Side by side

1. 1.Binds the HR1 region of HIV gp41 as the virus engages CD4 and a co-receptor.
2. 2.Prevents the conformational change that drives fusion of viral and cell membranes.
3. 3.Blocks entry, so the virus never gets into the cell.
4. 4.Acts outside the cell, independently of reverse transcriptase or protease.
5. 5.Resistance arises through changes in the gp41 HR1 sequence.

• Treatment-experienced HIV-1 infection as part of combination therapy (TORO 1 and TORO 2)
• Fusion-inhibition mechanism research
• Salvage regimens before newer classes existed

• Greater viral load reduction and CD4 gain than optimised background therapy alone at 48 weeks in TORO
• Injection-site reactions in nearly all patients
• No oral formulation - twice-daily subcutaneous injections are a large burden
• Bacterial pneumonia occurred more often than in controls

• Injection-site nodules, pain and erythema in almost everyone
• Bacterial pneumonia
• Hypersensitivity, including a rare hypersensitivity reaction on rechallenge
• Diarrhoea and nausea
• Insomnia and depression
• Raised eosinophils

Research context only - a specialist HIV medicine. Licensed dosing is 90 mg subcutaneously twice daily into the abdomen, thigh or upper arm, rotating sites; the TORO trials ran 48 weeks with viral load below 400 copies and CD4 change as endpoints. It is only used within a fully suppressive combination regimen.

Research context only