710   Cord Blood Protease Inhibitor (PI) Concentrations in Infants Born to Mothers Receiving PIs.

M. Mirochnick*¹, A. Dorenbaum², B. Cunningham-Schrader³, C. Cunningham⁴, R. Gelber⁵, L. Mofenson⁶, and J. Sullivan⁷.
¹Boston Univ. Sch. of Med., Boston, MA;²Chiron Corp, Emeryville, CA;³FSTRF, Amherst, NY;⁴SUNY Hlth. Sci. Ctr., Syracuse, NY;⁵SDAC/ Harvard Sch. of Publ. Health, Boston, MA;⁶NICHD, Rockville, MD; and⁷Univ. of Massachusetts Med. Sch., Worcester, MA.

Background:Although the use of protease inhibitors during pregnancy is growing, few data are available describing PI concentrations in cord blood after their use in pregnancy.

Methods:PI concentrations were measured in cord blood plasma samples obtained at delivery from women enrolled in PACTG 316 (a prospective, randomized, double-blind, placebo-controlled trial of peripartum nevirapine vs. placebo added to standard antiretroviral therapy) who had a cord blood sample collected and were receiving a combination antiretroviral regimen including at least 1 protease inhibitor at the time of delivery. PI concentrations were assayed by HPLC, with a lower limit of detection of 0.1—0.15mg/ml, depending on the PI.

Results:Adequate samples were collected from 68 HIV-infected pregnant women (average age = 27.2+5.3 yrs; ethnicity: 42 black, 16 Hispanic, 9 white, 1 unknown). Thirty-eight women received nelfinavir (NFV), 21 received indinavir (IDV), 8 received saquinavir (SQV) and 6 received ritonavir (RTV). Four women received more than one protease inhibitor. The last maternal dose before delivery was administered a median of 12.2 hours (range: 0.67—40.9) before delivery in 26 women for whom the time of the last dose was available. PI concentrations were undetectable in 53 (78%) of the cord blood samples. Of the 15 women with a detectable cord blood PI concentration, 14 were receiving NFV (median concentration = 0.35mg/ml; range: 0.10—0.61mg/ml), and 1 was receiving RTV (0.38mg/ml).

Conclusions:Cord blood PI concentrations are extremely low after maternal PI treatment during pregnancy. Low cord blood PI concentrations may reflect lack of maternal PI dosing during labor, poor maternal PI absorption and/or poor placental PI transfer, and they make it unlikely that maternal PI use provides post- exposure prophylaxis to the infant immediately after birth.