Multicenter Evaluation Sheds Further Light on Anti-HIV Activity of Entecavir (Baraclude)

By Liz Highleyman

At the 2007 Conference on Retroviruses and Opportunistic Infections (CROI), researchers reported that entecavir (Baraclude), a nucleoside analog approved for the treatment of chronic hepatitis B virus (HBV) infection, also has unexpected antiviral activity against HIV.

Baraclude Tablet

In vitro experiments demonstrated that entecavir monotherapy could select for the M184V drug resistance mutation, which also confers resistance to the antiretroviral agents lamivudine (3TC; Epivir) and emtricitabine (Emtriva), which are common components of HAART regimens.

Entecavir had previously been recommended for HIV-HBV coinfected individuals who did not yet require combination antiretroviral therapy, but when its anti-HIV activity was recognized, the U.S. Food and Drug Administration (FDA) warned against using entecavir monotherapy in such patients, and the current U.S. HIV treatment guidelines recommend that all HIV-HBV patients who need treatment for hepatitis B should receive combination HAART.

Since the CROI presentation, several other research teams have reported on the anti-HIV activity of entecavir, including a multicenter evaluation by Australian investigators described in the May 11, 2008, issue of AIDS.

In an effort to further characterize the anti-HIV activity of entecavir and to identify risk factors for selection of the M184V mutation, the authors conducted a retrospective cohort study to evaluate the virological characteristics of HIV and HBV in 17 coinfected patients prior to and during entecavir monotherapy. Of these study participants, 10 were antiretroviral-naive and 7 had previously used antiretroviral drugs.

Results

• Of the 17 patients, 13 (76%) demonstrated a reduction in HIV RNA of at least 0.5 log10 copies/mL while taking entecavir.

• The median reduction in HIV RNA for the cohort was 1.2 log10 copies/mL, which was similar in the antiretroviral-naive and antiretroviral-experienced patients.

• Of the remaining 4 participants, 2 had the M184V mutation detected prior to entecavir therapy, and the other 2 had wild-type HIV.

• The M184V mutation emerged anew in 6 patients receiving entecavir, including 3 antiretroviral-naive patients.

• Risk factors for the emergence of the M184V mutation were a decline in HBV DNA (P = 0.04) and longer duration of entecavir use (P = 0.05).

• No other HIV mutations were consistently detected.

Based on these findings, the study authors concluded that, "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," they recommended.

6/20/08

Reference
J Sasadeusz, J Audsley, A Mijch, and others. The anti-HIV activity of entecavir: a multicentre evaluation of lamivudine-experienced and lamivudine-naive patients. AIDS 22(8): 947-955. May 11, 2008.