Efficacy and Safety of Elvitegravir/Cobicistat/Emtricitabine/Tenofovir Alafenamide as Maintenance Treatment in HIV/HBV-coinfected Patients

Yu-Shan Huang, MD; Chien-Yu Cheng, MD; Bo-Huang Liou, MD; Po-Liang Lu, MD, PhD; Shu-Hsing Cheng, MD, PhD; Yuan-Ti Lee, MD; Chun-Eng Liu, MD; Hsin-Yun Sun, MD; Chia-Jui Yang, MD; Hung-Jen Tang, MD; Shih-Ping Lin, MD; Mao-Wang Ho, MD; Sung-Hsi Huang, MD; Hung-Chin Tsai, MD, PhD; Chen-Hsiang Lee, MD; Chien-Ching Hung, MD, PhD

Disclosures

J Acquir Immune Defic Syndr. 2021;86(4):473-481. 

In This Article

Methods

Study Design and Participants

This prospective, observational cohort study was conducted at 13 hospitals designated for HIV care around Taiwan. From February to October 2018, HIV/HBV-coinfected adults (aged ≥20 years) who were switched from TDF/FTC or TDF plus 3TC-based regimens to coformulated E/C/F/TAF as maintenance treatment were enrolled. The inclusion criteria included the use of TDF/FTC or TDF plus 3TC as backbone plus a third agent for 6 months or longer; plasma HIV RNA <50 copies/mL twice over the past 12 months; no known resistance mutations to integrase strand transfer inhibitors (InSTIs); no previous history of HIV treatment failure while receiving InSTI-containing ART; no known resistance mutations to TDF, FTC, or 3TC; no previous history of HIV treatment failure while receiving TDF, FTC, or 3TC-containing ART; estimated glomerular filtration rate (eGFR) ≥30 min/mL (calculated by the CKD-EPI equation); and aspartate aminotransferase and alanine aminotransferase (ALT) lower than 2-fold the upper limit of normal. The patients were excluded if they had the following conditions: active opportunistic illness, on treatment of tuberculosis, pregnancy or lactation, hepatic decompensation (Child-Pugh class C), allergy to TDF, TAF, FTC, 3TC, or InSTIs, intolerance of InSTIs, HCV coinfection with treatment with direct-acting antiviral agents or interferon/ribavirin planned within 48 weeks, and concurrent use of medications that were contraindicated with E/C/F/TAF. All included patients were followed for 48 weeks.

Our primary end points were the proportions of participants who failed to achieve undetectable plasma HBV DNA (<20 IU/mL) and plasma HIV RNA (<50 copies/mL) at week 48 after switching to E/C/F/TAF. The secondary end points included the proportions of undetectable plasma HBV DNA (<20 IU/mL) and plasma HIV RNA (<50 copies/mL), the serologic response of HBV to E/C/F/TAF, and the interval changes of eGFR, proteinuria, and BMD.

Ethics Statement

The study was approved by the research ethics committee or institutional review boards of the 13 participating hospitals (registration number: 201710056RINB, 107025-F, TYGH107001, 18MMHIS012e, CMUH107-REC2-081, 107-005-E, CS18052, CF18037B, 171203, 10701-008, 201701662A3, KMUHIRB-SV(II)-20170065, and VGHKS18-CT1-18). All participants gave written informed consent before enrollment. The study was registered with ClinicalTrials.gov (NCT03425994).

Data Collection and Definitions

A standardized case record form was used to collect the information on the demographics, sexual preference, weight at enrollment, comorbidity, concomitant medications, treatment history of HIV and HBV, and the results of laboratory investigations. Tests for plasma HIV RNA, CD4 lymphocyte count, rapid plasma reagin titer, serum creatinine, liver function, lipid profile, and fasting blood glucose or glycated hemoglobin (HbA1C) were performed every 3–6 months by following the national HIV treatment guidelines in Taiwan. For HBV coinfection, plasma HBV DNA, HBsAg, anti-HBs, HBeAg, anti-HBe, and anti-HDV IgG were tested at a central laboratory at baseline and every 24 weeks after switching to E/C/F/TAF. For patients with a positive anti-HDV IgG, HDV RNA was determined. Abdominal sonography and assessments of eGFR, urine sediment, urine protein–creatinine ratio, urine albumin–creatinine ratio (UACR), and urine β2-microglobulin–creatinine ratio were performed at baseline and weeks 24 and 48. BMDs were measured at baseline and 24 and 48 weeks after switching to E/C/F/TAF.

Chronic HBV infection was defined as the persistence of HBsAg for >6 months.[22] HIV treatment failure was defined as a plasma HIV RNA >400 copies/mL.[23] Undetectable plasma HBV and HIV were defined as <20 IU/mL and <50 copies/mL, respectively. The upper limit of normal for the serum ALT level was 40 IU/mL.

Laboratory Investigations

Plasma HBV DNA was quantified using the COBAS AmpliPrep/COBAS TaqMan HBV test (version 2.0, Roche Molecular Systems, Inc., Pleasanton, CA). The HBV serological markers (HBsAg, anti-HBs antibody, HBeAg, and anti-HBe antibody) were determined using the chemiluminescent microparticle immunoassay (Abbott Laboratories, Abbott Park, IL). HDV RNA was quantified using the previously described method,[24] and anti-HDV IgG was determined by competitive enzyme immunoassay according to the manufacturer's instructions (Dia.Pro Diagnostic BioProbes Srl, Milan, Italy). The urine protein, urine albumin, and urine β2-microglobulin were also quantified (Angene Biotechnology Co., Ltd., Taiwan).

BMD Measurement

BMD assessment was performed in 181 participants enrolled at 4 participating hospitals. BMD of the lumbar spine (L1-L4) and total hip were assessed using dual energy x-ray absorptiometry (Lunar Prodigy; GE Healthcare, Machelen, Belgium). According to the WHO criteria, osteopenia is defined as a BMD T-score between −1.0 and −2.5, and osteoporosis is defined as a BMD T-score less than or equal to −2.5.[25] WHO recommends using Z-scores in reporting BMD for premenopausal women or men younger than 50 years, and a Z-score of −2.0 or lower is defined as low BMD for chronological age.[26]

Statistical Analysis

The distributions of participants' demographics and baseline characteristics were presented with descriptive statistics. Categorical variables were compared using the χ 2 test or Fisher exact test, and continuous variables using the Mann–Whitney U test. For paired data, categorical variables were compared using the McNemar test, and continuous variables using the Wilcoxon signed-rank test. Measurements of plasma HBV DNA at each time point were analyzed using generalized estimating equations for repeated measurements in the longitudinal follow-up. A linear regression model was applied to test the association between changes in weight and lipids. All P values were 2 sided, and a P value <0.05 was considered statistically significant. Statistical analyses were performed using SPSS software version 25.0 (SPSS Inc., Chicago, IL).

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