Author(s):
Borrego, Pedro 
; Calado, Rita ; Marcelino, José M ; Bártolo, Inês ; Rocha, Cheila ; Cavaco-Silva, Patrícia ; Doroana, Manuela ; Antunes, Francisco ; Maltez, Fernando ; Caixas, Umbelina ; Barroso, Helena ; Taveira, Nuno
Date: 2012
Origin: Repositório Comum
Subject(s): HIV-2; inhibitors
Description
Background: The baseline susceptibility of primary
HIV-2 to maraviroc (MVC) and other entry inhibitors is
currently unknown. Methods: The susceptibility of 19 HIV-2 isolates obtained
from asymptomatic and AIDS patients and seven HIV-1
clinical isolates to the fusion inhibitors enfuvirtide (ENF)
and T-1249, and to the coreceptor antagonists AMD3100,
TAK-779 and MVC, was measured using a TZM-bl cellbased
assay. The 50% inhibitory concentration (IC50), 90%
inhibitory concentration (IC90) and dose–response curve
slopes were determined for each drug. on HIV-2 than on HIV-1 (211- and 2-fold, respectively).
AMD3100 and TAK-779 inhibited HIV-2 and HIV-1 CXCR4
tropic (X4) and CCR5 tropic (R5) variants with similar IC50
and IC90 values. MVC, however, inhibited the replication
of R5 HIV-2 variants with significantly higher IC90 values
(42.7 versus 9.7 nM; P<0.0001) and lower slope values
(0.7 versus 1.3; P<0.0001) than HIV-1. HIV-2 R5 variants
derived from AIDS patients were significantly less sensitive
to MVC than variants from asymptomatic patients,
this being inversely correlated with the absolute number
of CD4+ T-cells. Conclusions: T-1249 is a potent inhibitor of HIV-2 replication
indicating that new fusion inhibitors might be useful
to treat HIV-2 infection. Coreceptor antagonists TAK-
779 and AMD3100 are also potent inhibitors of HIV-2
replication. The reduced sensitivity of R5 variants to MVC,
especially in severely immunodeficient patients, indicates
that the treatment of HIV-2-infected patients with MVC
might require higher dosages than those used in HIV-1
patients, and should be adjusted to the disease stage.
