This Article Full Text (PDF) Other Versions of this Article: AAC.01313-07v1 52/5/1759    most recent Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Reprints and Permissions Copyright Information Books from ASM Press MicrobeWorld Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Lin, P.-F. Articles by Colonno, R. Search for Related Content PubMed PubMed Citation Articles by Lin, P.-F. Articles by Colonno, R.

 Previous Article  |  Next Article 

Antimicrob. Agents Chemother. doi:10.1128/AAC.01313-07
Copyright (c) 2008, American Society for Microbiology and/or the Listed Authors/Institutions. All Rights Reserved.

Entecavir Exhibits Inhibitory Activity Against HIV Under Conditions of Reduced Viral Challenge

Bristol-Myers Squibb Pharmaceutical Research and Development, Wallingford, CT, USA; Monogram Biosciences, South San Francisco, CA, USA

^* To whom correspondence should be addressed. Email: Pinfang.Lin{at}bms.com.

	Abstract

Entecavir (ETV) was developed for the treatment of chronic hepatitis B virus (HBV) infection and is globally approved for that indication. Initial preclinical studies indicated that ETV had no significant activity against human immunodeficiency virus- type 1 (HIV-1) in cultured cell lines at physiologically relevant ETV concentrations using traditional anti-HIV assays. In response to recent clinical observations of anti-HIV activity of ETV in HIV/HBV co-infected patients not receiving HAART, additional investigative studies were conducted to expand upon earlier results. An extended panel of HIV-1 laboratory and clinical strains and cell types were tested against ETV, along with a comparison of assay methodologies and resistance profiling. These latest studies confirmed that ETV has only weak activity against HIV in established assay systems. However, a >100-fold enhancement of antiviral activity (equivalent to the antiviral activity of lamivudine) could be obtained when assay conditions were modified to reduce the initial viral challenge. Also, selection of a M184I viral variant during passage of HIV-1 at high concentrations of ETV confirmed that ETV can exert inhibitory pressure on the virus. These findings may have a significant impact on how future assays are performed on compounds to be used in those infected with HIV. These results support the recommendation that ETV therapy in HIV/HBV co-infected patients should be administered in concert with HAART.

This article has been cited by other articles:

• (2008). Entecavir Inhibits HIV at Reduced Viral Inoculum. JWatch Infect. Diseases 2008: 2-2 [Full Text]