High prevalence of HIV-1 transmitted drug-resistance mutations from proviral DNA massively parallel sequencing data of therapy-naïve chronically infected Brazilian blood donors.
An improved understanding of the prevalence of low-abundance transmitted drug-resistance mutations (TDRM) in therapy-naïve HIV-1-infected patients may help determine which patients are the best candidates for therapy. In this study, we aimed to obtain a comprehensive picture of the evolving HIV-1 TD...
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2017-01-01
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| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC5617215?pdf=render |
| _version_ | 1819264226007449600 |
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| author | Rodrigo Pessôa Sabri S Sanabani |
| author_facet | Rodrigo Pessôa Sabri S Sanabani |
| author_sort | Rodrigo Pessôa |
| collection | DOAJ |
| description | An improved understanding of the prevalence of low-abundance transmitted drug-resistance mutations (TDRM) in therapy-naïve HIV-1-infected patients may help determine which patients are the best candidates for therapy. In this study, we aimed to obtain a comprehensive picture of the evolving HIV-1 TDRM across the massive parallel sequences (MPS) of the viral entire proviral genome in a well-characterized Brazilian blood donor naïve to antiretroviral drugs.The MPS data from 128 samples used in the analysis were sourced from Brazilian blood donors and were previously classified by less-sensitive (LS) or "detuned" enzyme immunoassay as non-recent or longstanding HIV-1 infections. The Stanford HIV Resistance Database (HIVDBv 6.2) and IAS-USA mutation lists were used to interpret the pattern of drug resistance. The minority variants with TDRM were identified using a threshold of ≥ 1.0% and ≤ 20% of the reads sequenced. The rate of TDRM in the MPS data of the proviral genome were compared with the corresponding published consensus sequences of their plasma viruses.No TDRM were detected in the integrase or envelope regions. The overall prevalence of TDRM in the protease (PR) and reverse transcriptase (RT) regions of the HIV-1 pol gene was 44.5% (57/128), including any mutations to the nucleoside analogue reverse transcriptase inhibitors (NRTI) and non-nucleoside analogue reverse transcriptase inhibitors (NNRTI). Of the 57 subjects, 43 (75.4%) harbored a minority variant containing at least one clinically relevant TDRM. Among the 43 subjects, 33 (76.7%) had detectable minority resistant variants to NRTIs, 6 (13.9%) to NNRTIs, and 16 (37.2%) to PR inhibitors. The comparison of viral sequences in both sources, plasma and cells, would have detected 48 DNA provirus disclosed TDRM by MPS previously missed by plasma bulk analysis.Our findings revealed a high prevalence of TDRM found in this group, as the use of MPS drastically increased the detection of these mutations. Sequencing proviral DNA provided additional information about TDRM, which may impact treatment decisions. The overall results emphasize the importance of continuous monitoring. |
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| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-23T20:26:07Z |
| publishDate | 2017-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-0a3e87e412e04a44a23a8948edc478d02022-12-21T17:32:22ZengPublic Library of Science (PLoS)PLoS ONE1932-62032017-01-01129e018555910.1371/journal.pone.0185559High prevalence of HIV-1 transmitted drug-resistance mutations from proviral DNA massively parallel sequencing data of therapy-naïve chronically infected Brazilian blood donors.Rodrigo PessôaSabri S SanabaniAn improved understanding of the prevalence of low-abundance transmitted drug-resistance mutations (TDRM) in therapy-naïve HIV-1-infected patients may help determine which patients are the best candidates for therapy. In this study, we aimed to obtain a comprehensive picture of the evolving HIV-1 TDRM across the massive parallel sequences (MPS) of the viral entire proviral genome in a well-characterized Brazilian blood donor naïve to antiretroviral drugs.The MPS data from 128 samples used in the analysis were sourced from Brazilian blood donors and were previously classified by less-sensitive (LS) or "detuned" enzyme immunoassay as non-recent or longstanding HIV-1 infections. The Stanford HIV Resistance Database (HIVDBv 6.2) and IAS-USA mutation lists were used to interpret the pattern of drug resistance. The minority variants with TDRM were identified using a threshold of ≥ 1.0% and ≤ 20% of the reads sequenced. The rate of TDRM in the MPS data of the proviral genome were compared with the corresponding published consensus sequences of their plasma viruses.No TDRM were detected in the integrase or envelope regions. The overall prevalence of TDRM in the protease (PR) and reverse transcriptase (RT) regions of the HIV-1 pol gene was 44.5% (57/128), including any mutations to the nucleoside analogue reverse transcriptase inhibitors (NRTI) and non-nucleoside analogue reverse transcriptase inhibitors (NNRTI). Of the 57 subjects, 43 (75.4%) harbored a minority variant containing at least one clinically relevant TDRM. Among the 43 subjects, 33 (76.7%) had detectable minority resistant variants to NRTIs, 6 (13.9%) to NNRTIs, and 16 (37.2%) to PR inhibitors. The comparison of viral sequences in both sources, plasma and cells, would have detected 48 DNA provirus disclosed TDRM by MPS previously missed by plasma bulk analysis.Our findings revealed a high prevalence of TDRM found in this group, as the use of MPS drastically increased the detection of these mutations. Sequencing proviral DNA provided additional information about TDRM, which may impact treatment decisions. The overall results emphasize the importance of continuous monitoring.http://europepmc.org/articles/PMC5617215?pdf=render |
| spellingShingle | Rodrigo Pessôa Sabri S Sanabani High prevalence of HIV-1 transmitted drug-resistance mutations from proviral DNA massively parallel sequencing data of therapy-naïve chronically infected Brazilian blood donors. PLoS ONE |
| title | High prevalence of HIV-1 transmitted drug-resistance mutations from proviral DNA massively parallel sequencing data of therapy-naïve chronically infected Brazilian blood donors. |
| title_full | High prevalence of HIV-1 transmitted drug-resistance mutations from proviral DNA massively parallel sequencing data of therapy-naïve chronically infected Brazilian blood donors. |
| title_fullStr | High prevalence of HIV-1 transmitted drug-resistance mutations from proviral DNA massively parallel sequencing data of therapy-naïve chronically infected Brazilian blood donors. |
| title_full_unstemmed | High prevalence of HIV-1 transmitted drug-resistance mutations from proviral DNA massively parallel sequencing data of therapy-naïve chronically infected Brazilian blood donors. |
| title_short | High prevalence of HIV-1 transmitted drug-resistance mutations from proviral DNA massively parallel sequencing data of therapy-naïve chronically infected Brazilian blood donors. |
| title_sort | high prevalence of hiv 1 transmitted drug resistance mutations from proviral dna massively parallel sequencing data of therapy naive chronically infected brazilian blood donors |
| url | http://europepmc.org/articles/PMC5617215?pdf=render |
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