Minority Variants Associated with Transmitted and Acquired HIV-1 Nonnucleoside Reverse Transcriptase Inhibitor Resistance: Implications for the Use of Second-Generation Nonnucleoside Reverse Transcriptase Inhibitors
2009 (English)In: Journal of Acquired Immune Deficiency Syndromes, ISSN 1525-4135, E-ISSN 1944-7884, Vol. 52, no 3, 309-315 p.Article in journal (Refereed) Published
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.
Place, publisher, year, edition, pages
2009. Vol. 52, no 3, 309-315 p.
drug resistance mutations, etravirine, nonnucleoside reverse transcriptase inhibitors, pyrosequencing, quasispecies, reverse transcriptase
IdentifiersURN: urn:nbn:se:kth:diva-159898DOI: 10.1097/QAI.0b013e3181bca669ISI: 000271202900002PubMedID: 19734799ScopusID: 2-s2.0-7035053455OAI: oai:DiVA.org:kth-159898DiVA: diva2:787641
QC 201502112015-02-112015-02-112015-02-11Bibliographically approved