8.1.3. Three-drug infant

therapy is recommended for all circumstances other than Recommendation 8.1.1 where maternal viral load at 36 weeks’ gestation/delivery is not < 50 HIV RNA copies/mL. Grading: 2C Delivery with a detectable maternal viral load (> 50 HIV RNA copies/mL) is not uncommon. The virus may never have been suppressed due to: premature delivery; poor adherence; very high starting maternal viral load (> 100 000 HIV RNA copies/mL); or late commencement of cART. Or there may have been viral rebound during gestation due to poor adherence or development of resistance. There are no randomized trials of combination-therapy PEP for infants where mothers RG-7388 mw are receiving cART. In a French study, transmission rates with dual therapy (zidovudine and lamivudine) to both the neonate and mother (1.6%) were lower than zidovudine monotherapy reported in historical controls (6.8%; OR 0.22; 95% CI 0.2–0.5) [283]. The strength of recommendation is proportionate to the estimated risk of transmission. Thus, benefit of additional neonatal VX-770 concentration therapy is anticipated at higher viral loads, in circumstances where resistance is suspected or confirmed and where viral load is increasing despite treatment. As with the recommendations regarding PLCS at viral loads < 400 HIV RNA copies/mL, favourable trends can be

considered in the risk assessment. Despite the lack of evidence for its use, NSHPC data indicate a trend towards increasing use of triple-neonatal PEP. When an infant has been started on triple-combination PEP because the maternal viral load is > 50 HIV RNA copies/mL at 36 weeks and subsequently a delivery maternal viral load 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 combinations of ART 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. Due to a lack of neonatal pharmacokinetic Sodium butyrate and efficacy studies and suitable formulations, ART dosing regimens remain restricted to a small proportion of the antiretroviral drugs currently manufactured (Table 1). Small pharmacokinetic studies have been performed (zidovudine [284], lamivudine [285, 286], tenofovir [160], emtricitabine [287]) and dosing regimens are available for most of the nucleoside analogues and for abacavir from age 1 month [288], while limited study of didanosine in neonates suggests that the pharmacokinetics are highly variable [111]. The pharmacokinetics of nevirapine in neonates has been described in more detail [73, 75, 289-291].