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Minority HIV-1 Variants in Antiretroviral Naive Persons with Reverse Transcriptase Codon 215 Revertant Mutations.
J Virol. 2008 Aug 20;
Authors: Mitsuya Y, Varghese V, Wang C, Liu TF, Holmes SP, Jayakumar R, Gharizadeh B, Ronaghi M, Klein D, Fessel WJ, Shafer RW
T215 revertant mutations such as T215C/D/E/S that evolve from the nucleoside reverse transcriptase inhibitor mutations T215Y/F have been found in about 3% of HIV-1 isolates from newly diagnosed HIV-1 infected persons. We used a newly developed sequencing method - ultra-deep 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 form untreated persons containing T215 revertants ("revertant" samples) compared with samples from untreated persons lacking 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 F were 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 a T215 revertant in a subset of persons with T215 revertants.
PMID: 18715933 [PubMed - as supplied by publisher]
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Minority HIV-1 Variants in Antiretroviral Naive Persons with Reverse Transcriptase Codon 215 Revertant Mutations.
J Virol. 2008 Aug 20;
Authors: Mitsuya Y, Varghese V, Wang C, Liu TF, Holmes SP, Jayakumar R, Gharizadeh B, Ronaghi M, Klein D, Fessel WJ, Shafer RW
T215 revertant mutations such as T215C/D/E/S that evolve from the nucleoside reverse transcriptase inhibitor mutations T215Y/F have been found in about 3% of HIV-1 isolates from newly diagnosed HIV-1 infected persons. We used a newly developed sequencing method - ultra-deep 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 form untreated persons containing T215 revertants ("revertant" samples) compared with samples from untreated persons lacking 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 F were 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 a T215 revertant in a subset of persons with T215 revertants.
PMID: 18715933 [PubMed - as supplied by publisher]
More...