UC San Diego

OBJECTIVE: We evaluated the pharmacokinetics (pk) of raltegravir in HIV-infected women during pregnancy and postpartum. METHODS: IMPAACT 1026s is an on-going prospective study of antiretroviral pk during pregnancy (NCT00042289). Women receiving 400 mg raltegravir twice daily in combination antiretroviral therapy had intensive steady state 12-hour pk profiles performed during pregnancy and at 6-12 weeks postpartum. Targets were trough concentration above 0.035 μg/mL, the estimated tenth percentile in non-pregnant historical controls. RESULTS: Median raltegravir AUC was 6.6 μg*hr/mL for second trimester (n= 16), 5.4 μg*hr/mL for third trimester (n=41), and 11.6 μg*hr/mL postpartum (n= 38) (p=0.03 pp vs 2 trimester, p=0.001 pp vs third trimester). Trough concentrations were above the target in 69%, 80%, and 79% of second trimester, third trimester and postpartum subjects respectively, with wide variability ( < 0.010-0.917 μg/mL), and no significant difference between third trimester and postpartum trough concentrations was detected. The median ratio of cord blood/maternal raltegravir concentrations was 1.5. HIV RNA levels were < 400 copies/mL in 92% of women at delivery. Adverse events included elevated liver transaminases in one woman and vomiting in one. All infants with known status are HIV-uninfected. CONCLUSIONS: Median raltegravir AUC was reduced by approximately 50% during pregnancy; trough concentrations were frequently below target both during late pregnancy and postpartum. Raltegravir readily crossed the placenta. High rates of viral suppression at delivery and the lack of a clear relationship between raltegravir concentration and virologic effect in nonpregnant adults suggest that despite the decreased exposure during pregnancy, a higher dose is not necessary.