This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowReprints and Permissions
Right arrow Copyright Information
Right arrow Books from ASM Press
Right arrow MicrobeWorld
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Harrigan, P. R.
Right arrow Articles by Larder, B. A.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Harrigan, P. R.
Right arrow Articles by Larder, B. A.

 Previous Article  |  Next Article 

Antimicrobial Agents and Chemotherapy, April 2002, p. 1067-1072, Vol. 46, No. 4
0066-4804/02/$04.00+0     DOI: 10.1128/AAC.46.4.1067-1072.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.

Phenotypic Susceptibilities to Tenofovir in a Large Panel of Clinically Derived Human Immunodeficiency Virus Type 1 Isolates

P. R. Harrigan,1 M. D. Miller,2 P. McKenna,3 Z. L. Brumme,1 and B. A. Larder4*

BC Centre for Excellence in HIV/AIDS, St. Paul's Hospital, Vancouver, British Columbia, Canada,1 Gilead Sciences, Foster City, California,2 Virco NV, Mechelen, Belgium,3 Virco, Cambridge, United Kingdom4

Received 9 August 2001/ Returned for modification 6 November 2001/ Accepted 15 January 2002

Tenofovir is a nucleotide analogue human immunodeficiency virus type 1 (HIV-1) reverse transcriptase (RT) inhibitor, and its oral prodrug, tenofovir disoproxil fumarate, has recently been approved for the treatment of HIV-1 infection in the United States. The objective of this study was to characterize the in vitro susceptibility profiles of a large panel of clinically derived HIV-1 isolates for tenofovir. The distribution of tenofovir susceptibilities in over 1,000 antiretroviral-naive, HIV-1-infected individuals worldwide was determined using the Virco Antivirogram assay. In addition, phenotypic susceptibilities to tenofovir and other RT inhibitors were determined in a panel of nearly 5,000 recombinant HIV-1 clinical isolates from predominantly treatment-experienced patients analyzed as a part of routine drug resistance testing. Greater than 97.5% of isolates from treatment-naive patients had tenofovir susceptibilities <3-fold above those of the wild-type controls by the Antivirogram. The clinically derived panel of 5,000 samples exhibited a broad range of antiretroviral drug susceptibilities, including 69, 43, and 16% having >10-fold-decreased susceptibilities to at least one, two, and three antiretroviral drug classes, respectively. Greater than 88% of these 5,000 clinical isolates were within the threefold susceptibility range for tenofovir, and >99% exhibited <10-fold-reduced susceptibilities to tenofovir. Decreased susceptibility to tenofovir was not directly associated with resistance to other RT inhibitors; r2 values of log-log linear regression plots of susceptibility to tenofovir versus susceptibility to other RT inhibitors were <0.4. The results suggest that the majority of treatment-naive and treatment-experienced individuals harbor HIV that remains within the normal range of tenofovir susceptibilities and may be susceptible to tenofovir disoproxil fumarate therapy.

* Corresponding author. Present address: Visible Genetics, 184 Cambridge Science Park, Cambridge CB4 0GA, United Kingdom. Phone: (44) 1223 728 800. Fax: (44)1223 728 801. E-mail: blarder{at}visgen.com.

