Efficacy and Safety of Tenofovir Disoproxil Treatment for Chronic Hepatitis B Patients with Genotypic Resistance to Other Nucleoside Analogues

Abstract

Background:Tenofovir disoproxil (TDF) is a promising salvage therapy for patients with chronic hepatitis B (CHB) who failed regimens of other nucleoside analogues (NAs). In this study, we aimed to investigate the clinical efficacy and safety of TDF monotherapy in Chinese CHB patients with genotypic resistance.Methods:A total of 33 CHB patients who had failed treatment with other NAs and had genotypic resistance were switched to TDF monotherapy for 48 weeks. Patients’ demographic data (age, sex, history of hepatitis B virus [HBV] therapy), laboratory testing results (hepatitis B e antigen [HBeAg] status, HBV DNA levels, alanine aminotransferase [ALT] levels, serum creatinine, urinary protein, genotypic assay), clinical symptoms, and liver color ultrasound examinations were collected for evaluation at day 0 (baseline) and the 12th, 24th, 36th, and 48th weeks after initiating treatment. Statistical analyses were carried out using rank sum test or rank correlation.Results:With regard to efficacy, the study found that all patients who switched to TDF monotherapy had undetectable HBV DNA levels after 48 weeks. In addition, patients with lower baseline HBV DNA levels realized earlier virological undetectability (rs = 0.39, P = 0.030). ALT levels were normal in 30 of 33 patients (91%). HBeAg negative conversion occurred in 7 of 25 patients (28%), among whom HBeAg seroconversion (12%) and HBeAg seroclearance (16%) occurred. The time of complete virological response was significantly affected by the number of resistance loci (rs = 0.36, P = 0.040). Concerning safety, the study found that no adverse events were observed during the 48 weeks.Conclusion:TDF monotherapy is an effective and safe salvage treatment for CHB patients who are resistant to other NAs.

Lipid profile and renal safety of tenofovir disoproxil fumarate-based anti-retroviral therapy in HIV-infected Chinese patients

“…TDF-based ART can effectively restore the immune function of PLWH as reflected by the rapid increase in CD4 + T cell count in the first 12 weeks of ART and the slow increase in CD4 + T cell count afterwards. These results also have been supported by other studies (Wu et al, 2016;Gazzard et al, 2014;Zhou et al, 2017;Amiel et al, 2014). Compared with other regimens, TDF-based regimens showed no difference in the gain of CD4 + T cell count (Hemkens et al, 2015).…”

“…Many studies have demonstrated that ART can lead to a significantly increased prevalence of dyslipidemia (Wu et al, 2016;Zhou et al, 2017;Huang et al, 2015a;Molina et al, 2008;Ortiz et al, 2008), and HIV itself could result in dyslipidemia (Shen et al, 2015). The prevalence of hypercholesteremia and hypertriglyceridemia in ART-naïve HIV-infected patients were similar to previous reports from China (Shen et al, 2015) and Africa (Armstrong et al, 2011).…”

Multiple drug-resistant HBV mutation may contribute to poor response of adefovir + entecavir in entecavir-resistant patients

“…TDF and TDF+ETV have been previously reported to be efficient for the treatment of ETV-resistant patients [33−36], including Chinese patients [31,37,38]. Our results reinforced the fact that TDF-based rescue therapy was efficient in ETV-resistant patients who had an inadequate VR upon ADV+ETV rescue therapy.…”

Guidelines for Prevention and Treatment of Chronic Hepatitis B

“…In addition, virological response rates increased during treatment. [129][130][131][132][133][134][135][136][137][138][139] Tenofovir alafenamide fumarate tablets (TAF): In a global phase III clinical trial, 581 HBeAg-positive CHB patients (which excluded patients with decompensated cirrhosis) received TAF treatment for 48 weeks. HBV DNA levels were <29 IU/mL in 64% of patients and ALT levels returned to normal in 72% of patients.…”