Kinetics of nevirapine and its impact on HIV-1 RNA levels in maternal plasma and breast milk over time after perinatal single-dose nevirapine.
OBJECTIVE
To determine kinetics after single-dose nevirapine and the impact on HIV RNA [viral load (VL)] in maternal plasma and breast milk (BM).


METHODS
Cohort of 120 HIV-1-infected pregnant Ugandan women received perinatal single-dose nevirapine alone and followed up with their infants through 24 weeks postdelivery. We assessed the relationship of nevirapine concentration (tandem mass spectroscopy) and HIV-1 VL (Roche AMPLICOR HIV-1 Kit, version 1.5) in maternal plasma and BM over time.


RESULTS
At week 1 postpartum, NVP (≥10 ng/mL) was detected in all 53 plasma and 47 of 51 (92.2%) BM samples with median (interquartile ranges) of, respectively, 171 (78-214) ng/mL and 112 (64-158) ng/mL, P = 0.075, which decreased subsequently with traces persisting through week 4 in plasma. Plasma and BM VL dropped by week 1 and were highly correlated at delivery (R = 0.71, P < 0.001) and week 1 (R = 0.69, P < 0.001) but not thereafter. At week 1, VL correlated inversely with NVP concentration in plasma (R = 0.39, P = 0.004) and BM (R = 0.48, P = 0.013). There was a VL rebound in both compartments, which peaked at week 4 to levels greater than those at week 1 [significantly in plasma (P < 0.001) but not in BM] and remained stable thereafter. Median VL was consistently greater (11- to 50-fold) in plasma than BM at all time points (all P < 0.001).


CONCLUSIONS
After single-dose nevirapine, NVP concentration was comparably high through week 1, accompanied by suppression of plasma and BM VL. A longer "tail" (>1 week) of potent postnatal antiretroviral drugs is warranted to minimize the observed VL rebound and potential for NVP resistance as a result of persistent NVP traces.
Makerere University-Johns Hopkins University Research Collaboration, Kampala, Uganda. jaizire@mujhu.org
Jim
J
Aizire
Michelle S
MS
McConnell
Peter
P
Mudiope
Michael
M
Mubiru
Flavia
F
Matovu
Teresa L
TL
Parsons
Ali
A
Elbireer
Monica
M
Nolan
Edward N
EN
Janoff
Mary Glenn
MG
Fowler
D000328:Adult; D019380:Anti-HIV Agents / Q000008:administration & dosage / Q000493:pharmacokinetics*; D005260:Female; D015658:HIV Infections / Q000188:drug therapy / Q000517:prevention & control* / Q000821:virology; D015497:HIV-1 / Q000302:isolation & purification*; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D018445:Infectious Disease Transmission, Vertical / Q000517:prevention & control; D008297:Male; D008895:Milk, Human / Q000737:chemistry*; D019829:Nevirapine / Q000008:administration & dosage / Q000493:pharmacokinetics*; D010949:Plasma / Q000737:chemistry*; D011247:Pregnancy; D012367:RNA, Viral / Q000097:blood; D053719:Tandem Mass Spectrometry; D013997:Time Factors; D014454:Uganda; D019562:Viral Load; D055815:Young Adult
D019380:Anti-HIV Agents; D012367:RNA, Viral; D019829:Nevirapine