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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 pharmaco-kinetics, 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 (AUC0–12 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 Cmin, Cmax and AUC0–12 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•h/ml. The geometric means (90% CI) for ritonavir Cmin, Cmax and AUC0–12 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•h/ml. Age, weight, saquinavir dose per weight and body mass index differed significantly; saquinavir Cmin and AUC0–12 h 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 AUC0–12 h>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.