The HBV drug entecavir - effects on HIV-1 replication and resistance.
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.
McMahon
Moira A
MA
Department of Pharmacology and Molecular Sciences, Johns Hopkins University School of Medicine, Baltimore, MD 21231, USA.
Jilek
Benjamin L
BL
Brennan
Timothy P
TP
Shen
Lin
L
Zhou
Yan
Y
Wind-Rotolo
Megan
M
Xing
Sifei
S
Bhat
Shridhar
S
Hale
Braden
B
Hegarty
Robert
R
Chong
Curtis R
CR
Liu
Jun O
JO
Siliciano
Robert F
RF
Thio
Chloe L
CL
D000328:Adult; D000998:Antiviral Agents / Q000494:pharmacology* / Q000627:therapeutic use; D018791:CD4 Lymphocyte Count; D024882:Drug Resistance, Viral; D006147:Guanine / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D015658:HIV Infections / Q000150:complications / Q000188:drug therapy* / Q000821:virology; D054303:HIV Reverse Transcriptase / Q000235:genetics; D015497:HIV-1 / Q000187:drug effects* / Q000235:genetics / Q000502:physiology; D006509:Hepatitis B / Q000150:complications / Q000188:drug therapy*; D006515:Hepatitis B virus; D006801:Humans; D019259:Lamivudine / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D009154:Mutation; D010802:Phylogeny; D012367:RNA, Viral / Q000097:blood; D018894:Reverse Transcriptase Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D048348:Reverse Transcription / Q000187:drug effects; D014779:Virus Replication / Q000187:drug effects*; D015215:Zidovudine / Q000627:therapeutic use
D000998:Antiviral Agents; D012367:RNA, Viral; D018894:Reverse Transcriptase Inhibitors; D019259:Lamivudine; D015215:Zidovudine; C413685:entecavir; D006147:Guanine; D054303:HIV Reverse Transcriptase