PHARMACOKINETICS AND ANTIRETROVIRAL ACTIVITY OF LAMIVUDINE ALONE OR WHEN COADMINISTERED WITH ZIDOVUDINE IN HUMAN-IMMUNODEFICIENCY-VIRUS TYPE 1-INFECTED PREGNANT-WOMEN AND THEIR OFFSPRING

The safety, pharmacokinetics, and antiretroviral activity of lamivudin e alone and in combination with zidovudine was studied in pregnant wom en infected with human immunodeficiency virus type 1 (HIV-l) and their neonates, Women received the drugs orally from week 38 of pregnancy t o 1 week after delivery. Neonate therapy began 12 h after delivery and continued for 1 week, Both treatment regimens were well-tolerated in women and newborns. Lamivudine and zidovudine pharmacokinetics in preg nant women were similar to those in nonpregnant adults, Lamivudine and zidovudine freely crossed the placenta and were secreted in breast mi lk. Neonatal lamivudine clearance was about half that in pediatric pat ients; zidovudine clearance was consistent with previous reports. HIV- 1 RNA could be quantified in 17 of the 20 women, At the onset of labor /delivery, mean virus load had decreased by similar to 1.5 log(10) cop ies/mL in both treatment cohorts. Although not definitive for HIV-1 in fection status, all neonates had HIV-I RNA levels below the limit of q uantification at birth and at ages 1 and 2 weeks.