Background: Human Immunodeficiency Virus (HIV) entry inhibitors target the first step of the HIV life
cycle and efficiently inhibit HIV from infecting the immune cells which is a key prerequisite for viral spread. Because
of their unique mechanism of action on cell-cell transmission, they may provide a promising perspective for
the treatment of AIDS.
Method: Maraviroc (MVC) and Enfuvirtide (ENF) have been approved by the FDA for the treatment of HIV-1
infection. Attachment inhibitors (BMS-663068 and TNX-355) and co-receptor inhibitors (PRO-140 and cenicriviroc
(CVC)) have reached phase II or III clinical trials. These entry inhibitors show beneficial pharmacokinetics and
substantial reductions of plasma HIV-1 RNA load in HIV infected patients.
Results: Most entry inhibitors are generally safe, without serious Adverse Event (AE) or AE leading to discontinuation.
The pharmacokinetics of MVC, CVC and BMS-663068 was affected by CYP3A4 inhibitors or inducers. The
FDA has proposed that the dosage of MVC (300 mg, BID, orally) be adjusted to half or two-fold for patients if it is
combined with a major CYP3A4 inhibitor or inducer, respectively. Researchers suggested that the dosage of CVC
(50-75 mg, QD, orally) may also need adjustment but the dosage of BMS-663068 (600 mg, BID, orally) does not.
Conclusion: The standard, recommended ENF dosage is 90 mg BID, injected subcutaneously for adults, and 2
mg/kg BID, up to a maximum dose of 90 mg, injected subcutaneously for pediatric patients. TNX-355 (10-15
mg/kg, BID, intravenously) and PRO-140(5-10 mg/kg, BID, intravenously; 324 mg, biweekly, subcutaneously) are
administered by intravenous infusion or subcutaneous injection.