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(Referência obtida automaticamente do Web of Science, por meio da informação sobre o financiamento pela FAPESP e o número do processo correspondente, incluída na publicação pelos autores.)

High prevalence of HIV-1 transmitted drug-resistance mutations from proviral DNA massively parallel sequencing data of therapy-naive chronically infected Brazilian blood donors

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Autor(es):
Pessoa, Rodrigo [1] ; Sanabani, Sabri S. [1, 2]
Número total de Autores: 2
Afiliação do(s) autor(es):
[1] Univ Sao Paulo, Trop Med Inst Sao Paulo, Dept Dermatol, Lab Dermatol & Immunodeficiencies, Sao Paulo - Brazil
[2] Univ Sao Paulo, Sch Med, Hosp Clin, Dept Pathol, Clin Lab, Sao Paulo - Brazil
Número total de Afiliações: 2
Tipo de documento: Artigo Científico
Fonte: PLoS One; v. 12, n. 9 SEP 27 2017.
Citações Web of Science: 2
Resumo

Background An improved understanding of the prevalence of low-abundance transmitted drug-resistance mutations (TDRM) in therapy-naive 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 naive to antiretroviral drugs. Materials and methods 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. Results 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. Conclusion 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. (AU)

Processo FAPESP: 14/26983-3 - Sequenciamento em larga escala dos genomas do HIV na forma de RNA livre e DNA integrado: comparação entre os subtipos gerados, mutações relacionadas a resistência de drogas e o uso de co-receptores
Beneficiário:Sabri Saeed Mohamed Ahmed Al-Sanabani
Linha de fomento: Auxílio à Pesquisa - Regular
Processo FAPESP: 14/24596-2 - Sequenciamento em larga escala dos genomas do HIV na forma de RNA livre e DNA integrado: comparação entre os subtipos gerados, mutações relacionadas a resistência de drogas e o uso de co-receptores
Beneficiário:Rodrigo Pessoa de Farias
Linha de fomento: Bolsas no Brasil - Doutorado