Longitudinal use of phenotypic resistance testing to HIV-1 protease inhibitors in patients developing HAART failure.
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 (> or = 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.
Servais
Jean
J
Laboratoire de Rétrovirologie, Centre de Recherche Public-Santé, Luxembourg, Luxembourg. jeanservais@hotmail.com
Plesséria
Jean-Marc
JM
Lambert
Christine
C
Fontaine
Elodie
E
Robert
Isabelle
I
Arendt
Vic
V
Staub
Thérèse
T
Schneider
François
F
Hemmer
Robert
R
Schmit
Jean-Claude
JC
D023241:Antiretroviral Therapy, Highly Active; D024882:Drug Resistance, Viral; D015658:HIV Infections / Q000188:drug therapy* / Q000821:virology; D017320:HIV Protease Inhibitors / Q000494:pharmacology*; D015497:HIV-1 / Q000187:drug effects*; D006801:Humans; D008137:Longitudinal Studies; D008826:Microbial Sensitivity Tests; D010641:Phenotype; D011237:Predictive Value of Tests; D017211:Treatment Failure
D017320:HIV Protease Inhibitors