title: Diminished replicative fitness of primary human immunodeficiency virus type 1 isolates harboring the K65R mutation.
abstract: 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.
authors.affiliation: Cleveland Clinic Foundation, Lerner Research Institute, Department of Molecular Genetics, Section Virology/NN10, 9500 Euclid Ave., Cleveland, OH 44195, USA.
authors.forename: Jan
authors.initials: J
authors.lastname: Weber
authors.forename: Bikram
authors.initials: B
authors.lastname: Chakraborty
authors.forename: Jitka
authors.initials: J
authors.lastname: Weberova
authors.forename: Michael D
authors.initials: MD
authors.lastname: Miller
authors.forename: Miguel E
authors.initials: ME
authors.lastname: Quiñones-Mateu
mesh_terms: D000163:Acquired Immunodeficiency Syndrome / Q000188:drug therapy; D001483:Base Sequence; D024882:Drug Resistance, Viral; D054303:HIV Reverse Transcriptase / Q000235:genetics*; D015497:HIV-1 / Q000187:drug effects / Q000235:genetics* / Q000502:physiology; D006801:Humans; D008969:Molecular Sequence Data; D009154:Mutation; D014779:Virus Replication
chemical_list: D054303:HIV Reverse Transcriptase