LL-37
The only human cathelicidin, a 37-amino-acid antimicrobial and immune-signalling peptide. Extensively studied as a molecule; barely studied as a therapy.
Immune & Inflammation
Enfuvirtide
The first HIV fusion inhibitor, approved in 2003. A 36-amino-acid peptide that blocks the virus from entering cells, now reserved for multidrug-resistant infection.
Overview
Most HIV drugs act after the virus is already inside a cell. Enfuvirtide acts before that. When HIV attaches to a cell, a viral protein called gp41 folds in on itself like a spring to pull the virus and cell membranes together. Enfuvirtide is a copy of one arm of that spring, and it jams the mechanism by binding where the other arm should go. The fusion never completes and the virus cannot get in.
A 36-amino-acid synthetic peptide corresponding to the HR2 region of HIV-1 gp41. Binds the HR1 groove of gp41 during the fusion intermediate state, preventing formation of the six-helix bundle required to appose viral and cellular membranes. Activity is HIV-1 specific and independent of coreceptor tropism. Resistance arises through mutations in the HR1 gp41 region, particularly residues 36-45, and emerges relatively readily with functional monotherapy. TORO 1 and TORO 2 established efficacy in treatment-experienced patients. Use has declined substantially with the availability of newer oral agents.
Research areas
HIVViral fusionMultidrug-resistant infection
Dosing reported in the literature
Every protocol below is reproduced from a published study or approved labelling, with its source named. These are records of what was studied — not recommendations, and not a suggestion that any of them is appropriate for any person.
| Protocol as reported | Source |
|---|---|
| 90 mg subcutaneously twice daily in combination with other antiretroviral agentsNever used as monotherapy — resistance emerges rapidly. | Approved product labelling |
| Enfuvirtide added to an optimised background regimen in treatment-experienced adults over 48 weeks | TORO 1 and TORO 2, New England Journal of Medicine 2003 |
Trial status
Phase 3 TORO 1 and TORO 2 completed and published; approved 2003.
Reported safety signals
- Injection-site reactions occur in almost everyone treated and are the dominant reason for discontinuation.
- An increased rate of bacterial pneumonia was observed in the trials.
- Hypersensitivity reactions have been reported and can recur on rechallenge.
- Requires twice-daily injection indefinitely, which is why oral alternatives displaced it where available.
Common questions
Why is enfuvirtide barely used now?
It requires two subcutaneous injections every day for life, and nearly everyone develops injection-site reactions. Once integrase inhibitors and other oral options became available for resistant HIV, there was little reason to accept that burden.
Primary sources
Medical disclaimer
This page is for informational and research purposes only. Nothing here constitutes medical advice. The compounds discussed are research chemicals. Consult a qualified clinician before starting any protocol.
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