Background:  We wanted to correlate nevirapine (NVP) presence and level in cord bloods of infants born to HIV-1-infected women with self-report of timing of dose and HIV-1 transmission at 6 weeks of age.

Methods:  All available cord blood samples from the infants of mothers enrolled in the HIV NET 012 trial who were randomly assigned to receive either NVP or zidovudine (AZT) at the onset of labor were tested for NVP concentration using a validated high performance liquid chromatography assay which has a limit of sensitivity of 25 ng/mL (range 25 to 10,000 ng/mL).

Results:  NVP was detected in the cord blood of 244 of the 259 of the infants (94%) whose mother reported that she took a 200-mg tablet of NVP in labor > 1 hour before delivery and in 12 of 13 of the infants (92%) whose mother reported that she took NVP < 1 hour before delivery. The median NVP cord blood concentration was 1238 ng/mL (interquartile range 905 to 1474 ng/mL) and 122 ng/mL (64 to 321 ng/mL) for women who reported taking NVP > 1 hour or < 1 hour before delivery, respectively (p < 0.001). The median NVP cord blood concentration of infants who were HIV-1^– at birth, but HIV-1⁺ at 6 to 8 weeks of age (n = 11) was 916 ng/mL (737 to 1245 ng/mL) and was not significantly different than the median concentration of 1192 ng/mL (875 to 1471 ng/mL) for uninfected infants (n = 236) (p = 0.203). NVP was detected in the cord blood of 1 of the 278 infants tested for NVP whose mothers were assigned to receive AZT.

Conclusions:  Cord blood NVP concentration correlated well with self-report of NVP administration and timing of dose before delivery.  While NVP cord blood concentration did not correlate with HIV-1 transmission, the number of infants infected between birth and 6 to 8 weeks of age was small (n = 11), limiting statistical power. Additionally, cord blood drug levels reflect only pre-exposure infant prophylaxis, and not the infant post-exposure dose component. The high adherence rate in the HIV NET 012 study supports the simplicity and deliverability of this regimen which allows HIV-infected pregnant women in resource-limited settings to self-administer the NVP tablet at labor onset. The lower efficacy rates of the single-dose NVP regimen reported in some field programs may reflect poorer patient instruction/adherence than seen in HIV NET 012.

Keywords: nevirapine; cord blood; transmission