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Journal of Clinical Microbiology, March 2005, p. 1395-1400, Vol. 43, No. 3
0095-1137/05/$08.00+0     doi:10.1128/JCM.43.3.1395-1400.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

Diminished Replicative Fitness of Primary Human Immunodeficiency Virus Type 1 Isolates Harboring the K65R Mutation

Jan Weber,1 Bikram Chakraborty,1 Jitka Weberova,1 Michael D. Miller,2 and Miguel E. Quiñones-Mateu1,3*

Department of Molecular Genetics, Section Virology, Lerner Research Institute, Cleveland Clinic Foundation,1 Center for AIDS Research, Case Western Reserve University, Cleveland, Ohio,3 Gilead Sciences, Inc., Foster City, California2

Received 15 September 2004/ Returned for modification 9 November 2004/ Accepted 20 November 2004

The human immunodeficiency virus type 1 (HIV-1) reverse transcriptase (RT) resistance mutation K65R confers intermediate levels of resistance to several RT inhibitors, including a three- to fourfold reduction of tenofovir susceptibility. Here, we have used for the first time primary HIV-1 isolates from individuals who developed the K65R mutation while enrolled in a clinical trial of tenofovir to analyze the impact of this mutation on HIV-1 replicative fitness. A marked impairment in replicative fitness was observed in association with the selection of viruses carrying the K65R mutation in all patients. The mean replicative fitness among these viruses was 20% relative to the corresponding baseline wild-type virus, ranging from 10 to 32% depending on the accompanying RT mutations. These results support a reduction in in vivo replication for K65R mutant viruses.

* Corresponding author. Mailing address: Cleveland Clinic Foundation, Lerner Research Institute, Department of Molecular Genetics, Section Virology/NN10, 9500 Euclid Ave., Cleveland, OH 44195. Phone: (216) 444-2515. Fax: (216) 444-2998. E-mail: quinonm{at}ccf.org.

Journal of Clinical Microbiology, March 2005, p. 1395-1400, Vol. 43, No. 3
0095-1137/05/$08.00+0     doi:10.1128/JCM.43.3.1395-1400.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.



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