title: Minority human immunodeficiency virus type 1 variants in antiretroviral-naive persons with reverse transcriptase codon 215 revertant mutations.
abstract: T215 revertant mutations such as T215C/D/E/S that evolve from the nucleoside reverse transcriptase (RT) inhibitor mutations T215Y/F have been found in about 3% of human immunodeficiency virus type 1 (HIV-1) isolates from newly diagnosed HIV-1-infected persons. We used a newly developed sequencing method-ultradeep pyrosequencing (UDPS; 454 Life Sciences)--to determine the frequency with which T215Y/F or other RT inhibitor resistance mutations could be detected as minority variants in samples from untreated persons that contain T215 revertants ("revertant" samples) compared with samples from untreated persons that lack such revertants ("control" samples). Among the 22 revertant and 29 control samples, UDPS detected a mean of 3.8 and 4.8 additional RT amino acid mutations, respectively. In 6 of 22 (27%) revertant samples and in 4 of 29 control samples (14%; P = 0.4), UDPS detected one or more RT inhibitor resistance mutations. T215Y or T215F was not detected in any of the revertant or control samples; however, 4 of 22 revertant samples had one or more T215 revertants that were detected by UDPS but not by direct PCR sequencing. The failure to detect viruses with T215Y/F in the 22 revertant samples in this study may result from the overwhelming replacement of transmitted T215Y variants by the more fit T215 revertants or from the primary transmission of a T215 revertant in a subset of persons with T215 revertants.
authors: Department of Medicine, Division of Infectious Diseases, Stanford University Medical Center, Stanford, California 94305, USA.
authors: Yumi
authors: Y
authors: Mitsuya
authors: Vici
authors: V
authors: Varghese
authors: Chunlin
authors: C
authors: Wang
authors: Tommy F
authors: TF
authors: Liu
authors: Susan P
authors: SP
authors: Holmes
authors: Prerana
authors: P
authors: Jayakumar
authors: Baback
authors: B
authors: Gharizadeh
authors: Mostafa
authors: M
authors: Ronaghi
authors: Daniel
authors: D
authors: Klein
authors: W Jeffrey
authors: WJ
authors: Fessel
authors: Robert W
authors: RW
authors: Shafer
mesh_terms: D044966:Anti-Retroviral Agents / Q000627:therapeutic use; D018791:CD4 Lymphocyte Count; D003062:Codon; D024882:Drug Resistance, Viral; D015658:HIV Infections / Q000188:drug therapy / Q000821:virology*; D054303:HIV Reverse Transcriptase / Q000235:genetics*; D015497:HIV-1 / Q000145:classification / Q000235:genetics* / Q000302:isolation & purification; D006801:Humans; D020125:Mutation, Missense; D017422:Sequence Analysis, DNA / Q000379:methods*; D013489:Suppression, Genetic; D019562:Viral Load
chemical_list: D044966:Anti-Retroviral Agents; D003062:Codon; C514824:reverse transcriptase, Human immunodeficiency virus 1; D054303:HIV Reverse Transcriptase