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.

[1]  E. De Clercq,et al.  Inhibitory effect of 9-(2-phosphonylmethoxyethyl)-adenine (PMEA) on human and duck hepatitis B virus infection. , 1993, Antiviral research.

[2]  Acip.  Prevention and control of influenza : recommendations of the Advisory Committee on Immunization Practices (ACIP) , 2004 .

[3]  B. Tehan,et al.  Comparisons of the Hbv and HIV Polymerase, and Antiviral Resistance Mutations , 2003, Antiviral therapy.

[4]  R. Siliciano,et al.  Novel Single-Cell-Level Phenotypic Assay for Residual Drug Susceptibility and Reduced Replication Capacity of Drug-Resistant Human Immunodeficiency Virus Type 1 , 2004, Journal of Virology.

[5]  Ying,et al.  Lamivudine, adefovir and tenofovir exhibit long‐lasting anti‐hepatitis B virus activity in cell culture , 2000, Journal of viral hepatitis.

[6]  L. Mofenson,et al.  Treating opportunistic infections among HIV-exposed and infected children: recommendations from CDC, the National Institutes of Health, and the Infectious Diseases Society of America. , 2005, Clinical infectious diseases : an official publication of the Infectious Diseases Society of America.

[7]  J. J. Henning,et al.  Guidelines for the Use of Antiretroviral Agents in HIV-Infected Adults and Adolescents, January 28, 2000 , 1998, HIV clinical trials.

[8]  S D Kemp,et al.  Rapid in vitro selection of human immunodeficiency virus type 1 resistant to 3'-thiacytidine inhibitors due to a mutation in the YMDD region of reverse transcriptase. , 1993, Proceedings of the National Academy of Sciences of the United States of America.

[9]  Christos J. Petropoulos,et al.  A Novel Phenotypic Drug Susceptibility Assay for Human Immunodeficiency Virus Type 1 , 2000, Antimicrobial Agents and Chemotherapy.

[10]  R. Schinazi,et al.  Inhibition of the replication of hepatitis B virus in vitro by 2',3'-dideoxy-3'-thiacytidine and related analogues. , 1991, Proceedings of the National Academy of Sciences of the United States of America.

[11]  R. Rathbun,et al.  Current HIV treatment guidelines--an overview. , 2006, Current pharmaceutical design.

[12]  R. Colonno,et al.  Identification of BMS-200475 as a potent and selective inhibitor of hepatitis B virus , 1997, Antimicrobial agents and chemotherapy.

[13]  Joel E Gallant,et al.  Nucleoside and Nucleotide Analogue Reverse Transcriptase Inhibitors: A Clinical Review of Antiretroviral Resistance , 2002, Antiviral therapy.

[14]  Claus O. Wilke,et al.  Residual Human Immunodeficiency Virus Type 1 Viremia in Some Patients on Antiretroviral Therapy Is Dominated by a Small Number of Invariant Clones Rarely Found in Circulating CD4+ T Cells , 2006, Journal of Virology.

[15]  B. Rodés,et al.  Risk of selecting K65R in antiretroviral-naive HIV-infected individuals with chronic hepatitis B treated with adefovir , 2005, AIDS.

[16]  C. Tural,et al.  Consensus conference on chronic viral hepatitis and HIV infection: updated Spanish recommendations , 2004, Journal of viral hepatitis.

[17]  Keri A. Sims,et al.  Entecavir: A New Nucleoside Analog for the Treatment of Chronic Hepatitis B Infection , 2006, Pharmacotherapy.

[18]  R. J. Colonno,et al.  Efficacies of Entecavir against Lamivudine-Resistant Hepatitis B Virus Replication and Recombinant Polymerases In Vitro , 2002, Antimicrobial Agents and Chemotherapy.

[19]  Jerome A. Zack,et al.  HIV-1 entry into quiescent primary lymphocytes: Molecular analysis reveals a labile, latent viral structure , 1990, Cell.

[20]  W. Keulen,et al.  Reduced replication of 3TC‐resistant HIV‐1 variants in primary cells due to a processivity defect of the reverse transcriptase enzyme. , 1996, The EMBO journal.

[21]  J. Sninsky,et al.  Rapid changes in human immunodeficiency virus type 1 RNA load and appearance of drug-resistant virus populations in persons treated with lamivudine (3TC). , 1995, The Journal of infectious diseases.

[22]  R F Schinazi,et al.  Characterization of human immunodeficiency viruses resistant to oxathiolane-cytosine nucleosides , 1993, Antimicrobial Agents and Chemotherapy.

[23]  M. Wainberg,et al.  The same mutation that encodes low-level human immunodeficiency virus type 1 resistance to 2',3'-dideoxyinosine and 2',3'-dideoxycytidine confers high-level resistance to the (-) enantiomer of 2',3'-dideoxy-3'-thiacytidine , 1993, Antimicrobial Agents and Chemotherapy.

[24]  S. Sarafianos,et al.  The M184V Mutation Reduces the Selective Excision of Zidovudine 5′-Monophosphate (AZTMP) by the Reverse Transcriptase of Human Immunodeficiency Virus Type 1 , 2002, Journal of Virology.

[25]  M. Winters,et al.  Potent Efficacy of Entecavir (BMS-200475) in a Duck Model of Hepatitis B Virus Replication , 2002, Antimicrobial Agents and Chemotherapy.

[26]  M. Boyd,et al.  New soluble-formazan assay for HIV-1 cytopathic effects: application to high-flux screening of synthetic and natural products for AIDS-antiviral activity. , 1989, Journal of the National Cancer Institute.

[27]  P. Karayiannis.  Hepatitis B virus: old, new and future approaches to antiviral treatment. , 2003, The Journal of antimicrobial chemotherapy.

[28]  P. Egli,et al.  Metabolic Studies on BMS-200475, a New Antiviral Compound Active against Hepatitis B Virus , 1999, Antimicrobial Agents and Chemotherapy.

[29]  Thomas C. Quinn,et al.  Persistence of Wild-Type Virus and Lack of Temporal Structure in the Latent Reservoir for Human Immunodeficiency Virus Type 1 in Pediatric Patients with Extensive Antiretroviral Exposure , 2002, Journal of Virology.