No detectable resistance to tenofovir disoproxil fumarate after 6 years of therapy in patients with chronic hepatitis B.
One major challenge in the treatment of chronic hepatitis B is to maintain long-term viral suppression without promoting the selection of drug-resistant mutations. We analyzed data from 347 hepatitis B e antigen-negative and 238 hepatitis B e antigen positive patients receiving tenofovir disoproxil fumarate (TDF) in an open-label, longterm extension of two phase 3 studies. To date, resistance analyses have been completed for patients receiving up to 288 weeks (6 years) of TDF. Population sequencing of hepatitis B virus (HBV) polymerase/reverse transcriptase (pol/RT) was attempted for all patients at baseline, and any patient who remained viremic (HBV DNA 400 copies/mL [69 IU/mL]) at week 288 or at the end of treatment with TDF (n552) or emtricitabine(FTC)/TDF (n57). Phenotypic analyses were performed in HepG2 cells using recombinant HBV containing patient pol/RT sequences. Approximately half of the patients on open-label treatment who qualified for genotyping had pol/RT sequence changes compared to baseline (23/52 [44%] on TDF, 4/7 [57%] on FTC/TDF). Most changes were at polymorphic sites and none were associated with TDF resistance. Virologic breakthrough occurred infrequently and was associated with nonadherence to study medication in the majority of cases (12/16, 75%). Per protocol, 57 patients (10%)were eligible to switch to FTC/TDF; the majority had HBV DNA <400 copies/mL at their last study visit regardless of whether they switched to FTC/TDF (n534) or maintained TDF monotherapy (n517). No patient exhibited persistent viremia (HBV DNA never <400 copies/mL) after week 240.


CONCLUSIONS
TDF monotherapy maintains effective suppression of HBV DNA through 288 weeks of treatment with no evidence of TDF resistance.
Kathryn M
KM
Kitrinos
Amoreena
A
Corsa
Yang
Y
Liu
John
J
Flaherty
Andrea
A
Snow-Lampart
Patrick
P
Marcellin
Katyna
K
Borroto-Esoda
Michael D
MD
Miller
D000225:Adenine / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D000998:Antiviral Agents / Q000494:pharmacology* / Q000627:therapeutic use*; D004279:DNA, Viral / Q000235:genetics; D004311:Double-Blind Method; D024882:Drug Resistance, Viral / Q000187:drug effects*; D005838:Genotype; D006515:Hepatitis B virus / Q000187:drug effects*; D019694:Hepatitis B, Chronic / Q000188:drug therapy*; D006801:Humans; D008137:Longitudinal Studies; D009154:Mutation / Q000235:genetics; D010349:Patient Compliance; D010641:Phenotype; D010757:Phosphorous Acids / Q000494:pharmacology* / Q000627:therapeutic use*; D015995:Prevalence; D016896:Treatment Outcome; D014766:Viremia / Q000453:epidemiology
C574165:9-(2-((bis(pivaloyloxymethoxy)phosphinoyl)methoxy)propyl)adenine; D000998:Antiviral Agents; D004279:DNA, Viral; D010757:Phosphorous Acids; D000225:Adenine