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

Abstract

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 (Cmin and Cmax), area under the plasma concentration-time curve (AUC0-12h), and total clearance (CLtotal) 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 [Cl]) for saquinavir Cmin, Cmax and AUC0-12h 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•h/ml. The geometric means (90% Cl) for ritonavir Cmin, Cmax and AUC0-12h 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•h/ml. Age, weight, saquinavir dose per weight and body mass index differed significantly; saquinavir Cmin and AUC0-12h were correlated with ritonavir Cmin 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 AUC0-12h>10,000 ng•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. © 2008 International Medical Press.