Entecavir for HBV May Result in HIV Drug Resistance

Emma Hitt, PhD

August 16, 2007 — Use of entecavir (Baraclude) by patients coinfected with HIV and hepatitis B virus who are not already receiving highly active antiretroviral therapy (HAART) may result in resistance to nucleoside reverse transcriptase inhibitors (NRTIs), according to an alert sent today from MedWatch, the US Food and Drug Administration (FDA) adverse event and reporting program. The full prescribing information for entecavir, including the boxed warning, has been updated to include this information.
Entecavir, manufactured by Bristol-Myers Squibb (BMS), is indicated for the treatment of chronic hepatitis B virus in adults who show evidence of active viral replication and who have either histologically active disease or persistent elevations in serum aminotransferases (ALT or AST).
The microbiology section of the entecavir prescribing information was also updated to include a statement about the inhibitory activity of entecavir against HIV-1 isolates. Entecavir selected for an M184I substitution in HIV reverse transcriptase at micromolar concentrations in cell culture, indicating inhibitory pressure at high entecavir concentrations, and HIV variants containing the M184V substitution showed loss of susceptibility to entecavir.
In addition, the warnings section has been updated to state that before starting therapy with entecavir, all patients should be offered HIV antibody testing and that entecavir has not been evaluated for treatment of HIV infection.