Currently, there is a growing interest in using entry inhibitors to treat HIV-2-infected patients because, among the available drugs, few are fully active against HIV-2. Recent studies indicate that maraviroc and other experimental entry inhibitors, including new CCR5 and CXCR4 antagonists, inhibit primary isolates of HIV-2 as well as HIV-1 and may, therefore, expand the existing therapeutic armamentarium against HIV-2. There are, however, significant differences between the evolution of HIV-1 and HIV-2 envelope glycoproteins during infection that can lead to differences in the response to therapy with entry inhibitors over the course of the infection. Here, we review the available data on the susceptibility of HIV-2 to entry inhibitors in the context of the evolution of the sequence, structure, and function of envelope glycoproteins during infection.
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