Antimicrobial Agents and Chemotherapy, April 2002, p. 1067-1072, Vol. 46, No. 4
0066-4804/02/$04.00+0     DOI: 10.1128/AAC.46.4.1067-1072.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Blum, M. R., Chittick, G. E., Begley, J. A., Zong, J. (2007). Steady-State Pharmacokinetics of Emtricitabine and Tenofovir Disoproxil Fumarate Administered Alone and in Combination in Healthy Volunteers. J Clin Pharmacol 47: 751-759 [Abstract] [Full Text]  
  • Winters, M. A., Merigan, T. C. (2005). Insertions in the Human Immunodeficiency Virus Type 1 Protease and Reverse Transcriptase Genes: Clinical Impact and Molecular Mechanisms. Antimicrob. Agents Chemother. 49: 2575-2582 [Full Text]  
  • Boyer, P. L., Imamichi, T., Sarafianos, S. G., Arnold, E., Hughes, S. H. (2004). Effects of the {Delta}67 Complex of Mutations in Human Immunodeficiency Virus Type 1 Reverse Transcriptase on Nucleoside Analog Excision. J. Virol. 78: 9987-9997 [Abstract] [Full Text]  
  • Matamoros, T., Franco, S., Vazquez-Alvarez, B. M., Mas, A., Martinez, M. A., Menendez-Arias, L. (2004). Molecular Determinants of Multi-nucleoside Analogue Resistance in HIV-1 Reverse Transcriptases Containing a Dipeptide Insertion in the Fingers Subdomain: EFFECT OF MUTATIONS D67N AND T215Y ON REMOVAL OF THYMIDINE NUCLEOTIDE ANALOGUES FROM BLOCKED DNA PRIMERS. J. Biol. Chem. 279: 24569-24577 [Abstract] [Full Text]  
  • Van Rompay, K. K. A., Brignolo, L. L., Meyer, D. J., Jerome, C., Tarara, R., Spinner, A., Hamilton, M., Hirst, L. L., Bennett, D. R., Canfield, D. R., Dearman, T. G., Von Morgenland, W., Allen, P. C., Valverde, C., Castillo, A. B., Martin, R. B., Samii, V. F., Bendele, R., Desjardins, J., Marthas, M. L., Pedersen, N. C., Bischofberger, N. (2004). Biological Effects of Short-Term or Prolonged Administration of 9-[2-(Phosphonomethoxy)Propyl]Adenine (Tenofovir) to Newborn and Infant Rhesus Macaques. Antimicrob. Agents Chemother. 48: 1469-1487 [Abstract] [Full Text]  
  • White, K. L., Chen, J. M., Margot, N. A., Wrin, T., Petropoulos, C. J., Naeger, L. K., Swaminathan, S., Miller, M. D. (2004). Molecular Mechanisms of Tenofovir Resistance Conferred by Human Immunodeficiency Virus Type 1 Reverse Transcriptase Containing a Diserine Insertion after Residue 69 and Multiple Thymidine Analog-Associated Mutations. Antimicrob. Agents Chemother. 48: 992-1003 [Abstract] [Full Text]  
  • Magierowska, M., Bernardin, F., Garg, S., Staprans, S., Miller, M. D., Van Rompay, K. K. A., Delwart, E. L. (2004). Highly Uneven Distribution of Tenofovir-Selected Simian Immunodeficiency Virus in Different Anatomical Sites of Rhesus Macaques. J. Virol. 78: 2434-2444 [Abstract] [Full Text]  
  • Parkin, N. T., Hellmann, N. S., Whitcomb, J. M., Kiss, L., Chappey, C., Petropoulos, C. J. (2004). Natural Variation of Drug Susceptibility in Wild-Type Human Immunodeficiency Virus Type 1. Antimicrob. Agents Chemother. 48: 437-443 [Abstract] [Full Text]  
  • Wolf, K., Walter, H., Beerenwinkel, N., Keulen, W., Kaiser, R., Hoffmann, D., Lengauer, T., Selbig, J., Vandamme, A.-M., Korn, K., Schmidt, B. (2003). Tenofovir Resistance and Resensitization. Antimicrob. Agents Chemother. 47: 3478-3484 [Abstract] [Full Text]  
  • De Clercq, E. (2003). Clinical Potential of the Acyclic Nucleoside Phosphonates Cidofovir, Adefovir, and Tenofovir in Treatment of DNA Virus and Retrovirus Infections. Clin. Microbiol. Rev. 16: 569-596 [Abstract] [Full Text]  
  • Grim, S. A, Romanelli, F. (2003). Tenofovir Disoproxil Fumarate. The Annals of Pharmacotherapy 37: 849-859 [Abstract] [Full Text]  


Copyright © 2009 by the American Society for Microbiology.   For an alternate route to Journals.ASM.org, visit: http://intl-journals.asm.org | More Info»