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- Title
Susceptibility of HIV-1 Subtypes B9, CRF07BC and CRF01AE that Are Predominantly Circulating in China to HIV-1 Entry Inhibitors.
- Authors
Xiaoling Yu; Lin Yuan; Yang Huang; Weisi Xu; Zhiming Fang; Shuwen Liu; Yiming Shao; Shibo Jiang; Liying Ma
- Abstract
Background: The B9, CRF07BC and CRF01AE are the predominant HIV-1 subtypes in China. It is essential to determine their baseline susceptibility to HIV entry inhibitors before these drugs are used in China. Methodology/Principal Findings: The baseline susceptibility of 14 representative HIV-1 isolates (5 CRF07BC, 4 CRF01AE, and 5 B9), most of which were R5 viruses, obtained from drug-naïve patients to HIV entry inhibitors, including two fusion inhibitors (enfuvirtide and C34), two CCR5 antagonists (maraviroc and TAK779) and one CXCR4 antagonist (AMD3100), were determined by virus inhibition assay. The sequences of their env genes were amplified and analyzed. These isolates possessed similar susceptibility to C34, but they exhibited different sensitivity to enfuvirtide, maraviroc or TAK779. CRF07BC isolates, which carried polymorphisms of A578T and V583I in the N-terminal heptad repeat and E630Q, E662A, K665S, A667K and S668N in the C-terminal heptad repeat of gp41, were about 5-fold less sensitive than B9 and CRF01AE isolates to enfuvirtide. Subtype B9 isolates with a unique polymorphism site of F317W in V3 loop, were about 4- to 5-fold more sensitive than CRF07BC and CRF01AE isolates to maraviroc and TAK779. AMD3100 at the concentration as high as 5 μM exhibited no significant inhibitory activity against any of the isolates tested. Conclusion: Our results suggest that there are significant differences in baseline susceptibility to HIV entry inhibitors among the predominant HIV-1 subtypes in China and the differences may partly result from the naturally occurring polymorphisms in these subtypes. This study provides useful information for rational design of optimal therapeutic regimens for HIV-1- infected patients in China.
- Subjects
CHINA; HIV; HIV-positive persons; ENFUVIRTIDE (Drug); MARAVIROC (Drug); GENETIC polymorphisms
- Publication
PLoS ONE, 2011, Vol 6, Issue 3, p1
- ISSN
1932-6203
- Publication type
Article
- DOI
10.1371/journal.pone.0017605