Mother Matters

<jats:p>This thesis examines the pharmacokinetics, safety, and implementation of antiretroviral therapy during pregnancy and lactation in women living with HIV. Since pregnant and breastfeeding women are often excluded from clinical research, important knowledge gaps remain regarding drug exposure, efficacy, and safety for both mother and child. The pharmacokinetics of bictegravir change during pregnancy, yet remains efficacious. Exposure to long-acting injectable cabotegravir during pregnancy was comparable to that observed in non-pregnant individuals, whereas rilpivirine concentration were decreased. To assess exposure through breastmilk, a bioanalytical assay was developed and validated. This assay was applied in studies involving healthy lactating volunteers and women living with HIV, supplemented by PBPK modelling to predict concentrations in breastmilk. The observed and predicted concentrations were generally low and suggest no clinically relevant toxicity to infants. In addition, factors influencing the implementation of guideline changes regarding counseling on infant feeding options were explored. Finally, the thesis advocates for more equitable research and care through innovative study designs and the early, responsible inclusion of pregnant and breastfeeding women in clinical research.</jats:p>