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

✍ Scribed by Jean Servais; Jean-Marc Plesséria; Christine Lambert; Elodie Fontaine; Isabelle Robert; Vic Arendt; Thérèse Staub; François Schneider; Robert Hemmer; Jean-Claude Schmit

• Publisher: John Wiley and Sons
• Year: 2002
• Tongue: English
• Weight: 90 KB
• Volume: 67
• Category: Article
• ISSN: 0146-6615
• DOI: 10.1002/jmv.10076

✦ Synopsis

Abstract

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. J. Med Virol. 67:312–319, 2002. © 2002 Wiley‐Liss, Inc.