The anti-HIV activity of entecavir: a multicentre evaluation of lamivudine-experienced and lamivudine-naive patients

Abstract

Background: Entecavir, an antiviral with potent anti-hepatitis B virus activity, was recently shown to have anti-HIV activity in three patients and the ability to select for the lamivudine-resistant HIV polymerase mutation M184V in a patient with prior antiretroviral therapy.

Objectives: To further characterize entecavir's anti-HIV activity and identify risk factors for selection of the M184V.

Design: Retrospective cohort study.

Methods: We evaluated the virological characteristics of HIV and hepatitis B virus in 17 HIV-hepatitis B virus coinfected patients (10 antiretroviral therapy-naive and seven antiretroviral therapy-experienced) prior to and during entecavir monotherapy. Descriptive statistics were used to assess changes in HIV RNA and hepatitis B virus DNA. Variables associated with development of the M184V were determined by univariate analysis.

Results: Of the 17 patients, 13 (76%) demonstrated a reduction in HIV RNA by at least 0.5 log10 copies/ml. Of the remaining four patients, two had the M184V detected prior to entecavir therapy and the other two had wild-type HIV. The median reduction in HIV RNA for the cohort was 1.2 log10 copies/ml, which was similar in antiretroviral therapy-naive and antiretroviral therapy-experienced patients. The M184V mutation emerged in six patients receiving entecavir, including three antiretroviral therapy-naive patients. No other HIV mutations were consistently detected. Risk factors for the emergence of the M184V mutation were a decline in hepatitis B virus DNA (P = 0.04) and duration of entecavir use (P = 0.05).

Conclusion: Entecavir monotherapy in HIV-hepatitis B virus coinfected patients, including antiretroviral therapy-naive patients, has significant anti-HIV activity and can result in the development of the M184V variant. Entecavir should not be used in such co-infected patients without concomitant antiretroviral therapy.

Figure 1. Changes in HIV RNA and HBV DNA in ART-naive (Patients 1-10) and ART-experienced (patients 11-17) HIV-HBV co-infected patients

Changes in HIV RNA (black) and HBV DNA (blue) are shown prior to and following entecavir. The time of collection of plasma for sequencing of HIV RT is shown as a black arrow.