Enfuvirtide

Mechanism (as reported)

A study reported that HIV entry begins with gp120 attachment to host CD4 and chemokine receptor sites, followed by gp41 conformational change that enables fusion. Enfuvirtide was described as a synthetic peptide that binds to the gp41 subunit, preventing the conformational change required for membrane fusion. (PMIDs: 12457443, 14664654, 15148534)

Key findings (each cites a source)

• A study described enfuvirtide as the first drug of a new class of antiretroviral medications known as fusion inhibitors that blocks fusion between the virus particle and host target cell by binding to gp41 and preventing the conformational change needed for membrane fusion. [PMID 12457443]
• Research reported that viral entry involves gp120 attachment to CD4 and chemokine receptor sites followed by gp41 conformational change enabling fusion, and that enfuvirtide binds gp41 to block fusion of viral and cellular membranes. [PMID 12457443, 14664654]
• A phase I clinical trial of intravenous enfuvirtide was reported to show a substantial decline in HIV plasma viral load in the highest dose group and no serious adverse effects. [PMID 12457443]
• Phase II trials were reported to evaluate continuous subcutaneous infusions versus intermittent subcutaneous injections; intermittent injections were described as pharmacokinetically superior and associated with fewer administration difficulties. [PMID 12457443]
• A study reported that in some subjects where enfuvirtide monotherapy was added to an already failing regimen, viral load reduction appeared short-lived, suggesting resistance development. [PMID 12457443]
• Two large randomised clinical trials were reported to show a significant virological advantage for optimised background plus enfuvirtide compared with optimised background alone at 24 weeks. [PMID 12457443]
• Research reported that enfuvirtide plus optimised background significantly reduced plasma HIV RNA levels compared with optimised background alone after 24 weeks and that antiviral efficacy was maintained to 48 weeks in two randomised trials in adults with advanced HIV infection. [PMID 14664654]
• A study reported that at 24 and 48 weeks, the increase from baseline in CD4+ cell count was significantly greater in the enfuvirtide plus optimised background group than in the optimised background alone group. [PMID 14664654]
• A small pediatric trial was reported in which enfuvirtide (30 mg/m2 or 60 mg/m2) in combination with other antiretroviral agents reduced plasma HIV RNA levels and increased CD4+ cell counts. [PMID 14664654]
• A study reported that local injection-site reactions were common with enfuvirtide use. [PMID 12457443, 14664654, 15219553]
• A study reported that lymphadenopathy and pneumonia occurred more often in patients receiving enfuvirtide plus optimised background than in the control group. [PMID 14664654]
• A laboratory study reported that HIV isolates with reduced susceptibility to enfuvirtide have been recovered from patients receiving enfuvirtide in combination with other antiretroviral agents. [PMID 14664654]