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Volume 356:2614-2621 June 21, 2007 Number 25
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The HBV Drug Entecavir — Effects on HIV-1 Replication and Resistance
Moira A. McMahon, B.S., Benjamin L. Jilek, B.S., Timothy P. Brennan, M.S., Lin Shen, M.D., Yan Zhou, Ph.D., Megan Wind-Rotolo, Ph.D., Sifei Xing, B.S., Shridhar Bhat, Ph.D., Braden Hale, M.D., Robert Hegarty, M.S.N., Curtis R. Chong, M.Phil., Jun O. Liu, Ph.D., Robert F. Siliciano, M.D., Ph.D., and Chloe L. Thio, M.D.

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 by Hirsch, M. S.

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SUMMARY

Entecavir, a drug approved by the Food and Drug Administration for the treatment of chronic hepatitis B virus (HBV) infection, is not believed to inhibit replication of human immunodeficiency virus type 1 (HIV-1) at clinically relevant doses. We observed that entecavir led to a consistent 1-log10 decrease in HIV-1 RNA in three persons with HIV-1 and HBV coinfection, and we obtained supportive in vitro evidence that entecavir is a potent partial inhibitor of HIV-1 replication. Detailed analysis showed that in one of these patients, entecavir monotherapy led to an accumulation of HIV-1 variants with the lamivudine-resistant mutation, M184V. In vitro experiments showed that M184V confers resistance to entecavir. Until more is known about HIV-1–resistance patterns and their selection by entecavir, caution is needed with the use of entecavir in persons with HIV-1 and HBV coinfection who are not receiving fully suppressive antiretroviral regimens.


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From the Departments of Pharmacology and Molecular Sciences (M.A.M., L.S., S.X., S.B., C.R.C., J.O.L.) and Medicine (B.L.J., T.P.B., Y.Z., M.W.-R., R.H., R.F.S., C.L.T.), Johns Hopkins University School of Medicine; and the Howard Hughes Medical Institute (R.F.S.) — both in Baltimore; and the Division of Infectious Diseases, Naval Medical Center, San Diego, San Diego, CA (B.H.).

Address reprint requests to Dr. Thio at the Department of Medicine, Johns Hopkins University School of Medicine, 1503 E. Jefferson St., Baltimore, MD 21231, or at cthio{at}jhmi.edu.

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