HIV-1 Entry Inhibitor Resistance

Abstract

Purpose of review: This review discusses resistance to HIVentry inhibitors with a focus on currently approved drugs and future uses.Recent findings: The HIV entry inhibitor class is unique among HIV antiretrovirals as it encompasses drugs that target the different stages of the HIV entry cascade. There are currently 2 FDA-approved drugs in this class, the chemokine receptor-5 (CCR5) antagonist maraviroc (MVC) and the fusion inhibitor enfuvirtide (T-20). Attachment inhibitors are still under development, with multiple candidates in various states of development. Coreceptor antagonists are the most widely studied because patients who lack CCR5 are protected from HIV infection. CXCR4-antagonist development has proceeded more cautiously, due to limited antiviral effect in clinical trials. Fusion inhibitor development is advancing slowly, with the majority of research focusing on orally available small-molecule inhibitors. Resistance to these subclasses manifests in a complex manner and does not conform to the resistance paradigm of other antiretroviral classes.Summary: This review will describe this heterogeneous class of antiretrovirals and the unique challenges and opportunities that they present in the pursuit of improving options for treatment.