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HIV-1 entry inhibitors: an overview Kuritzkes DRCurr Opin HIV AIDS 2009[Mar]; 4 (2): 82-7PURPOSE OF REVIEW: To provide an overview of HIV-1 entry inhibitors, with a focus on chemokine receptor antagonists. RECENT FINDINGS: Entry of HIV-1 into target cells is an ordered multistep process involving attachment, co-receptor binding, and fusion. Inhibitors of each step have been identified and shown to have antiviral activity in clinical trials. Phase 1-2 trials of monoclonal antibodies and small-molecule attachment inhibitors have demonstrated activity in HIV-1-infected patients, but none has progressed to later-phase clinical trials. The postattachment inhibitor ibalizumab has shown activity in phase 1 and 2 trials; further studies are anticipated. The CCR5 antagonists maraviroc (now been approved for clinical use) and vicriviroc (in phase 3 trials) have shown significant benefit in controlled trials in treatment-experienced patients; additional CCR5 antagonists are in various stages of clinical development. Targeting CXCR4 has proven to be more challenging. Although proof of concept has been demonstrated in phase 1-2 trials of two compounds, neither proved suitable for chronic administration. Little progress has been reported in developing longer acting or orally bioavailable fusion inhibitors. SUMMARY: A CCR5 antagonist and a fusion inhibitor are approved for use as HIV-1 entry inhibitors. Development of drugs targeting other steps in HIV-1 entry is ongoing.|Anti-HIV Agents/*pharmacology[MESH]|CCR5 Receptor Antagonists[MESH]|Clinical Trials as Topic[MESH]|HIV Fusion Inhibitors/*pharmacology[MESH]|HIV Infections/*drug therapy[MESH]|HIV-1/*drug effects[MESH]|Humans[MESH]|Receptors, CXCR4/antagonists & inhibitors[MESH]|Receptors, HIV/*antagonists & inhibitors[MESH] |
