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A Study to Evaluate the Effects of Genetic Factors on the Pharmacokinetics of Antiretroviral Drugs During Pregnancy and Lactation

NCT02269462 · Status: COMPLETED · Type: OBSERVATIONAL · Enrollment: 460

Last updated 2017-09-06

No results posted yet for this study

Summary

Mother-to-child transmission of HIV (MTCT) during pregnancy and breastfeeding is prevented with maternal antiretroviral drugs (ARV) and infant nevirapine post-exposure prophylaxis (PEP). However, the pharmacokinetics of certain ARVs is associated with marked inter-individual variability. This variability has been associated with single nucleotide polymorphisms (SNPs) in genes encoding metabolising enzymes, transporters and transcriptional regulators. Pregnancy is also associated with additional changes in pharmacokinetics. The resulting sub-therapeutic or supra-therapeutic drug exposures may have serious consequences for virological control, MTCT, emergence of drug resistance, and toxicity. Foetal and infant exposure to maternal ARV during pregnancy and breastfeeding is believed to play a role in the prevention of mother-to-child transmission of HIV (PMTCT). However, such exposures may also result in toxicity. For example, efavirenz is contraindicated in children less than 3 years old or 10kg but transferred to breastfed babies through breast milk. On the other hand, double exposure to nevirapine from breast milk and PEP may also predispose breastfed infants to nevirapine-associated toxicity.

In the proposed study, the influence of selected SNPs in certain drug disposition genes on the pharmacokinetics of efavirenz and nevirapine during pregnancy and lactation, as well as the level of infant exposure to both drugs through breast milk, will be studied. Mathematical models will be developed to predict potential dose optimisation strategies during pregnancy, and to predict infant exposure to maternal drugs through breast milk.

Conditions

  • HIV
  • Pregnancy
  • Breastfeeding

Interventions

DRUG

Efavirenz

600 mg once daily in combination with other drugs (e.g. tenofovir and emtricitabine)

DRUG

Nevirapine

200 mg twice daily in combination with other drugs (e.g. tenofovir and emtricitabine)

Sponsors & Collaborators

  • University of Liverpool

    collaborator OTHER

  • Obafemi Awolowo University Teaching Hospital

    collaborator OTHER

  • Adeniyi Olagunju

    lead OTHER

Principal Investigators

  • Adeniyi Olagunju · Obafemi Awolowo University, Nigeria

  • Andrew Owen, PhD · University of Liverpool, United Kingdom

Eligibility

Min Age
18 Years
Sex
FEMALE
Healthy Volunteers
No

Timeline & Regulatory

Start
2012-12-31
Primary Completion
2013-10-31
Completion
2013-11-30

Countries

  • Nigeria

Study Locations

More Related Trials

Entities

Diseases

Read the full study record

This page highlights key information. For complete eligibility criteria, study locations, investigator contacts, and the full protocol, visit the original record on ClinicalTrials.gov.

View NCT02269462 on ClinicalTrials.gov