When an infant has been started on triple-combination PEP because the maternal VL is >50 HIV RNA copies/mL at 36 weeks and subsequently a delivery maternal VL is <50 HIV RNA copies/mL, then it is reasonable to simplify the infant PEP to monotherapy. Most neonates born in the UK to mothers known to have HIV will be exposed to ART in utero, during delivery and after birth for the first 4 weeks of life. The range of cARTs to which neonates are being exposed in utero continues to increase. Neonatal drug metabolism is generally slower than that of older infants or children and premature neonates have even less efficient metabolism. Owing to a lack of neonatal pharmacokinetic

GW-572016 concentration and efficacy studies and suitable formulations, ART dosing regimens remain restricted to a small proportion of the ARV buy Palbociclib drugs currently manufactured (Table 1). Small pharmacokinetic studies have been performed (zidovudine [24], lamivudine [[25],[26]], tenofovir [11], emtricitabine [27]) and dosing regimens are available for most of the nucleoside analogues and for abacavir from age 1 month [28], while limited study of didanosine in neonates suggests that the pharmacokinetics are highly

variable [9]. The pharmacokinetics of nevirapine in neonates has been described in more detail [[6],[7],[29][[30][#[31]]Ent]267]. Pharmacokinetic-supported dosing is available for the PIs nelfinavir [25] and ritonavir-boosted lopinavir (based on HIV-1 infected infants initiating therapy in

the first 6 weeks of life) [[32][[33][#[34]]Ent]270] and a study that included Montelukast Sodium some infants treated from birth [35]. However, evidence of adrenal suppression has been documented in some neonates treated with lopinavir/ritonavir, particularly when preterm [36], in addition to case reports of cardiac, renal and neurological toxicity, especially in, but not restricted to, premature infants, and including one death during PEP with lopinavir/ritonavir [37]. No effects have been observed with maternal lopinavir/ritonavir in the absence of neonatal dosing. It remains unclear whether these effects are related to lopinavir/ritonavir specifically or could be seen with other ritonavir-boosted PIs. The Writing Group therefore recommends that this PI should be avoided in routine infant PEP and should only be prescribed to preterm neonates in exceptional circumstances. Its use should only be considered after seeking expert advice and where there is multidrug resistance. Close metabolic monitoring in hospital should be undertaken. Nelfinavir, the only other PI with an infant-dosing regimen, will be withdrawn in the near future and will no longer be available for prescription in the UK or elsewhere in Europe. See the CHIVA website for dosing updates (http://www.chiva.org.uk). In contrast to the PIs, nevirapine efficiently crosses the placenta (see below) and is well absorbed by the neonate [38].