characterized by decreasing total cholesterol/HDL ratio by 8% (p-value < 0.001) and LDL by 6.8% (p-value = 0.007). Total body weight increased by 1.8% (p-value = 0.014) and BMI by 4.2% (p-value < 0.001), even remaining within the healthy range. Hepatic and renal profile were not altered by the switch, nor were adverse events and/or discontinuations events detected. In conclusion, BIC/FTC/TAF is effective, safe and well tolerated in real life and among PLWH older than 55.

scholarly journals Protocol for a phase IV, open-label feasibility study investigating non-invasive markers of hepatic fibrosis in people living with HIV-1 and non-alcoholic fatty liver disease randomised to receiving optimised background therapy (OBT) plus maraviroc or OBT alone

BMJ Open ◽  
2020 ◽  
Vol 10 (7) ◽  
pp. e035596
Author(s):  
Daniel Bradshaw ◽  
Yvonne Gilleece ◽  
Sumita Verma ◽  
Iga Abramowicz ◽  
Stephen Bremner ◽  
...  
Keyword(s):  
Hepatic Fibrosis ◽  
People Living With Hiv ◽  
Open Label ◽  
Alcoholic Fatty Liver ◽  
Non Invasive ◽  
Background Therapy ◽  
Secondary Outcomes ◽  
Living With Hiv ◽  
Alcoholic Fatty Liver Disease ◽  
Hiv 1

IntroductionAt least 30% of people living with HIV (PLWH) infection have non-alcoholic fatty liver disease (NAFLD), which has now become a leading cause of hepatic fibrosis and cirrhosis. Management is based largely on lifestyle modifications, which are difficult to achieve, and therapeutic options are urgently needed. Maraviroc (MVC), through antagonism of CCR5 receptors, may reduce hepatic fibrosis progression and could be an effective treatment for NAFLD. However, dosing is usually two times per day, unlike most currently recommended antiretroviral therapies. This study will investigate the feasibility and acceptability of addition of MVC to combination antiretroviral therapy in PLWH and NAFLD as a treatment for NAFLD.Methods and analysisThis is a phase IV, randomised, open-label, non-invasive feasibility study. Sixty individuals with well-controlled HIV-1 and NAFLD will be recruited from UK HIV clinics and randomised 1:1 to receive either optimised background therapy (OBT) plus MVC or OBT alone. Follow-up will be every 24 weeks for 96 weeks. The primary outcome measures will include recruitment and retention rates, adverse events and adherence. Secondary outcomes will include changes in markers of hepatic fibrosis, including the Enhanced Liver Fibrosis score, median liver stiffness measurement and controlled attenuation parameter scores on Fibroscan, and quality of life assessments. Analyses will be performed according to intention-to-treat principles. For secondary outcomes, estimated differences and 95% CIs between the groups using a t-method will be presented for continuous variables and as exact 95% binomial CIs for categorical variables.Ethics and disseminationEthical approval was obtained through the London Dulwich UK Research Ethics Committee (reference 17/LO/2093). Results will be disseminated both through community groups and peer-reviewed scientific literature.Trial registration number SRCTN31461655. EudraCT number 2017-004141-24; Pre-results.

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