Background: Initial results of PACTG 386 demonstrated inadequate Saquinavir-SCG (SQV) exposure when SQV was dosed at 1200 mg TID to pregnant women. Therefore, the PK and safety of a low-dose Ritonavir (RTV)-boosted SQV regimen (800 mg SQV/100 mg RTV given BID), were evaluated. Preliminary results of the maternal and infant outcomes of this Phase I, open label, dose evaluating trial are presented.

Methods: HIV-1 infected pregnant women received SQV-SGC (800 mg po bid) and RTV (100 mg po bid) antepartum [AP], intrapartum [IP] and postpartum [PP] with Zidovudine (ZDV) and Lamivudine (3TC); infants received ZDV/3TC for 6 wks. Blood samples for determination of SQV in plasma were collected after 2 wks of therapy, at delivery and 6 wks post-partum. HIV viral load was analyzed using Roche Amplicor Ultrasensitive Assay; CD4/CD8 using ACTG consensus panel; and viral culture using the DAIDS ACTG standard assay. Hematology and chemistry parameters were evaluated at intervals.

Results: Thirteen (13) mother-infant pairs were enrolled; PK evaluations were completed AP on 13 women, IP on 6 and PP on 9 women. Mean age and gestational age (GA) at entry was 28 yrs and 23 wks, respectively. The mean GA for PK was 27 wks. Mean entry HIV RNA was 13,385 copies (3.75 Log¹⁰). All mothers had < 400 HIV RNA copies at delivery. The mean CD4 count at entry and delivery was 299 and 526 cells/mm³, respectively. All subjects exceeded the target SQV AUC₂₄. Toxicities were reported for 6 infants and 3 mothers. The most common toxicities for infants were anemia (3/12) and neutropenia (2/12). One (1) mother had a grade 2 elevation in liver enzymes, resulting in drug discontinuation, another had a grade 3 elevated amylase, and another had a grade 3 elevation in blood sugar. Placental passage of SQV-SGC/RTV was assessed in 8 maternal/infant pairs. Four (4) of 8 infants had detectable SQV and 1 had detectable RTV levels. Mean GA at delivery was 38 wks with a 50% Cesarean Section rate. None of the 6 infants tested after 4 months (mos) of age was infected; 6 infants are less than 4 mos old.

Conclusions: 1) SQV with low-dose RTV boosting given BID in combination with ZDV/3TC was well tolerated by women during pregnancy, labor, and postpartum. Infant toxicity was limited to hematological parameters which are likely due to ZDV; 2) SQV, with low-dose RTV, achieves good exposure and crosses the placenta at very low levels; and 3) all mothers had undetectable HIV RNA levels before delivery, and so far, no infants have been HIV-infected.