Resistance testing should be carried out in the mother. Where this is not available, choice of treatment has to be made on the basis of the history of drug exposure and any previous resistance data in the mother. If the infant is found to be infected, then the first HIV-positive sample should also be tested for the resistance pattern of the transmitted virus. The very premature neonate is at risk of necrotizing enterocolitis (NEC) if enteral feeding is commenced too soon or increased too rapidly. It is not known whether very early enteral administration of ART can exacerbate this risk. In a large French case

controlled study of cases of NEC, being an infant of a mother with HIV was associated with an increased risk of NEC (OR 6.63; 95% CI 1.26–34.8; P = 0.025), although the numbers were too small find more to ascertain the effect of maternal and/or infant ART [301]. Premature infants should be commenced on i.v. zidovudine, but once enteral BKM120 molecular weight feeding is established, zidovudine may be given enterally and the premature dosing regimen should be used (Table 1). Enfuvirtide is the only other antiretroviral that is administered parenterally, usually subcutaneously, in adults and children. An unlicensed i.v. dosing regimen has been adapted for use as part of combination ART in neonates at risk of multiresistant HIV (seek expert advice) [300]. 8.1.4 Neonatal PEP should be commenced very soon after birth, certainly

within 4 hours. Grading: 1C There are no clear data on how late infant PEP can be initiated and still have an effect, but all effective Adenosine triphosphate studies of infant PEP have started treatment early and animal data show a clear relationship between time of initiation and effectiveness [302-304]. Immediate administration of PEP is especially important where the mother has not received any antiretroviral therapy. 8.1.5 Neonatal PEP should be given for 4 weeks. Grading: 1C In the original ACTG 076 study, zidovudine was administered for 6 weeks after birth and this subsequently became standard of care [62]. Simplification to zidovudine

twice daily for 4 weeks has become common practice in the UK and data from the NSHPC suggest that regimens adopting this strategy remain highly effective [4]. Recent cohort studies from Ireland [305] and Spain [306] have demonstrated efficacy and reduced haematological side effects with 4 versus 6 weeks of neonatal zidovudine. In a Thai study, where a short course of 3 days of neonatal monotherapy zidovudine PEP was compared to 6 weeks, there was no significantly increased HIV transmission where the mother received zidovudine monotherapy from 28 weeks’ gestation [307]. Whether 4 weeks of zidovudine is necessary for infants born to mothers on cART with fully suppressed HIV is not known, shorter courses may be considered in the future. 8.2.1 PCP prophylaxis, with co-trimoxazole, should be initiated from age 4 weeks in: All HIV-infected infants.