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

• Status: Completed
• Trial end date: 2013-11-01
• Target enrollment: 0
• Participant gender: Female

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.

• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Adeniyi Olagunju
• Collaborators: Obafemi Awolowo University Teaching Hospital; University of Liverpool
• Treatments: Efavirenz; Nevirapine

Criteria

Inclusion Criteria:

• HIV positive

• breastfeeding

• enrolled in PMTCT programme

• started efavirenz- or nevirapine-containing regimen during pregnancy

Exclusion Criteria:

• exclusive replacement feeding

• mixed feeding before 6 months

• severe maternal or infant illness

• maternal or infant treatment with other drugs or herbal medication with known or uncertain interaction with study drug