Maintenance of Complete Viral Suppression (CVS) with Tenofovir (TDF) Monotherapy Following CVS with Entecavir (ETV)+TDF Combination in Patients with Prior ETV Partial Response

Abstract

Purpose: Recent studies indicated that ETV partial responders (PR) can attain CVS with ETV+TDF combination therapy. However, it is not clear if ETV PR can continue to maintain CVS after achieving CVS with combination therapy. Our goal was to examine virologic outcomes of ETV PR treated with ETV or TDF monotherapy following CVS with combination therapy. Methods: We retrospectively studied 57 consecutive patients with ETV PR who subsequently achieved CVS (undetectable HBV DNA PCR) with ETV+TDF combination therapy at 3 U.S. liver clinics. Patients with confirmed antiviral resistance were excluded. HBV polymerase mutation analysis was performed in all patients prior to initiation of combination therapy. Virologic breakthrough was defined as an increase of HBV DNA by ≥1 log IU/mL from nadir. Results: The majority of patients were Asian (96%), male (65%) and HBeAg-positive (95%) with a median age of 38 (22-67) years. A few patients (28%) had previous exposure to lamivudine (16%) or adefovir (19%) prior to initial ETV monotherapy. All patients achieved CVS with ETV+TDF combination after a median of 5 (2-26) months. Following CVS with combination therapy, 13 patients were switched to ETV monotherapy and 20 patients were switched to TDF monotherapy, while 24 patients remained on combination therapy. Cumulative incidence of virologic breakthrough was significantly higher in patients who returned to ETV monotherapy at 6 months (69% vs. 41%, p<0.0001) and 12 months (92% vs. 54%, p<0.0001) compared to patients who switched to TDF monotherapy (Figure 1). Five patients (21%) experienced virologic breakthrough while continuing on combination therapy. Four patients achieved CVS again, suggesting possible medication nonadherence. The other patient admitted to being nonadherent at time of virologic breakthrough.Figure 1: Incidence of cumulative virologic breakthrough with monotherapy following complete viral suppression with ETV and TDF combination therapy.Conclusion: For patients with prior PR to ETV but achieved CVS with combination therapy, TDF monotherapy may be a reasonable option in half of the patients. The economic savings and convenience advantage can be considerable for those who can maintain CVS solely on TDF monotherapy instead of combination therapy. Nonadherence also appears to be a significant issue with combination therapy. Disclosure: Kevin T. Chaung - No financial relationship with a commercial interest; Nghiem B. Ha - No financial relationship with a commercial interest; Kevin C. Kin - No financial relationship with a commercial interest; Huy Trinh - Consultant: Bristol-Myers Squibb, Grant/Research Support: Gilead Sciences Inc., Roche, Stockholder/Ownership Interest: Gilead Sciences Inc., Bristol-Myers Squibb, Advisory Committee/Board Member: Bristol-Myers Squibb, Gilead Sciences Inc.; Huy Nguyen - Speaker's Bureau: Gilead Sciences Inc.; Mindie Nguyen - Consultant: Bristol-Myers Squibb, Gilead Sciences Inc., Bayer, Grant/Research Support: Bristol-Myers Squibb, Novartis Pharmaceuticals, Gilead Sciences Inc.; Roche, Gilead Sciences Inc.