Maraviroc Pharmacokinetics in HIV-1-Infected Pregnant Women

Abstract

Objective: To describe the pharmacokinetics of maraviroc in human immunodeficiency virus (HIV)-infected women during pregnancy and post partum.

Methods: HIV-infected pregnant women receiving maraviroc as part of clinical care had intensive steady-state 12-hour pharmacokinetic profiles performed during the third trimester and ≥2 weeks after delivery. Cord blood samples and matching maternal blood samples were taken at delivery. The data were collected in 2 studies: P1026 (United States) and PANNA (Europe). Pharmacokinetic parameters were calculated.

Results: Eighteen women were included in the analysis. Most women (12; 67%) received 150 mg of maraviroc twice daily with a protease inhibitor, 2 (11%) received 300 mg twice daily without a protease inhibitor, and 4 (22%) had an alternative regimen. The geometric mean ratios for third-trimester versus postpartum maraviroc were 0.72 (90% confidence interval, .60-.88) for the area under the curve over a dosing interval (AUCtau) and 0.70 (0.58-0.85) for the maximum maraviroc concentration. Only 1 patient showed a trough concentration (Ctrough) below the suggested target of 50 ng/mL, both during pregnancy and post partum. The median ratio of maraviroc cord blood to maternal blood was 0.33 (range, 0.03-0.56). The viral load close to delivery was <50 copies/mL in 13 women (76%). All children were HIV negative at testing.

Conclusions: Overall maraviroc exposure during pregnancy was decreased, with a reduction in AUCtau and maximum concentration of about 30%. Ctrough was reduced by 15% but exceeded the minimum Ctrough target concentration. Therefore, the standard adult dose seems sufficient in pregnancy.

Clinical trials registration: NCT00825929 and NCT000422890.

Trial registration: ClinicalTrials.gov NCT00422890 NCT00825929 NCT00422890 NCT00825929.

Keywords: HIV; MTCT; maraviroc; pharmacokinetics; pregnancy.

Figure 1.

Mean concentration-time profiles for maraviroc (150 mg twice daily with protease inhibitor) during pregnancy (third trimester) and post partum. Values represent mean maraviroc concentrations at steady state (with standard deviations); reference concentrations (dashed line) are from Kakuda et al [16].

Figure 2.

Individual ratios of third-trimester to postpartum values for maraviroc area under the curve (AUC) (A) and concentration at the last time point (C_last) (B), by dosing regimen. For the 150-mg regimen, the medians are shown (line). Abbreviations: BID, twice daily; PI, protease inhibitor; QD, once daily.