Relationship between raltegravir trough plasma concentration and virologic response and the impact of therapeutic drug monitoring during pregnancy

Background Limited data is available on raltegravir (RAL) pharmacokinetics during pregnancy and the value of therapeutic drug monitoring (TDM) in pregnancy is unknown. This study aims to describe RAL trough plasma concentrations (C-trough) during pregnancy and review the impact of RAL TDM on outcomes. Methods Women from the prospective mother-infant HIV cohort of Mother and Children's Infectious Diseases Center who received RAL during their pregnancy between 2011-2020 were included. TDM reports were reviewed and C-trough values estimated when possible, using historical RAL half-lives. Results We included 76 pregnant women of which 47 underwent TDM. We observed a significant association between virological response and C-trough (p-value .034) with an increase of 0.1 mg/L corresponding to a 2.96 reduction in the risk of having a detectable viral load. The results indicated that in pregnant women a RAL C-trough threshold of 0.04 mg/L has a higher specificity (75%) as compared to our current C-trough target value of 0.02 mg/L (25%) and an acceptable sensitivity (77%). No significant differences were observed between C-trough at each trimester. When comparing pregnancies with and without TDM, no statistically significant differences were observed in the virologic response during pregnancy and at delivery, or with the need for triple antiretroviral prophylaxis in newborns. Conclusions An association between RAL C-trough and viral load was observed and achieving a RAL C-trough of 0.04 mg/L or greater is a predictor of virologic response in pregnant women. The impact of TDM in pregnancy, however, could not be demonstrated.