Background:  The kinetics of nevirapine (NVP) levels in maternal plasma and breast milk may mediate the duration of protection against peri- and post-natal HIV infection.

Methods:  We prospectively assessed NVP levels in maternal blood and breast milk at delivery and 1, 2, and 4 weeks by high-pressure liquid chromatographic/mass spectroscopy after perinatal mother/infant single-dose NVP (sdNVP) and its impact on HIV RNA among HIV-1 transmitting and non-transmitting mother-infant pairs. Eligible HIV-1-infected pregnant women attending Mulago National Referral Hospital in Kampala, Uganda, were enrolled during their third trimester from October 2003 to April 2004, and followed to 24 weeks postpartum. All mother-infant pairs received standard of care perinatal HIVNET 012 SD NVP alone. Quantitative viral load HIV-1 RNA polymerase chain reaction was performed on maternal plasma and breast milk supernatant collected at delivery and 1, 4, 10, and 24 weeks. 

Results:  Of the 120 enrolled mothers 108 (90%) had completed data through week 24, among whom 17 (15.7%) showed mother-to-child transmission (MTCT) of HIV-1 by week 24. The baseline median (IQR) for age was 25 (23 to 28) years, CD4 cell count was 422 (270 to 618) cells/mL, and viral load was 27,700 (6652 to 70,333) copies/mL. At week 1, the NVP concentration (median [IQR]) in plasma was 157 (91 to 179) ng/mL among transmitters and 180 (73 to 235) ng/mL among non-transmitters, P = 0.253; and in breast milk 112 (104 to 134) ng/mL among transmitters and 119 (62 to 159) ng/mL among non-transmitters, P = 0.591. The declining NVP concentration time profiles at 2 and 4 weeks were similar in both plasma and breast milk with slightly lower levels in breast milk. There was a drop in HIV RNA levels in both plasma and breast milk within the first week which returned to baseline levels thereafter. The figure below illustrates maternal plasma and breast milk viral load from birth through 24 weeks postpartum comparing transmitters to non-transmitters. 

Conclusions:  Plasma and breast milk NVP persisted beyond 2 weeks postpartum, with median NVP levels >10 ng/mL (IC₅₀ for NVP) present at week 2. However, declines in plasma and breast milk viral load reversed after week 2. Given the slow decay of NVP levels persisting till week 4, consideration should be given to extending the 1 week “tail” of concomitant antiretroviral drugs used to minimize NVP-resistance induction.