Minority Human Immunodeficiency Virus Type 1 Variants in Antiretroviral-Naive Persons with Reverse Transcriptase Codon 215 Revertant Mutations

被引:62
作者
Mitsuya, Yumi
Varghese, Vici
Wang, Chunlin
Liu, Tommy F.
Holmes, Susan P. [2 ]
Jayakumar, Prerana
Gharizadeh, Baback [3 ]
Ronaghi, Mostafa [3 ]
Klein, Daniel [4 ]
Fessel, W. Jeffrey [4 ]
Shafer, Robert W. [1 ]
机构
[1] Stanford Univ, Med Ctr, Div Infect Dis, Dept Med, Stanford, CA 94305 USA
[2] Stanford Univ, Dept Stat, Stanford, CA 94305 USA
[3] Stanford Univ, Stanford Genome Technol Ctr, Stanford, CA 94305 USA
[4] Kaiser Permanente Med Care Program No Calif, Oakland, CA USA
关键词
D O I
10.1128/JVI.01827-07
中图分类号
Q93 [微生物学];
学科分类号
071005 ; 100705 ;
摘要
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.
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页码:10747 / 10755
页数:9
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