Reuters Health Information (2007-03-02): HBV antiviral induces HIV-1-resistance
HBV antiviral induces HIV-1-resistance
Last Updated: 2007-03-02 17:27:53 -0400 (Reuters Health)
LOS ANGELES (Reuters Health) - Entecavir, approved in the U.S by the FDA for the treatment of chronic hepatitis B, is active against HIV-1, and if given as monotherapy to co-infected patients, can produce a common resistance mutation that may limit patients' future antiretroviral options.
Dr. Chloe Thio, an investigator from Johns Hopkins University in Baltimore, presented these findings on behalf of her colleagues at the 14th Annual Retroviral Conference here this week.
Although entecavir's package insert states it has no clinically relevant activity against HIV-1, Dr. Thio and her associates noticed that in a group of HBV-infected patients they were following, two co-infected patients exhibited a sudden 1-log decline in HIV-1 RNA.
Since these patients had not yet begun antiretroviral therapy, the investigators hypothesized that entecavir may have been responsible for the sudden reduction in viral load.
Dose-response curves were generated to measure HIV-1 inhibition. Next, the researchers used an HIV-1 pseudovirus with pol gene sequences from a reference strain or from an infected patient to infect CD4 cells in vitro.
The investigators added increasing doses of entecavir and measured HIV-1 levels at different time points and also looked at viral mutations. As they suspected, entecavir was a potent inhibitor of HIV in laboratory strains and those taken from patients. .Monotherapy gave rise to several HIV-1 mutations, including M184V. In one patient four different mutations were detected.
M184V confers resistance to antiretrovirals such a lamivudine and other drugs that "serve as the cornerstone of highly active antiretroviral therapy," she said. This seriously limits future treatment options.
Although the manufacturer advises that entecavir is safe for HIV-1-infected patients who have not begun antiretroviral therapy, the development of resistance makes treatment questionable for these patients.