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- aggregation classification "A1".
- aggregation creator B504003.
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- aggregation creator person.
- aggregation date "2011".
- aggregation format "application/pdf".
- aggregation hasFormat 3226406.bibtex.
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- aggregation isPartOf urn:issn:0022-1899.
- aggregation language "eng".
- aggregation rights "I have transferred the copyright for this publication to the publisher".
- aggregation subject "Medicine and Health Sciences".
- aggregation title "A376S in the connection subdomain of HIV-1 reverse transcriptase confers increased risk of virological failure to nevirapine therapy".
- aggregation abstract "Background. The clinical relevance of mutations in the connection subdomain and the ribonuclease ( RNase) H domain of HIV-1 reverse transcriptase (RT) is uncertain. Methods. The risk of virological failure to nonnucleoside RT inhibitor (NNRTI)-based antiretroviral therapy (ART) was evaluated in NNRTI-naive patients who started NNRTIs in the EuroSIDA study after July 1997 according to preexisting substitutions in the connection subdomain and the RNase H domain of HIV-1 RT. An observed association between A376S and virological failure was further investigated by testing in vitro NNRTI susceptibility of single site-directed mutants and patient-derived recombinant viruses. Enzymatic assays also determined the effects of A376S on nevirapine and template-primer binding to HIV-1 RT. Results. Virological failure occurred in 142 of 287 (49%) individuals: 77 receiving nevirapine (67%) and 65 receiving efavirenz (38%) (P < .001). Preexisting A376S was associated with an increased risk of virological failure to nevirapine (relative hazard [RH] = 10.4; 95% confidence interval [CI], 2.0-54.7), but it did not affect efavirenz outcome the same way (RH = 0.5; 95% CI, 0.1-2.2) (P value for interaction = .013). A376S conferred selective low-level nevirapine resistance in vitro, and led to greater affinity for double-stranded DNA. Conclusions. The A376S substitution in the connection subdomain of HIV-1 RT causes selective nevirapine resistance and confers an increased risk of virological failure to nevirapine-based ART.".
- aggregation authorList BK844662.
- aggregation endPage "752".
- aggregation issue "5".
- aggregation startPage "741".
- aggregation volume "204".
- aggregation aggregates 3232457.
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