Suboptimal nevirapine steady-state pharmacokinetics during intrapartum compared with postpartum in HIV-1-seropositive Ugandan women

Mohammed Lamorde, Pauline Byakika-Kibwika, Violet Okaba-Kayom, John P. Flaherty, Marta Boffito, Rhoda Namakula, Mairin Ryan, Clemensia Nakabiito, David J. Back, Saye Khoo, Concepta Merry, Kimberly K. Scarsi

Research output: Contribution to journalArticlepeer-review

21 Scopus citations

Abstract

Background: Conflicting data exist regarding the effect of pregnancy on steady-state nevirapine pharmacokinetics (PK), although steady-state nevirapine concentrations during pregnancy have never been characterized in sub-Saharan Africa. Methods: This was a longitudinal intensive PK study in Ugandan pregnant women receiving nevirapine-based antiretroviral therapy. Participants underwent intensive 12-hour PK sampling during the second trimester (T2; n = 4), third trimester (T3; n = 15) and 6 weeks postpartum (PP; n = 15). HIV-1 RNA was performed within 2 weeks of each visit. Nevirapine C12 above 3000 ng/mL was classified as optimal based on the suggested value for therapeutic drug monitoring. Results: The pharmacokinetics of nevirapine were influenced by pregnancy, demonstrated by a 20% reduction in the maximum concentration, minimum concentration (C12), and area under the curve between T3 and PP visits (P = 0.001, P = 0.011 and P = 0.005, respectively). Ten subjects (66.7%) had C12 values <3000 ng/mL during T3. Of these participants, 7 partcipant's C12 concentrations increased to >3000 ng/mL during the PP visit. HIV-1 RNA were <1000 copies per milliliter at T3 and <400 copies per milliliter at PP in all patients. Conclusions: Nevirapine exposure was reduced in Ugandan women during their third trimester compared with the same women PP, however, HIV RNA remained <1000 copies per milliliter. The long-term impact of intermittent suboptimal nevirapine concentrations during pregnancy is unknown.

Original languageEnglish (US)
Pages (from-to)345-350
Number of pages6
JournalJournal of Acquired Immune Deficiency Syndromes
Volume55
Issue number3
DOIs
StatePublished - Nov 1 2010

Keywords

  • HIV
  • Sub-Saharan Africa
  • antiretroviral agents
  • pharmacokinetics
  • pregnancy

ASJC Scopus subject areas

  • Infectious Diseases
  • Pharmacology (medical)

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