Longitudinal use of phenotypic resistance testing to HIV-1 protease inhibitors in patients developing HAART failure

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

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3 Citations (Scopus)


An "in-house" recombinant virus protease inhibitor susceptibility assay was carried out (median of 3 per patient) retrospectively in 26 patients failing HIV protease inhibitor based therapy at regular intervals to the initiation of the first protease inhibitor. Patients were treated with either indinavir (N=6), ritonavir (N=10), or saquinavir (N = 10) and two nucleoside analogues. Second line therapy was based on single or dual protease inhibitor regimens occasionally containing nelfinavir. Clinically relevant resistance cut-offs associated with a poorer virological outcome from 6 months on and the clinical outcome from 3 months on were determined tentatively as 4- to 8-fold resistance for indinavir and ritonavir and 2.5- to 8-fold to saquinavir. In addition, the degree of cross-resistance at the time of the change of protease inhibitor was associated with the response in viral load at 6 months to the second line therapy (P=0.018). Cross-resistance (>=8-fold) between ritonavir and indinavir was common (78 and 100%). Cross-resistance between indinavir or ritonavir and saquinavir was less frequent (75 and 60% respectively) than the opposite (100%, P=0.004). Cross-resistance to nelfinavir was encountered more frequently(> 70%) than to amprenavir (9%). The magnitudes of resistance were correlated between each other. In summary, the protease inhibitor susceptibility carried out longitudinally appears to be an earlier prognostic marker than viral load in a context of cross-resistance. The magnitude of resistance, as a marker of cross-resistance, should be useful to guide second line therapy.

Original languageEnglish
Pages (from-to)312-319
Number of pages8
JournalJournal of Medical Virology
Issue number3
Publication statusPublished - 2002


  • HAART failure
  • HIV
  • Phenotypic resistance
  • Protease inhibitors


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