Low Incidence of Resistance to Entecavir after 48 Weeks of Treatment in HIV-HBV Coinfected Patients 

By Marina Nunez, MD, PhD

Entecavir (Baraclude) is a selective HBV inhibitor that has not shown emergence of resistance mutations in naïve patients after two years of therapy.  Lamivudine (3TC; Epivir-HBV) resistance mutations result in an 8-fold decrease in susceptibility to entecavir, and are a prerequisite for virological rebound due to entecavir resistance. Surveillance of HBV resistance mutations was performed in patients included in a study evaluating the efficacy of entecavir in the treatment of 3TC-experienced HIV-HBV-coinfected patients.

The study (AI463038) had two phases, a double-blind phase for the first 24 weeks, and an open-label phase from weeks 24 to 48 of therapy. All patients were 3TC-experienced and continued receiving the drug throughout the study. From baseline, 51 patients received entecavir and 17 placebo, in addition to 3TC. From week 24 all patients (N=65) received entecavir plus 3TC.

The median decrease in HBV DNA levels was of -4.2 log by week 48, with 84% patients experiencing at least a 2-log₁₀ decrease by week 24, and 9% with HBV DNA levels under the limit of detection (300 copies/mL) at week 48. No virological rebounds were observed throughout the study period.

At study entry, 48 of the 50 (96%) samples sequenced had 3TC resistance substitutions (rtM204I/V ± rtL180M) in the HBV reverse transcriptase, while none had ETV resistance substitutions (rtT184, rtS202, rtM250) detectable by standard sequencing. Detection of mutations rtT184S and rtS202C was evident in two patients at week 48, and both substitutions were subsequently found at study entry using a highly sensitive single nucleotide polymorphism assay.

On entecavir treatment, 19 novel substitutions also emerged, but none were correlated with reduced susceptibility to entecavir in phenotypic assays.

In summary, entecavir given to HIV-HBV-coinfected patients with 3TC refractory HBV caused an increase in the presence of entecavir resistant HBV variants already present at study entry in a small proportion of patients. However it was not translated into virological rebounds within 48 weeks of therapy. The authors conclude, “Entecavir is a valuable treatment option for chronic HBV in patients coinfected with HIV.”

02/21/06

Reference
R Colonno and others. Week 48 resistance surveillance of HIV/HBV coinfected patients treated with entecavir in study AI463038. 13^th Conference on Retroviruses and Opportunistic Infections. February 5-8, 2006, Denver, CO. Abstract 832.