In ACTG 076 neonatal zidovudine 2 mg/kg every 4 h (five doses) was given for 6 weeks. Monotherapy for the infant is appropriate when there is a very low risk of Ixazomib HIV transmission. This occurs when a mother on combination therapy delivers with a VL <50 HIV RNA copies/mL. The neonate should receive single-drug

therapy for 4 weeks; this is practically easier for the family and reduces the risk of adverse events. With many years of experience, twice-daily zidovudine monotherapy is the neonatal treatment of choice, whatever the maternal ART combination. For infants born to mothers on fully suppressive ART, zidovudine monotherapy PEP remains reasonable even where the mother has a previous history of zidovudine exposure with resistance (thymidine-associated mutations). On HAART, the risk of transmission

in the mother with fully suppressed viral replication is extremely low ( about 0.1%), and although history of zidovudine resistance in maternal virus and infant PEP regimen has not been dissected, the frequency of transmission of zidovudine-resistant virus is concomitantly very low. Data from the era when only maternal zidovudine monotherapy was available indicate preferential transmission of wild-type over zidovudine-resistant virus when a mixed population of virions are present [12]. In the Swiss cohort, none of six infants born to mothers harbouring zidovudine-resistant HIV (based on codon 215 analysis however only) became infected [13]. In a subset of participants Erastin datasheet of the ACTG 076 study, the prevalence of low-level zidovudine

resistance was 4.3% (mutation at codon 70) and no significant increase in the risk of transmission was observed after adjusting for VL at delivery (OR 4.8; with wide 95% CI 0.2–131; P = 0.35) [14]. High-level resistance was not reported and the median CD4 cell count in the women was 540 cells/μL. In retrospective cohort studies from France [15] and the USA [16], 20% and 8.3%, respectively, of HIV-positive newborns had zidovudine-resistance mutations after maternal zidovudine prophylaxis. In the WITS, lower CD4 cell count and higher HIV VL at delivery were associated with increased risk of transmission while in the multivariate analysis, the presence of at least one mutation associated with zidovudine resistance was also associated with an increased risk of transmission (OR 5.15; 95% CI 1.4–18.97) [17]. With infant feeding patterns, it is difficult to separate drug dosing from feeds, so drugs without food restrictions are preferred, an advantage of zidovudine. Important in this age group, where therapeutic options are more limited than in older children and adults, should transmission occur multidrug resistance is avoided. However, some clinicians prefer to choose another ARV, with no history of maternal resistance, for infant post-exposure monotherapy.