Journal
CURRENT OPINION IN HIV AND AIDS
Volume 4, Issue 2, Pages 82-87Publisher
LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1097/COH.0b013e328322402e
Keywords
attachment; chemokine receptor antagonist; fusion inhibitor; HIV-1 envelope
Categories
Funding
- NIH [R37 AI053357, K24 RR016482, U01AI068836]
- GlaxoSmithKline
- Human Genome Sciences
- Monogram Biosciences
- Pfizer
- Schering-Plough
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Purpose 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.
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