期刊
PLOS ONE
卷 7, 期 11, 页码 -出版社
PUBLIC LIBRARY SCIENCE
DOI: 10.1371/journal.pone.0050307
关键词
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资金
- Swiss HIV Cohort Study
- Swiss National Science Foundation (SNF) [33CS30-134277]
- SNF [3247B0-112594, 324730-130865]
- SHCS [470, 528, 569, 683]
- SHCS Research Foundation
- European Community under the Collaborative HIV and Anti-HIV Drug Resistance Network (CHAIN) [FP7/2007-2013, 223131]
- Union Bank of Switzerland
- Tibotec, Switzerland
- Gilead, Switzerland
- Roche
- Abbott
- Bristol-Myers Squibb
- GlaxoSmithKline
- Gilead
- Tibotec
- Merck Sharp Dohme
- GSK
- MSD
- Pfizer
- Janssen
- ViiV
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.
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