Kinetics of nevirapine and its impact on HIV-1 RNA levels in maternal plasma and breast milk over time after perinatal single-dose nevirapine
Journal of Acquired Immune Deficiency Syndromes
Makerere University-Johns Hopkins University (MU-JHU) Research Collaboration, MU-JHU Research Building, Old Mulago Hill Road, Kampala, Uganda; Centers for Disease Control and Prevention, Atlanta, GA, United States; Departments of Medicine (Clinical Pharmacology), United States; Departments of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD, United States; Department of Strategic Information, Cape Town, South Africa; Mucosal and Vaccine Research Program Colorado (MAVRC), Division of Infectious Diseases, University of Colorado, Denver, CO, United States
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. © 2012 by Lippincott Williams & Wilkins.
nevirapine; virus RNA; adult; article; breast milk; controlled study; female; human; Human immunodeficiency virus 1; Human immunodeficiency virus infected patient; Human immunodeficiency virus infection; infant; major clinical study; maternal plasma; perinatal drug exposure; pregnant woman; priority journal; single drug dose; tandem mass spectrometry; virus load; Adult; Anti-HIV Agents; Female; HIV Infections; HIV-1; Humans; Infant; Infant, Newborn; Infectious Disease Transmission, Vertical; Male; Milk, Human; Nevirapine; Plasma; Pregnancy; RNA, Viral; Tandem Mass Spectrometry; Time Factors; Uganda; Viral Load; Young Adult