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 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 (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_{0–12 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 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•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•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.