Integrating Omics to Advance Antiretroviral Pharmacology in Pregnancy: Dolutegravir‐Based Regimens as a Case Study

Abstract

Dolutegravir is central to antiretroviral therapy in pregnancy, although conventional pharmacokinetic measures cannot fully explain variability in maternal cardiometabolic outcomes or fetal exposure. This narrative review proposes an integrated omics framework linking pharmacogenomics, transcriptomics, proteomics, and metabolomics with longitudinal pharmacokinetics and clinical phenotyping. Using dolutegravir as a case study, we examine genetic determinants of drug disposition, gestational changes in molecular pathways, and emerging evidence implicating adipose dysfunction, mitochondrial metabolism, lipid remodeling, and insulin resistance. We distinguish established pharmacokinetic findings from mechanistic hypotheses requiring pregnancy‐specific validation. Proposed studies combine serial maternal sampling, targeted placental and adipose investigations, and offspring follow‐up, while accounting for HIV, antiretroviral backbone, gestational physiology, and environmental confounding. Prespecified analyses, analytical validation, and independent replication are essential to avoid overinterpretation. Integrated omics should complement, not replace, pharmacometrics, ultimately identifying reproducible mechanisms and clinically useful biomarkers to inform individualized monitoring and treatment strategies while preserving dolutegravir's proven virologic benefits.