期刊
JAIDS-JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES
卷 52, 期 3, 页码 309-315出版社
LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1097/QAI.0b013e3181bca669
关键词
drug resistance mutations; etravirine; nonnucleoside reverse transcriptase inhibitors; pyrosequencing; quasispecies; reverse transcriptase
资金
- NIAID NIH HHS [R01 AI068581-01A1, AI46148, R01 AI068581, R01 AI046148, R56 AI068581, AI068581] Funding Source: Medline
Objectives: K103N, the most common nonnucleoside reverse transcriptase inhibitor (NNRTI)-resistant mutation in patients with transmitted resistance and in patients receiving a failing NNRTI-containing regimen, is fully susceptible to the new NNRTI, etravirine. Therefore, we sought to determine how often NNRTI-resistant Mutations other than K103N occur as minority variants in plasma samples for which standard genotypic resistance testing detects K103N alone. Methods: We performed ultradeep pyrosequencing (UDPS; 454 Life Sciences a Roche Company, Branford, CT) of plasma virus samples from 13 treatment-naive and 20 NNRTI-experienced patients in whom standard genotypic resistance testing revealed K103N but no other major NNRTI-resistance mutations. Results: Samples from 0 of 13 treatment-naive patients vs. 7 of 20 patients failing an NNRTI-containing regimen had minority variants with major etravirine-associated NNRTI-resistant mutations (P = 0.03, Fisher exact test): Y181C (7.0%), Y181C (3.6%) + G190A (3.2%), L1001 (14%), L100I (32%) + 190A (5.4%), K101E (3.8%) + G190A (4.9%), K101E (4.0%) + G190S (4.8%), and G190S (3.1%). Conclusions: In treatment-naive patients, UDPS did not detect additional major NNRTI-resistant mutations suggesting that etravirine may be effective in patients with transmitted K103N. In NNRTI-experienced patients, UDPS often detected additional major NNRTI-resistant mutations suggesting that etravirine may not be fully active in patients with acquired K103N.
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