Abstract Body

Background: MTCT of HIV can occur at different time periods perinatally: in utero, at time of delivery or during breast feeding. Breast feeding accounts for 6.5%- 25.9% of infections worldwide, with the majority of transmissions occurring in the first 6 weeks of life. ARVs with good penetration into breast milk (BM) have the greatest impact on decreasing MTCT transmission through breastfeeding. Methodology: Nine HIV+ postpartum women on stable HAART with an undetectable viral load added Etravirine (ETR) to their current regimen on postpartum Day 1 and continued for 14 days. Intensive PK sampling of BM and plasma was done on postpartum days 5 (D5) and 14 (D14) at times 0, 2, 5, 8 and 24 hours after the dose of ETR. BM and plasma HIV-1 RNA viral load (VL) were quantified. ETR drug concentrations were measured by a validated LC/MS/MS assay. Non-compartmental analysis was used to estimate PK parameters. Results: The median BM concentration of ETR on D5 was 241.46 ng/ml (160.76-890.8) and on D14 was 797.7 ng/ml (161.02-2714.2) p=0.046. The median plasma concentrations were 299.9 ng/ml (52.76-563.8) and 196.9 ng/ml (131.88-706.4) on D5 and D14 respectively. The median BM:plasma ratio were 1.09 ng/ml (0.59-3.04) on D5 and 3.27 ng/ml on D14 (1.25-4.55) P=0.01. BM concentrations exceeded the upper limit of the ETR IC 50 range (0.39-2.4 ng/ml) in all patients. HIV RNA levels were detectable in the BM of two patients despite undetectable plasma HIV RNA. ETR AUC 0-24 and BM:plasma ratios did not differ in the detectable vs. the undetectable women. Conclusions: ETR penetration into BM is largely driven by plasma PK and exceeds the plasma HIV inhibitory concentration at all time points. This study suggests that unbound ETR readily diffuses from blood to the breast compartment likely because of its lipophilicity. However, differences in concomitant ARVs and individual pharmcodynamics may allow for compartmental viral replication. HAART combinations that include ETR may prove useful for prevention of BM MTCT in resource limited countries where exclusive breastfeeding is recommended.