Long-lasting protection of activity of nucleoside reverse transcriptase inhibitors and protease inhibitors (PIs) by boosted PI containing regimens
Data(s) |
2012
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Resumo |
Background The accumulation of mutations after long-lasting exposure to a failing combination antiretroviral therapy (cART) is problematic and severely reduces the options for further successful treatments. Methods We studied patients from the Swiss HIV Cohort Study who failed cART with nucleoside reverse transcriptase inhibitors (NRTIs) and either a ritonavir-boosted PI (PI/r) or a non-nucleoside reverse transcriptase inhibitor (NNRTI). The loss of genotypic activity <3, 3–6, >6 months after virological failure was analyzed with Stanford algorithm. Risk factors associated with early emergence of drug resistance mutations (<6 months after failure) were identified with multivariable logistic regression. Results Ninety-nine genotypic resistance tests from PI/r-treated and 129 from NNRTI-treated patients were analyzed. The risk of losing the activity of ≥1 NRTIs was lower among PI/r- compared to NNRTI-treated individuals <3, 3–6, and >6 months after failure: 8.8% vs. 38.2% (p = 0.009), 7.1% vs. 46.9% (p<0.001) and 18.9% vs. 60.9% (p<0.001). The percentages of patients who have lost PI/r activity were 2.9%, 3.6% and 5.4% <3, 3–6, >6 months after failure compared to 41.2%, 49.0% and 63.0% of those who have lost NNRTI activity (all p<0.001). The risk to accumulate an early NRTI mutation was strongly associated with NNRTI-containing cART (adjusted odds ratio: 13.3 (95% CI: 4.1–42.8), p<0.001). Conclusions The loss of activity of PIs and NRTIs was low among patients treated with PI/r, even after long-lasting exposure to a failing cART. Thus, more options remain for second-line therapy. This finding is potentially of high relevance, in particular for settings with poor or lacking virological monitoring. |
Formato |
application/pdf |
Identificador |
http://boris.unibe.ch/14861/1/journal.pone.0050307.pdf Scherrer, Alexandra U.; Böni, Jürg; Yerly, Sabine; Klimkait, Thomas; Aubert, Vincent; Furrer, Hansjakob; Calmy, Alexandra; Cavassini, Matthias; Elzi, Luigia; Vernazza, Pietro L.; Bernasconi, Enos; Ledergerber, Bruno; Günthard, Huldrych F.; Swiss HIV Cohort Study (SHCS), (2012). Long-lasting protection of activity of nucleoside reverse transcriptase inhibitors and protease inhibitors (PIs) by boosted PI containing regimens. PLoS ONE, 7(11), e50307. Lawrence, Kans.: Public Library of Science 10.1371/journal.pone.0050307 <http://dx.doi.org/10.1371/journal.pone.0050307> doi:10.7892/boris.14861 info:doi:10.1371/journal.pone.0050307 info:pmid:23189194 urn:issn:1932-6203 |
Idioma(s) |
eng |
Publicador |
Public Library of Science |
Relação |
http://boris.unibe.ch/14861/ |
Direitos |
info:eu-repo/semantics/openAccess |
Fonte |
Scherrer, Alexandra U.; Böni, Jürg; Yerly, Sabine; Klimkait, Thomas; Aubert, Vincent; Furrer, Hansjakob; Calmy, Alexandra; Cavassini, Matthias; Elzi, Luigia; Vernazza, Pietro L.; Bernasconi, Enos; Ledergerber, Bruno; Günthard, Huldrych F.; Swiss HIV Cohort Study (SHCS), (2012). Long-lasting protection of activity of nucleoside reverse transcriptase inhibitors and protease inhibitors (PIs) by boosted PI containing regimens. PLoS ONE, 7(11), e50307. Lawrence, Kans.: Public Library of Science 10.1371/journal.pone.0050307 <http://dx.doi.org/10.1371/journal.pone.0050307> |
Tipo |
info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion PeerReviewed |