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Antimicrobial Agents and Chemotherapy, November 2009, p. 4869-4878, Vol. 53, No. 11
0066-4804/09/$08.00+0     doi:10.1128/AAC.00592-09
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

Nonpolymorphic Human Immunodeficiency Virus Type 1 Protease and Reverse Transcriptase Treatment-Selected Mutations{triangledown}

Rajin Shahriar,1 Soo-Yon Rhee,1 Tommy F. Liu,1 W. Jeffrey Fessel,2 Anthony Scarsella,3 William Towner,4 Susan P. Holmes,5 Andrew R. Zolopa,1 and Robert W. Shafer1*

Division of Infectious Diseases, Department of Medicine, Stanford University, Stanford, California,1 Clinical Trials Unit, Kaiser Permanente Medical Care Program, San Francisco, California,2 Pacific Oaks Medical Group, Beverly Hills, California,3 Kaiser Permanente Medical Care Program, Los Angeles, California,4 Department of Statistics, Stanford University, Stanford, California5

Received 1 May 2009/ Returned for modification 4 June 2009/ Accepted 19 August 2009

The spectrum of human immunodeficiency virus type 1 (HIV-1) protease and reverse transcriptase (RT) mutations selected by antiretroviral (ARV) drugs requires ongoing reassessment as ARV treatment patterns evolve and increasing numbers of protease and RT sequences of different viral subtypes are published. Accordingly, we compared the prevalences of protease and RT mutations in HIV-1 group M sequences from individuals with and without a history of previous treatment with protease inhibitors (PIs) or RT inhibitors (RTIs). Mutations in protease sequences from 26,888 individuals and in RT sequences from 25,695 individuals were classified according to whether they were nonpolymorphic in untreated individuals and whether their prevalence increased fivefold with ARV therapy. This analysis showed that 88 PI-selected and 122 RTI-selected nonpolymorphic mutations had a prevalence that was fivefold higher in individuals receiving ARVs than in ARV-naïve individuals. This was an increase of 47% and 77%, respectively, compared with the 60 PI- and 69 RTI-selected mutations identified in a similar analysis that we published in 2005 using subtype B sequences obtained from one-fourth as many individuals. In conclusion, many nonpolymorphic mutations in protease and RT are under ARV selection pressure. The spectrum of treatment-selected mutations is changing as data for more individuals are collected, treatment exposures change, and the number of available sequences from non-subtype B viruses increases.

* Corresponding author. Mailing address: Division of Infectious Diseases, Department of Medicine, Stanford University, Room S-169, Stanford, CA 94305. Phone: (650) 725-2946. Fax: (650) 725-2088. E-mail: rshafer{at}stanford.edu

{triangledown} Published ahead of print on 31 August 2009.

Antimicrobial Agents and Chemotherapy, November 2009, p. 4869-4878, Vol. 53, No. 11
0066-4804/09/$08.00+0     doi:10.1128/AAC.00592-09
Copyright © 2009, American Society for Microbiology. All Rights Reserved.





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