Pharmacokinetics, safety and efficacy of saquinavir/ ritonavir 1,000/100 mg twice daily as HIV type-1 therapy and transmission prophylaxis in pregnancy.

Background: A saquinavir/ritonavir-containing regimen is one option for the prevention of mother-to-child transmission of HIV during pregnancy. We evaluated the pharmacokinetics, efficacy and safety of saquinavir/ritonavir 1,000/100 mg twice daily plus nucleos(t)ide reverse transcriptase inhibitors in 13 women during late pregnancy and compared the results to those of 15 non-pregnant women.

Methods: Protease inhibitor plasma concentration profiles were assessed at 12 h using a standardized therapeutic drug monitoring procedure and measured by LC-MS/MS. Minimum and maximum concentrations (C(min) and C(max)), area under the plasma concentration-time curve (AUC(0-12 h)), and total clearance (CL(total)) were compared between the groups and correlated to demographic, physiological and clinical cofactors. Antiviral and immunological efficacy and safety were investigated.

Results: The geometric means (90% confidence interval [CI]) for saquinavir C(min), C(max) and AUC(0-2 h) of pregnant versus non-pregnant women were 572 (437-717) versus 765 (485-1,052, P = 0.064) ng/ml, 2,168 (1,594-2,807) versus 3,344 (2,429-4,350; P = 0.045) ng/ml and 15,512 (11,657-19,943) versus 24,027 (17,454-31,548, P = 0.029) ng x h/ml. The geometric means (90% CI) for ritonavir C(min), C(max) and AUC(0+12 h) were 190 (148-234) versus 310 (240-381, P = 0.011) ng/ml, 781 (580-999) versus 1,552 (1,127-2,007, P = 0.004) ng/ml and 5,576 (4,303-7,006) versus 10,528 (8,131-13,177, P = 0.003) ng x h/ml. Age, weight, saquinavir dose per weight and body mass index differed significantly; saquinavir C(min) and AUC(0-12 h) were correlated with ritonavir C(min) and saquinavir dose per weight. After a mean of 11 weeks treatment, 12 of 13 pregnant women had a viral load < 400 copies/ml, which was similar to the results of non-pregnant women.

Conclusions: Although saquinavir plasma concentrations were significantly lower in pregnant women compared with non-pregnant women, all pregnant women displayed a saquinavir AUC(0-12 h) > 10,000 ng x h/ml, 92.3% had a viral load < 400 copies/ml at birth. Saquinavir was well tolerated by the mothers and all newborn children were HIV type-1 negative at 18 months of age.