Persistence of nevirapine in breast milk and plasma of mothers and their children after single-dose administration

• Published in: Journal of antimicrobial chemotherapy 2009-01, Vol.63 (1), p.170-177
• Main Authors: Kunz, Andrea, Frank, Monika, Mugenyi, Kizito, Kabasinguzi, Rose, Weidenhammer, Astrid, Kurowski, Michael, Kloft, Charlotte, Harms, Gundel
• Format: Article
• Language: English
• Subjects: Adult; Antibiotics. Antiinfectious agents. Antiparasitic agents; Biological and medical sciences; breastfeeding; Breastfeeding & lactation; Chromatography, Liquid; Disease transmission; Drug resistance; Female; HIV; HIV Infections - prevention & control; Human immunodeficiency virus; Human viral diseases; Humans; Immunodeficiencies; Immunodeficiencies. Immunoglobulinopathies; Immunopathology; Infant, Newborn; Infectious Disease Transmission, Vertical - prevention & control; Infectious diseases; Male; Medical sciences; Milk, Human - chemistry; Mothers; Mutation; Nevirapine - administration & dosage; Nevirapine - pharmacokinetics; Pharmacology. Drug treatments; Plasma - chemistry; population pharmacokinetics; Pregnant Women; Tandem Mass Spectrometry; Uganda; Viral diseases; Viral diseases of the lymphoid tissue and the blood. Aids
• ISSN: 0305-7453; 1460-2091
• DOI: 10.1093/jac/dkn441

Objectives Nevirapine is widely used in the developing world for the prevention of mother-to-child transmission (PMTCT) of HIV. A single mutation in the HIV genome is sufficient to lead to significant nevirapine resistance. Persistence of low-level drug concentrations in body compartments can foster resistance formation. In this study, concentration–time courses of nevirapine after single-dose administration were analysed over an extended post-partum period. Patients and methods Breast milk and plasma samples of 62 HIV-positive Ugandan mother–child pairs who had received single-dose nevirapine were collected at delivery and 1, 2 and 6 weeks post-partum. Nevirapine concentrations were quantified by LC/tandem-mass-spectrometry using a quantification limit of 15 ng/mL, and a population pharmacokinetic (PK) analysis was performed. Results Concentration–time profiles in breast milk, maternal plasma and child plasma showed similar shapes. At week 1, median nevirapine concentrations were 164 ng/mL in maternal plasma, 114 ng/mL in breast milk and 183 ng/mL in child plasma. The population PK model predicted nevirapine concentrations >10 ng/mL (IC50 for nevirapine) for 13 days in breast milk, 14 days in maternal plasma and 18 days in child plasma in 80% of the samples. Conclusions Nevirapine concentrations were present for 2–3 weeks in the three compartments. The concentrations are probably sufficiently high to protect most breastfed children from HIV transmission during the first 2 weeks. The long presence of slowly decreasing levels of nevirapine is likely to induce resistance formation. Post-natal addition of antiretrovirals for 1 week only, as recommended in the current PMTCT guidelines, will not suffice to avoid nevirapine resistance formation.