Chantarangsu S., Cressey Tim, Mahasirimongkol S., Capparelli E., Tawon Y., Ngo Giang Huong Nicole, Jourdain Gonzague, Lallemant Marc, Chantratita W. (2009). Influence of CYP2B6 polymorphisms on the persistence of plasma nevirapine concentrations following a single intra-partum dose for the prevention of mother to child transmission in HIV-infected Thai women. Journal of Antimicrobial Chemotherapy, 64 (6), p. 1265-1273. ISSN 0305-7453.
Titre du document
Influence of CYP2B6 polymorphisms on the persistence of plasma nevirapine concentrations following a single intra-partum dose for the prevention of mother to child transmission in HIV-infected Thai women
Chantarangsu S., Cressey Tim, Mahasirimongkol S., Capparelli E., Tawon Y., Ngo Giang Huong Nicole, Jourdain Gonzague, Lallemant Marc, Chantratita W.
Source
Journal of Antimicrobial Chemotherapy, 2009,
64 (6), p. 1265-1273 ISSN 0305-7453
To investigate the association of single nucleotide polymorphisms (SNPs) with nevirapine concentrations following intra-partum single-dose nevirapine. Plasma and DNA samples were obtained from 330 HIV-infected Thai women who received intra-partum single-dose nevirapine in the PHPT-2 clinical trial to prevent perinatal HIV transmission. Nine SNPs within CYP2B6, CYP3A4 and ABCB1 were genotyped by real-time PCR. Nevirapine plasma concentrations were determined by HPLC and used in a population pharmacokinetic analysis. Higher nevirapine exposure was observed in women carrying the CYP2B6 516G > T polymorphism, but this did not reach statistical significance (P = 0.054). The TGATC CYP2B6 haplotype (g.3003T, 516G, 785A, g.18492T and g.21563C) was associated with increased nevirapine clearance and lower exposure (P = 0.0029). The median time for nevirapine concentrations to reach 10 ng/mL post-partum (nevirapine IC50 for HIV-1) was 14 days [interquartile range (IQR, 14-18)] for TGATC homozygotes, 16 days (14-20) for TGATC heterozygotes and 18 days (14-20) for non-TGATC homozygotes (P = 0.020). The CYP2B6 516G > T impact on nevirapine concentrations was less pronounced after intra-partum single-dose nevirapine than reported under steady-state conditions, perhaps due to lack of enzyme auto-induction at the time of dosing. Although the TGATC CYP2B6 haplotype may shorten the persistence of nevirapine post-partum, its practical implications for the prevention of HIV transmission or selection of resistance mutations are likely limited.
