000			03162na a2200241 4500
003			PC2268
005			20180417112244.0
008			130622s2011 xxx||||| |||| 00| 0 eng d
024			_a10.1371/journal.pone.0019461
040			_cH12O
041			_aeng
100			_91016 _aDelgado Vázquez, Rafael _eMicrobiología y Parasitología
245	0	0	_aAdded value of deep sequencing relative to population sequencing in heavily pre-treated HIV-1-infected subjects _h[artículo]
260			_bPLoS One, _c2011.
300			_a6(5):e19461.
500			_aFormato Vancouver: Codoñer FM, Pou C, Thielen A, García F, Delgado R, Dalmau D, et al. Added value of deep sequencing relative to population sequencing in heavily pre-treated HIV-1-infected subjects. PLoS One. 2011;6(5):e19461.
501			_aPMID: 21602929
504			_aContiene 25 referencias.
520			_aObjective: To explore the potential of deep HIV-1 sequencing for adding clinically relevant information relative to viral population sequencing in heavily pre-treated HIV-1-infected subjects. Methods: In a proof-of-concept study, deep sequencing was compared to population sequencing in HIV-1-infected individuals with previous triple-class virological failure who also developed virologic failure to deep salvage therapy including, at least, darunavir, tipranavir, etravirine or raltegravir. Viral susceptibility was inferred before salvage therapy initiation and at virological failure using deep and population sequencing genotypes interpreted with the HIVdb, Rega and ANRS algorithms. The threshold level for mutant detection with deep sequencing was 1%. Results: 7 subjects with previous exposure to a median of 15 antiretrovirals during a median of 13 years were included. Deep salvage therapy included darunavir, tipranavir, etravirine or raltegravir in 4, 2, 2 and 5 subjects, respectively. Self-reported treatment adherence was adequate in 4 and partial in 2; one individual underwent treatment interruption during follow-up. Deep sequencing detected all mutations found by population sequencing and identified additional resistance mutations in all but one individual, predominantly after virological failure to deep salvage therapy. Additional genotypic information led to consistent decreases in predicted susceptibility to etravirine, efavirenz, nucleoside reverse transcriptase inhibitors and indinavir in 2, 1, 2 and 1 subject, respectively. Deep sequencing data did not consistently modify the susceptibility predictions achieved with population sequencing for darunavir, tipranavir or raltegravir. Conclusions: In this subset of heavily pre-treated individuals, deep sequencing improved the assessment of genotypic resistance to etravirine, but did not consistently provide additional information on darunavir, tipranavir or raltegravir susceptibility. These data may inform the design of future studies addressing the clinical value of minority drug-resistant variants in treatment-experienced subjects.
710			_981 _aServicio de Microbiología y Parasitología
856			_uhttp://pc-h12o-es.m-hdoct.a17.csinet.es/pdf/pc/2/pc2268.pdf _ySolicitar documento
942			_2ddc _cART _n0
999			_c2268 _d2268