Understanding the Pharmacokinetics of Antiretroviral Drugs in Breastfeeding Mother-Infant Pairs. (360G-Wellcome-104422_Z_14_Z)

Despite evidence that perinatal use of antiretroviral therapy (ART) can reduce the rates of mother to child transmission (MTCT) of HIV to less than 1%, approximately 430 000 children are infected annually. Consequently, WHO recommends commencing pregnant HIV+ women on lifelong ART irrespective of CD4 count or clinical stage. Whilst benefits are likely, this strategy carries several potential risks; increasingly, infants will be exposed to ART in utero and through breastmilk (BM). Several recent studies highlight both toxicities and the risk of multi-class drug resistance should the PMTCT fail. My aim is to characterise ARV accumulation in BM, relative infant dosing and systemic absorption following feeding. Sparse pharmacokinetic sampling from postpartum women receiving ARVs in Kampala will evaluate covariates (eg gestational age, birth weight, nutritional status, pharmacogenetics, maternal CD4) of infant ARV exposure. Clinical outcome measures will include HIV viral load in mothe r, BM and infant, drug safety, and vertical transmission. A population pharmacokinetic (and pharmacodynamic) model will characterise ARV exposure and efficacy in mother-infant pairs, and simulate outcomes with alternative dosing regimens and combinations. I have developed novel dried blood and dried BM spot methodology for some first line ARVs in support of this Fellowship.