Genotypic correlates of resistance to HIV-1 protease inhibitors on longitudinal data: The role of secondary mutations

Jean Servais*, Jean Marc Plesséria, Christine Lambert, Elodie Fontaine, Isabelle Robert, Vic Arendt, Thérèse Staub, François Schneider, Robert Hemmer, Jean Claude Schmit

*Corresponding author for this work

Research output: Contribution to journalArticleResearchpeer-review

15 Citations (Scopus)

Abstract

Direct sequencing of the pol gene was assessed retrospectively with protease inhibitor susceptibility in a longitudinal study. A total of 134 samples from 26 patients were analysed at regular intervals up to 2 years. Patients were included in virological failure despite indinavir, ritonavir or saquinavir based triple-drug therapy. Both the type and number of certain secondary protease mutations modulated the effect of primary mutations on phenotypic resistance. This was notably applicable to L101/V, and to lesser extents to A71V/T. However, combinations of primary mutations, including 154V could predict resistance to the drug used and nelfinavir in more than 80%. In contrast, in vitro cross-resistance to amprenavir was rarely encountered. In addition, there was a relationship between a higher number of key mutations and poorer virological and clinical outcomes, respectively, from 6 and 3 months on. The key mutations were the protease mutations independently conferring phenotypic resistance and/or the reverse transcriptase mutations predicting treatment outcome. This relationship was independent from drug history, viral load and CD4 cell count measurements. In summary, even on a small sample size, sequence-based genotyping seems to be a good prognostic marker when performed longitudinally. In the context of primary resistance mutations, including additional secondary mutations, it may be useful in the prediction of phenotypic and clinical resistance. This should be assessed to optimize treatment monitoring before emergence of broadly cross-resistant virus.

Original languageEnglish
Pages (from-to)239-248
Number of pages10
JournalAntiviral Therapy
Volume6
Issue number4
Publication statusPublished - 2001

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