Abstract
Entry inhibitors represent a new class of antiretroviral agents for the treatment of infection with HIV-1. While resistance to other HIV drug classes has been well described, resistance to this new class is still ill defined despite considerable clinical use. Several potential mechanisms have been proposed: tropism switching (utilization of CXCR4 instead of CCR5 for entry), increased affinity for the coreceptor, increased rate of virus entry into host cells, and utilization of inhibitor-bound receptor for entry. In this review we will address the development of attachment, fusion, and coreceptor entry inhibitors and explore recent studies describing potential mechanisms of resistance.
Highlights
Entry inhibitors represent a new class of antiretroviral agents for the treatment of infection with HIV-1
HIV-1 entry inhibitors fall into three major classes based on the specific entry process that they target: 1) attachment inhibitors, which block the interaction between HIV-1 envelope and CD4, 2) coreceptor inhibitors, which block the interaction between HIV-1 envelope and chemokine receptor 5 (CCR5) or C-XC chemokine receptor 4 (CXCR4), and 3) fusion inhibitors, which prevent the virus from mixing its membrane with the host cell membrane and releasing the viral core into the cytoplasm (Table 2)
To further support this hypothesis, maraviroc resistant viruses that were susceptible to aplaviroc were unable to be inhibited by aplaviroc in the presence of high concentrations of maraviroc
Summary
The major approach to the medical management of HIV infection is the treatment of patients with antiviral drugs. Due to the high rates of virus production and the mutation rate of the virus [1], treatment of HIV-1 infection generally includes administration of three agents in combination, referred to as highly active antiretroviral therapy (HAART). Sustained treatment of patients with three active drugs results in suppression of viral replication in peripheral blood to below detection limits of sensitive clinical assays (
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