We report a case of therapeutic drug monitoring guided raltegravir use for the prevention of vertical HIV transmission in a premature neonate born to a woman living with perinatally acquired HIV and documented resistance to multiple HIV drugs. Maternal viral load was above 1,000 copies/ml at delivery. This case demonstrates delayed raltegravir elimination in a neonate born at 33 weeks gestational age and a need for less frequent raltegravir dosing than is used in older infants and children.

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... n living with perinatally acquired HIV often have complex antiretroviral (ARV) drug resistance profiles [1]. In such cases, it can be challenging to select ARVs for the prevention of vertical HIV transmission (PVT) when a woman is not virologically suppressed at delivery. The advent of integrase inhibitors provides an additional ARV class to consider in the setting of multidrug resistant HIV. Raltegravir, the first marketed integrase inhibitor, is therefore an appealing option for use in neonatal ARV prophylaxis regimens. Limited data exists, however, for raltegravir use in newborns, especially premature neonates. Raltegravir is predominantly eliminated by UGT 1A1 mediated glucuronidation [2] . In term and preterm neonates, UGT activity is decreased at birth but quickly increases during the first few weeks of life [3, 4] and regardless of gestational age at birth [4] . IMPAACT P1097 investigated the washout pharmacokinetics of in utero/intrapartum exposure to raltegravir in neonates born to women living with HIV and reported a median raltegravir elimination half-life of 26.6 (range 9.3-184) h for neonates with a gestational age of at least 37 weeks [5] . The prolonged raltegravir elimination half-life was suspected to reflect low neonatal UGT 1A1 activity and enterohepatic recirculation [5] . In comparison, the geometric mean half-life for raltegravir has been reported in infants aged 4 weeks to less than 6 months as 8.2 (range 2.5-111) h and in infants aged 6 months to less than 2 years as 3.0 (range 1.9-7.4) h [6]. Safe and effective neonatal raltegravir dosing must account for developmental changes in raltegravir elimination over the first few weeks of life [5] . We report a case of therapeutic drug monitoring (TDM) guided raltegravir use for PVT in a premature neonate born to a woman living with perinatally acquired HIV and resistance to various nucleoside reverse transcriptase inhibitors (NRTIs), non-nucleoside reverse transcriptase inhibitors (NNRTIs) and protease inhibitors (PIs).