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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
medicine
Clinical and genetic determinants of plasma nevirapine exposure following an intrapartum dose to prevent mother-to-child HIV transmission
Journal of Infectious Diseases, Volume 208, No. 4, Year 2013
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Description
Objective. Nevirapine is metabolized by cytochrome P450 (CYP) 2B6 and CYP3A4. We characterized relationships between clinical parameters, human genetics, pharmacokinetics, and human immunodeficiency virus type 1 (HIV-1) drug resistance mutations in pregnant women following single-dose intrapartum nevirapine. Methods. In AIDS Clinical Trials Group study A5207, women received nevirapine at onset of labor and were randomly assigned to receive lamivudine/zidovudine, emtricitabine/tenofovir, or lopinavir/ritonavir for 7 or 21 days. Plasma nevirapine level was quantified on postpartum day 1 and on weeks 1, 3, and 5. We assayed 214 polymorphisms in CYP2B6 and other genes and evaluated associations with pharmacokinetic parameters, including elimination constant, time to protein-adjusted 50% inhibitory concentration (IC 50), and week 5 nevirapine level below the quantification limit. Results. Among 301 women with evaluable pharmacokinetic and genotype data, lower body mass index and random assignment to receive lopinavir/ritonavir were associated with more rapid nevirapine elimination. Among those of African ancestry, longer time to IC50 was associated with CYP2B6 983T→C (P =. 004) but not with CYP2B6 516G→T (P =. 8). Among Indians, slower nevirapine elimination was associated with CYP2B6 516G→T (P =. 04). Emergent resistance was infrequent and not associated with pharmacokinetics or CYP2B6 genotype. Conclusions. The effects on plasma drug exposure following single-dose nevirapine may be greater for CYP2B6 983T→C than for 516G→T and are less pronounced than at steady state. © The Author 2013.
Available Materials
https://efashare.b-cdn.net/share/pmc/articles/PMC3719905/bin/supp_208_4_662__index.html
https://efashare.b-cdn.net/share/pmc/articles/PMC3719905/bin/supp_jit223_jit223supp_table1.docx
https://efashare.b-cdn.net/share/pmc/articles/PMC3719905/bin/supp_jit223_jit223supp_table2.docx
Authors & Co-Authors
Vardhanabhuti, Saran
United States, Boston
Harvard T.h. Chan School of Public Health
Acosta, Edward P.
United States, Birmingham
The University of Alabama at Birmingham
Ribaudo, Heather J.
United States, Boston
Harvard T.h. Chan School of Public Health
Sévère, Patrice D.
Haiti, Port-au-prince
Groupe D’étude Haïtien Sur le Sarcome de Kaposi et Les Infections Opportunistes
Lalloo, Umesh Gangaram
South Africa, Durban
The Nelson R. Mandela Medical School
Kumarasamy, Nagalingeswaran
India, Chennai
Vhs Medical Centre India
Taulo, Frank O.
United States, Baltimore
Johns Hopkins University
Kabanda, J.
Uganda, Kampala
Joint Clinical Research Center Uganda
Oneko, Olola Achieng
Tanzania, Moshi
Kilimanjaro Christian Medical Centre
Ive, Prudence D.
South Africa, Johannesburg
University of the Witwatersrand
Sambarey, Pradeep
India, Pune
B.j. Medical College, Pune
Chan, Ellen S.
United States, Boston
Harvard T.h. Chan School of Public Health
Hitti, Jane E.
United States, Seattle
University of Washington
Hong, Francis
United States, Pittsburgh
University of Pittsburgh
McMahon, Deborah K.
United States, Pittsburgh
University of Pittsburgh
Haas, David William
United States, Nashville
Vanderbilt University School of Medicine
United States, Nashville
Immunology
Statistics
Citations: 23
Authors: 16
Affiliations: 14
Identifiers
Doi:
10.1093/infdis/jit223
ISSN:
00221899
Research Areas
Genetics And Genomics
Infectious Diseases
Maternal And Child Health
Participants Gender
Female