Reduced atazanavir exposure has been demonstrated during pregnancy with standard atazanavir/ritonavir dosing. We studied an increased dose during the third trimester of pregnancy.
IMPAACT 1026s is a prospective, non-blinded pharmacokinetic study of HIV-infected pregnant women taking antiretrovirals for clinical indications, including two cohorts (with or without tenofovir) receiving atazanavir/ritonavir 300/100 mg once daily during the 2nd trimester (2nd trim), 400/100 mg during the 3rd trimester (3rd trim) and 300/100 mg postpartum (PP). Intensive steady-state 24-hour pharmacokinetic profiles were performed. Atazanavir concentrations were measured by HPLC. Pharmacokinetic targets were the 10th percentile atazanavir AUC (29.4 mcg*hr/mL) in non-pregnant adults on standard dose and 0.15 mcg/mL, minimum trough concentration.
Atazanavir pharmacokinetic data were available for 37 women without tenofovir, 35 with tenofovir; Median (range) pharmacokinetic parameters are presented for 2nd, 3rd trim and PP and number who met target/total. * indicates p<0.05 compared to PP.
Atazanavir without tenofovir
AUC 30.5 (9.19–93.8), 45.7 (11–88.3), and 48.8 (9.9–112.2) mcg-hr/mL, and 8/14, 29/37 and 27/34 met target. C24h was 0.49 (0.09–4.09), 0.71 (0.14–2.09), and 0.90 (0.05–2.73) mcg/mL; 13/14, 36/37 and 29/34 met target.
Atazanavir with tenofovir
AUC 26.2 (6.8–60.9)*, 37.7 (0.72–88.2)*, and 58.6 (6–149) mcg-hr/mL, and 7/17, 23/32 and 27/29 met target. C24h was 0.44 (0.12–1.06)*, 0.57 (0.02–2.06)*, and 1.26 (0.09–5.43) mcg/mL; 7/17, 23/32 and 27/29 met target. Atazanavir/ritonavir was well tolerated with no unanticipated adverse events.
Atazanavir/ritonavir increased to 400/100mg provides adequate atazanavir exposure during the third trimester and should be considered during the second trimester.