Background:  Enfuvirtide (T20), a 36-amino acid peptide inhibitor of HIV-1 host cell membrane fusion, is the first of a new class of ART agents, the entry inhibitors. T20 is mainly used as a component of rescue treatment in multi-experienced HIV-infected patients because of no clinically significant interaction with concomitantly given drugs metabolized by CYP450 enzymes. The purpose of this study was to determine the maternal-fetal-placental transfer of T20 using an ex vivo human placental cotyledon perfusion model.

Methods:  Placentas obtained from uncomplicated full-term pregnancies were collected immediately after delivery. We perfused 3 isolated cotyledons according to the modified method described by Schneider et al, with human serum albumin (2 g/L) in Earles perfusate. Maternal perfusion comprised antipyrine 20 mg/L as internal control and T20 (90 mg/1250 mL). Antipyrine and T20 concentrations were determined by high-performance liquid chromatography (HPLC) coupled with spectrofluorimetry or ultraviolet detection with limit of quantitation of 50 ng/mL. Fetal transfer rate (ratio of fetal to maternal concentrations) and clearance index (ratio of T20 to antipyrine fetal transfer rate) were calculated.

Results:  In all 3 validated experiments, T20 was below the limit of quantitation in the fetal compartment. Concentrations measured in the maternal compartment were significantly above C_max (5.0 1.7 mg/L) with a mean of 12.4 mg/L (6.5 to 16.2 mg/L). Mean antipyrine fetal transfer rate was 36% (22 to 45%).

Conclusions:  Even at maternal concentrations twice above therapeutic levels, no transplacental passage of T20 was observed in the ex vivo human placental perfusion model. The high molecular weight and high protein binding of T20 (4492 kDa) may account for the lack of placental transfer. This result suggests that T-20 could be used in HIV-infected pregnant women without causing fetal exposure.