Entecavir is effective against 3TC-resistant hepatitis B

An international, phase II study of the anti-hepatitis B drug Entecavir (ETV) showed that in HIV-HBV coinfected patients with 3TC-resistant HBV, adding ETV therapy reduced HBV DNA and normalised ALT within 24 weeks, with tolerability comparable to placebo. No interaction with HIV infection or HAART was reported.

ETV-038 is an ongoing, double blind, comparative trial with 68 coinfected participants who had HBV viraemia while being treated with 3TC. The study included sites in Brazil, UK, USA, Argentina and Spain. Most (88%) had HBV with at least one 3TC-resistant mutation. Patients were randomised to receive ETV 1mg (n=51) or placebo (n=17) once-daily for 24 weeks followed by open label ETV for all participants for another 24 weeks. All patients continued taking 3TC.

The mean baseline HBV viral load was 9.13 log10 copies/mL. The mean reduction in HBV DNA at 24 weeks was greater in the ETV group than in the placebo group (-3.66 vs +0.11log10 copies/mL, p<0.0001), with 84% vs 0% achieving either <400 copies/mL or a >/= 2 log10 reduction from baseline (p<0.0001). After 24 weeks, ALT had normalised in 49% in the ETV group compared to 0% in the placebo group (p=0.05).

Frequency of adverse events was comparable between the two groups after a mean follow-up of more than 40 weeks. There were no significant changes in HIV viraemia or in CD4 count in either group.

Comment

On March 11, the FDA Antiviral Drug Advisory Committee voted to approve entecavir for first- and second-line therapy based on studies in HBV monoinfected patients. They also recommended comparative studies be conducted between entecavir and adefovir and tenofovir.

ETV was equivalent (non-inferior) to lamivudine for the secondary histologic endpoint of improvement in Ishak fibrosis score in the nucleoside-naïve studies but was superior in the lamivudine-refractory patient population.

There was discussion at the FDA public hearing about paediatric use. BMS applied for approval of pills & oral solution. There is no paediatric PK and safety data, and this is the population that would use the oral solution.

Pessoa W, Gazzard B, Huang A et al. Entecavir in HIV/HBV-co-infected patients: safety and efficacy in a phase II study (ETV-038). 12th CROI, Boston, 2005.
Abstract 123.