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Phenotypic Susceptibility in vitro to Amprenavir, Atazanavir, Darunavir, Lopinavir, and Tipranavir of HIV-2 Clinical Isolates from the French ANRS HIV-2 Cohort
D Desbois1, G Peytavin1, S Matheron1, F Damond1, G Collin1, A Bénard2, P Campa3, G Chêne2, F Brun-Vézinet1, Diane Descamps*1, and The French ANRS HIV-2 Cohort (ANRS CO 05 VIH-2)
1Hosp Bichat-Claude Bernard, Paris, France; 2INSERM U593, Bordeaux, France; and 3Hosp St Antoine, Paris, France
Background:
Few studies have reported
phenotypic susceptibilities of HIV-2 isolates to ART drugs. The aim of this
study was to determine the in vitro
susceptibility to 5 protease inhibitors
(PI) of HIV-2 clinical isolates collected from naïve and PI-experienced
patients.
Methods: Phenotypic susceptibilities to amprenavir (APV), atazanavir
(ATV), darunavir (DRV), lopinavir
(LPV), and tipranavir (TPV) were evaluated using the
ANRS peripheral blood mononuclear cell (PBMC) method in co-cultivated isolates
obtained from ROD HIV-2 reference strain and from 9 PI-naïve HIV-2-infected
patients. Among these 9 patients, 7 had received PI-containing HAART (indinavir, ritonavir, saquinavir, or nelfinavir) for a
median of 29 months (range 13 to 60) and had available co-cultured supernatants
before and after PI initiation. For these latter patients IC50
values were compared before (T0) and after the selection of PI mutations (T1). IC50
values of BRU HIV-1 reference strain were also determined using the same
methodology adapted for HIV-1 and compared to those obtained in HIV-2.
Results: Median IC50 of the 9 HIV-2 wild type
isolates and of the ROD reference strain were: 551 nM (340 to 880)
for APV, 51 nM (32 to 170) for ATV, 4 nM (2 to 11) for DRV, 31 nM (22
to 56) for LPV, and 352 nM (275 to 420) for TPV. DRV
and LPV shared similar IC50 for both HIV-1 and HIV-2 wild type
viruses. By contrast, HIV-2 wild type isolates showed an increase in IC50
of 7-fold for ATV and TPV and 30-fold for APV compared to HIV-1. Among
the 7 PI-treated patients, I82F/V, I84V, and L90M substitutions, described as
primary PI mutations for HIV-1, were present at T1, alone or in association together
or with other secondary substitutions such as L10I, V33I, I54M, V71I. In these patients, compared to T0, IC50 at
T1 showed a 4- to >10-fold increase for all tested PI.
Conclusions: In HIV-2 wild type isolates, IC50
to APV, ATV, and TPV were higher than HIV-1, raising the hypothesis of a lower
activity of these PI in HIV-2-infected patients. Substitutions in the protease
gene at positions 82, 84, and 90 affected the phenotypic susceptibility to APV,
ATV, DRV, LPV, and TPV. These phenotypic
susceptibility results ask the question of which PI could be or could not be
recommended in HIV-2 patients initiating HAART.
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