Evolution of Estimated Glomerular Filtration Rate in Human Immunodeficiency Virus and Hepatitis C Virus-coinfected Patients Receiving Sofosbuvir-based Direct-acting Antivirals and Antiretroviral Therapy

Chen-Hua Liu; Hsin-Yun Sun; Szu-Min Hsieh; Wen-Chun Liu; Wang-Hui Sheng; Chun-Jen Liu; Tung-Hung Su; Tai-Chung Tseng; Pei-Jer Chen; Chien-Ching Hung; Jia-Horng Kao

Disclosures

J Viral Hepat. 2021;28(6):887-896. 

In This Article

Materials and Methods

Patients

Between March 2016 and May 2020, HIV/HCV-coinfected patients aged 20 years or more who had received ART for ≥6 months prior to the initiation of DAAs for chronic HCV infection were prospectively recruited at the National Taiwan University Hospital (NTUH) and NTUH Yun-Lin Branch. The ART and DAA regimens of each patient were determined based on the physicians' discretion. Chronic HCV infection was defined as the presence of detectable HCV antibody (anti-HCV; Abbott HCV EIA 2.0, Abbott Laboratories) and detectable serum HCV RNA level (Cobas TaqMan HCV Test v2.0, Roche Diagnostics GmbH, lower limit of quantification [LLOQ]: 15 IU/ml) for ≥6 months. Patients were excluded from the study if they had decompensated cirrhosis, chronic kidney disease (CKD) stage 5 with eGFR <15 ml/min/1.73 m2, active HCC or organ transplantation, hepatitis B virus (HBV) coinfection which was defined as the presence of serum HBV surface antigen (HBsAg) (Abbott Architect HBsAg qualitative assay, Abbott Laboratories), received non-SOF-based DAAs, or if they refused to provide informed consent. Patients who switched ART regimen during the study period were excluded from the analysis. The study was approved by the NTUH Research Ethics Committee and was conducted in accordance with the principles of Declaration of Helsinki. All patients provided informed consent before participating in the study. Data that support the findings of this study are available from the corresponding author upon reasonable request.

Study Design

Baseline participants' characteristics, including age, sex, history of diabetes mellitus (DM), arterial hypertension (HTN), body mass index (BMI), types of ART regimen for HIV and DAA regimen for HCV, and information regarding acquired immunodeficiency syndrome (AIDS) which was defined as a CD4 T cell count <200 × 106 cells/L or documenting an AIDS-defining complication at the time of HIV diagnosis, were collected. Hemogram, international normalized ratio (INR), serum albumin, total bilirubin, aspartate aminotransferase (AST), alanine aminotransferase (ALT), creatinine, fasting glucose, anti-HCV, HBsAg, HCV RNA, HCV genotype (Abbott RealTime HCV Genotype II, Abbott Laboratories) and HIV RNA (Cobas Taqman HIV-1 Test v2.0, Roche Diagnostics GmbH, lower limit of quantification [LLOQ]: 20 copies/ml) were assessed.[23] The stage of hepatic fibrosis was determined by liver stiffness measurement (LSM, FibroScan®, Echosens).[24]

The eGFR was assessed by the CKD Epidemiology Collaboration (CKD-EPI) equation for all eligible patients at the following time points: baseline, on-treatment weeks 1, 2, 4, 6, 8 and 12, and off-treatment weeks 4, 8, and 12 for SOF-based DAA therapy.[25]

Statistical Analysis

We used the Statistical Program for Social Sciences (SPSS Statistics version 23.0, IBM Corp.) for all statistical analyses. The baseline characteristics for different participant groups are shown by mean (standard deviation, SD) and percentages, and compared by the independent two-sample t-test and chi-squared with Fisher's exact test, respectively. The eGFR evolution is presented from baseline to the off-treatment week 12 (SVR12) by slope coefficient (ml/min/1.73 m2/month). By generalized estimated equation (GEE), we showed the differences of the crude slope coefficient with 95% confidence interval (CI) for age, sex, BMI, DM, HTN, hepatic fibrosis stage, fasting glucose, HCV viral load, HCV genotype, CKD stage, and ART regimen.[26] Factors with a p value <0.10 by crude analysis were put into the adjusted analysis to find independent factors associated with the differences of eGFR evolution. Furthermore, we did subgroup analysis for trends of eGFR evolution among participants on TDF-based and TAF-based ART. The severity of eGFR changes between the time points of baseline and on-treatment week 12, and between the time points of baseline and SVR12 in participants receiving TFV-based and TFV-free ART was graded as > −50%, −50% to −30%, −30% to −10%, −10% to 10%, 10% to 30%, 30% to 50%, and >50%, according to the Division of AIDS (DAIDS) Table for Grading the Severity of Adult and Pediatric Adverse Event.[27] The mean percentage and grade of eGFR changes between participants on TFV-based and TFV-free ART were compared by the independent two-sample t-test and chi-squared with Fisher's exact test, respectively. All statistics were two-tailed, and the results were considered statistically significant when a p value was <0.05.

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