In a setting in which the rate of mother-to-child HBV transmission was low with the administration of hepatitis B immune globulin and hepatitis B vaccine in infants born to HBeAg-positive mothers, the additional maternal use of TDF did not result in a significantly lower rate of transmission. (Funded by the Eunice Kennedy Shriver National Institute of Child Health and Human Development; ClinicalTrials.gov number, NCT01745822 .).

Background The impact of pregnancy on efavirenz pharmacokinetics is unknown. Methods International Maternal Pediatric Adolescent AIDS Clinical Trials (IMPAACT) P1026s is an on-going, prospective, non-blinded study of antiretroviral pharmacokinetics in HIV-infected pregnant women that included a cohort receiving 600 mg efavirenz once daily as part of combination antiretroviral therapy. Intensive steady-state 24-hour blood sampling was performed during the third trimester and at 6–12 weeks postpartum. Maternal and umbilical cord blood samples were drawn at delivery. Pharmacokinetics targets were the estimated 10th percentile efavirenz AUC in non-pregnant historical controls (40.0 mcg.hr/mL) and a trough concentration of 1 mcg/mL. Results Twenty five women were enrolled during the third trimester: median (range) age was 29.3 (18.9–42.9) years, weight 69.0 (40–130) kg, gestational age 32.9 (30.1–38.7) weeks. Median (range) efavirenz AUC0-24, Cmax and C24hour were 55.4 mcg.hr/mL (13.5–220.3), 5.4 mcg/mL (1.9–12.2) and 1.6 mcg/ml (0.23–8.13), respectively. Efavirenz AUC and Cmax did not differ during pregnancy and postpartum but C24hour was lower during the third trimester (1.6 vs. 2.1 mcg/mL, p=0.01). During the third trimester, 5 of 25 (20%) women had an efavirenz AUC below the target and 3 of 25 (12%) had a trough concentration below 1 mcg/mL. Efavirenz cord blood/maternal concentration ratio was 0.49 (0.37–0.74). All women had a HIV-1 RNA viral load less than 400 copies/mL at delivery and 19 (76%) had a viral load below 50 copies/mL. One child was perinatally HIV-infected. Three women were exposed to efavirenz throughout the first 6 weeks of pregnancy. EFV was well tolerated and among the 25 infants no congenital anomalies or newborn complications were reported. Conclusions Changes in efavirenz pharmacokinetics during pregnancy compared to postpartum are not sufficiently large enough to warrant a dose adjustment during pregnancy.

Background Although antiretroviral regimens containing integrase inhibitors rapidly suppress HIV viral load in non-pregnant adults, few published data from randomised controlled trials have compared the safety and efficacy of any integrase inhibitor to efavirenz when initiated during pregnancy. We compared safety and efficacy of antiretroviral therapy with either raltegravir or efavirenz in late pregnancy.Methods An open-label, randomised controlled trial was done at 19 hospitals and clinics in Argentina,

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AIMTo describe the pharmacokinetics and safety of indinavir boosted with ritonavir (IDV/r) during the second and third trimesters of pregnancy and in the post-partum period. METHODSIMPAACT P1026s is an on-going, prospective, non-blinded study of antiretroviral pharmacokinetics (PK) in HIV-infected pregnant women with a Thai cohort receiving IDV/r 400/100 mg twice daily during pregnancy through to 6-12 weeks post-partum as part of clinical care. Steady-state PK profiles were performed during the second (optional) and third trimesters and at 6-12 weeks post-partum. PK targets were the estimated 10 th percentile IDV AUC (12.9 mg ml -1 h) in non-pregnant historical Thai adults and a trough concentration of 0.1 mg ml -1 , the suggested minimum target. RESULTSTwenty-six pregnant women were enrolled; thirteen entered during the second trimester. Median (range) age was 29.8 (18.9-40.8) years and weight 60.5 (50.0-85.0) kg at the third trimester PK visit. The 90% confidence limits for the geometric mean ratio of the indinavir AUC(0,12 h) and Cmax during the second trimester and post-partum (ante : post ratios) were 0.58 (0.49, 0.68) and 0.73 (0.59, 0.91), respectively; third trimester/post-partum AUC(0,12 h) and Cmax ratios were 0.60 (0.53, 0.68) and 0.63 (0.55, 0.72), respectively. IDV/r was well tolerated and 21/26 women had a HIV-1 viral load < 40 copies ml -1 at delivery. All 26 infants were confirmed HIV negative. CONCLUSIONIndinavir exposure during the second and third trimesters was significantly reduced compared with post-partum and~30% of women failed to achieve a target trough concentration. Increasing the dose of IDV/r during pregnancy to 600/100 mg twice daily may be preferable to ensure adequate drug concentrations. WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT• Highly active antiretroviral therapy (HAART) is recommended during pregnancy for HIV/AIDS treatment and/or the prevention of mother-to-child transmission of HIV.• Physiological changes during pregnancy can reduce antirerotivral drug exposure.• Indinavir trough concentrations have been reported to be reduced during the third trimester of pregnancy following an indinavir/ritonavir dose of 400/100 mg twice daily. However, indinavir and ritonavir exposures have not been fully characterized during the second and third trimesters of pregnancy and in the early post-partum period. WHAT THIS STUDY ADDS• Median indinavir exposures during the second and third trimesters were significantly reduced compared with post-partum.• Approximately 30% of women failed to achieve a target trough concentration during the third trimester.• Indinavir and ritonavir were tolerated well during pregnancy and an increased dose of indinavir during pregnancy may be preferable to ensure adequate exposure throughout pregnancy.