The HBV drug entecavir - Effects on HIV-1 replication and resistance

Moira A. McMahon; Benjamin L. Jilek; Timothy P. Brennan; Lin Shen; Yan Zhou; Megan Wind-Rotolo; Sifei Xing; Shridhar Bhat; Braden Hale; Robert Hegarty; Curtis R. Chong; Jun O. Liu; Robert F. Siliciano; Chloe L. Thio

doi:10.1056/NEJMoa067710

The HBV drug entecavir - Effects on HIV-1 replication and resistance

Moira A. McMahon, Benjamin L. Jilek, Timothy P. Brennan, Lin Shen, Yan Zhou, Megan Wind-Rotolo, Sifei Xing, Shridhar Bhat, Braden Hale, Robert Hegarty, Curtis R. Chong, Jun O. Liu, Robert F. Siliciano, Chloe L. Thio

Research output: Contribution to journal › Article › peer-review

223 Scopus citations

Abstract

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-log ₁₀ 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.

Original language	English (US)
Pages (from-to)	2614-2621
Number of pages	8
Journal	New England Journal of Medicine
Volume	356
Issue number	25
DOIs	https://doi.org/10.1056/NEJMoa067710
State	Published - Jun 21 2007

ASJC Scopus subject areas

General Medicine

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title = "The HBV drug entecavir - Effects on HIV-1 replication and resistance",

abstract = "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-log 10 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.",

author = "McMahon, {Moira A.} and Jilek, {Benjamin L.} and Brennan, {Timothy P.} and Lin Shen and Yan Zhou and Megan Wind-Rotolo and Sifei Xing and Shridhar Bhat and Braden Hale and Robert Hegarty and Chong, {Curtis R.} and Liu, {Jun O.} and Siliciano, {Robert F.} and Thio, {Chloe L.}",

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doi = "10.1056/NEJMoa067710",

language = "English (US)",

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AU - McMahon, Moira A.

AU - Jilek, Benjamin L.

AU - Brennan, Timothy P.

AU - Shen, Lin

AU - Zhou, Yan

AU - Wind-Rotolo, Megan

AU - Xing, Sifei

AU - Bhat, Shridhar

AU - Hale, Braden

AU - Hegarty, Robert

AU - Chong, Curtis R.

AU - Liu, Jun O.

AU - Siliciano, Robert F.

AU - Thio, Chloe L.

PY - 2007/6/21

Y1 - 2007/6/21

N2 - 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-log 10 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.

AB - 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-log 10 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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The HBV drug entecavir - Effects on HIV-1 replication and resistance

Abstract

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