Polly Clayden, HIV i-Base

A prospective multicentre study conducted in Thailand, Spain, UK, Germany and the Netherlands evaluated the PK of RTV boosted SQV in HIV positive pregnant women.

Women in this study received SQV 500mg tablets + RTV, 1000/100mg BID + 2 NRTIs. They were enrolled either before the second (week 20, +2) or the 3rd trimester (week 33, +2). The study looked at safety, efficacy and 12 hour PK curves in the second and third trimester, and 4-6 weeks post-partum.

Forty women were enrolled, of these 8 discontinued the study before their first PK visit (2 due to toxicities associated with study drugs). The mean age of the women at baseline was 30.3 years, weight 68 kg, 42% of the women were ARV-naïve and 42% had viral load < 50 copies/mL.

Two serious adverse events were reported: one abortion and one diabetes gravidarum. AST/ALT grade 3/4 was reported in 2 women, lipids remained unchanged. At 20 and 33 weeks of gestation,
and 6 weeks postpartum, 73%, 91% and 87% of women had viral load <50 copies/mL respectively.

The investigators found the mean (SD) SQV AUC 0-12h, was 23.5 (11.9) mg/L.h, on week 20; 23.7 (9.1) mg/L.h, on week 33, and 25.0 (11.8) mg/L.h, on week 6 post partum. None of the women showed a subtherapeutic Cmin of SQV ( < 0.10 mg/L) at any timepoint. In this study SQV/r was safe and effective and plasma concentrations of SQV were not affected by pregnancy.

Ref: Van der Lugt J, Molto J, Hawkins D et al. Safety, efficacy and pharmacokinetics of saquinavir Boosted by ritonavir (1000/100mg BID) in pregnant HIV infected women. 48th ICAAC, 25-28 October 2008. Washington. Abstract H-455.