1. Antiviral kinetics of tenofovir alafenamide and tenofovir disoproxil fumarate over 24 weeks in women of childbearing potential with chronic HBV.
- Author
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Pan CQ, Chang TT, Bae SH, Brunetto M, Seto WK, Coffin CS, Tan SK, Mo S, Flaherty JF, Gaggar A, Nguyen MH, Çelen MK, Thompson A, and Gane EJ
- Subjects
- Adolescent, Adult, Alanine adverse effects, Antiviral Agents adverse effects, Double-Blind Method, Female, Humans, Infectious Disease Transmission, Vertical prevention & control, Middle Aged, Prospective Studies, Tenofovir adverse effects, Treatment Outcome, Viral Load drug effects, Young Adult, Alanine therapeutic use, Antiviral Agents therapeutic use, Hepatitis B virus drug effects, Hepatitis B, Chronic drug therapy, Tenofovir analogs & derivatives, Tenofovir therapeutic use
- Abstract
Background/purpose: Use of tenofovir disoproxil fumarate (TDF) improves patient outcomes in preventing mother-to-child transmission (pMTCT) of the hepatitis B virus (HBV) in mothers with chronic HBV and high viral loads. Given the lack of data for tenofovir alafenamide (TAF) in pMTCT, rates of early viral suppression with TAF and TDF were evaluated in women of childbearing potential (WOCBP) participating in 2 randomized, double-blind, Phase 3 studies in chronic HBV., Methods: In a patient subset meeting WOCBP criteria and with baseline HBV DNA >200,000 IU/mL, rates of viral suppression with TAF or TDF in achieving the target of HBV DNA <200,000 IU/mL at weeks 12 and 24 were assessed. Multivariate logistic regression was used to identify factors predictive of failure to suppress HBV DNA to the target level., Results: In 275 of 1298 (21%) patients meeting WOCBP criteria with high viral load, 93% and 96% had HBV DNA <200,000 IU/mL at weeks 12 and 24, respectively. Results for TAF (n = 194) vs TDF (n = 81) treatment were similar at weeks 12 and 24 (94% vs. 90% and 97% vs. 93%), respectively. High baseline HBV DNA level, genotype D infection, and prior interferon (week 24 only) were predictive of failure to achieve the target level. Both treatments were well tolerated with TAF showing less impact on renal and bone parameters., Conclusions: In WOCBP with high VL, no differences were found between TAF and TDF in reducing HBV DNA to levels associated with lower transmission risk. These data support ongoing studies of TAF for pMTCT., Competing Interests: Calvin Pan has received research grants from Gilead Sciences (Gilead) and Merck. He also serves as a consultant or advisor for Gilead, and speakers’ bureau for Gilead, Abbvie, and Intercept. Ting-Tsung Chang and Si Hyun Bae declare no conflicts of interest. Wai Kay Seto serves on the advisory boards of Gilead, Abbvie and CSL Behring, and is a speaker for Gilead, AbbVie and Mylan. Maurizia Brunetto has received research grants from AbbVie, BMS, MSD, has served on advisory Boards for AbbVie, Gilead, Janssen; Roche, and has served as a speaker for AbbVie, Gilead, MSD. Carla S. Coffin has served as an investigator or received research grants from GlaxoSmithKline, Gilead, Arbutus Biopharma, Bristol-Myers Squibb, has received educational grants from Merck, Gilead, Janssen, has served on advisory boards for Merck, Gilead, GlaxoSmithKline, has served on Clinical Trial and Publication Committee for Spring Bank Pharmaceuticals, and has participated as a primary investigator in clinical trials for Gilead, Spring Bank, Transgene, and Janssen. The following authors are employees of Gilead Sciences and hold stock interest in the company: Susanna Tan, Shuyuan Mo, John Flaherty, and Anuj Gaggar. Mindie H. Nguyen has received research support from Gilead and Pfizer, has served on advisory boards and/or as a consultant for Novartis, Spring Bank, Janssen, Gilead, Eisai, Bayer. Exact Science, and LAM. Mustafa Kemal Çelen has no conflicts of interest to disclose. Alexander Thompson has received research support from Gilead, AbbVie, and Merck, and has served on advisory boards and/or as a consultant for Gilead, AbbVie, Merck, BMS, Eisai. Edward J. Gane has served as a consultant or advisor for Gilead, AbbVie, Roche, Janssen and at speakers’ bureaus for Gilead and AbbVie. This does not alter our adherence to PLOS ONE policies on sharing data and materials.
- Published
- 2021
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