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Collinearity of protease mutations in HIV-1 samples with high-level protease inhibitor class resistance
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2013 (English)In: Journal of Antimicrobial Chemotherapy, ISSN 0305-7453, E-ISSN 1460-2091, Vol. 68, no 2, 414-418 p.Article in journal (Refereed) Published
Abstract [en]

Objectives: To determine whether pan-protease inhibitor (PI)-resistant virus populations are composed predominantly of viruses with resistance to all PIs or of diverse virus populations with resistance to different subsets of PIs. Methods: We performed deep sequencing of plasma virus samples from nine patients with high-level genotypic and/or phenotypic resistance to all licensed PIs. The nine virus samples had a median of 12 PI resistance mutations by direct PCR Sanger sequencing. Results: For each of the nine virus samples, deep sequencing showed that each of the individual viruses within a sample contained nearly all of the mutations detected by Sanger sequencing. Indeed, a median of 94.9% of deep sequence reads had each of the PI resistance mutations present as a single chromatographic peak in the Sanger sequence. A median of 5.0% of reads had all but one of the Sanger mutations that were not part of an electrophoretic mixture. Conclusions: The collinearity of PI resistance mutations in the nine virus samples demonstrated that pan-PI-resistant viruses are able to replicate in vivo despite their highly mutated protease enzymes. We hypothesize that the marked collinearity of PI resistance mutations in pan-PI-resistant virus populations results from the unique requirements for multi-PI resistance and the extensive cross-resistance conferred by many of the accessory PI resistance mutations.

Place, publisher, year, edition, pages
2013. Vol. 68, no 2, 414-418 p.
Keyword [en]
Deep sequencing, Drug resistance, Minority variants, Sanger sequencing
National Category
Medical and Health Sciences
URN: urn:nbn:se:kth:diva-118314DOI: 10.1093/jac/dks409ISI: 000313652700025ScopusID: 2-s2.0-84872368503OAI: diva2:605708

QC 20130215

Available from: 2013-02-15 Created: 2013-02-14 Last updated: 2013-02-25Bibliographically approved

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