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Pregnant women living with HIV (PWLWH) experience cardiometabolic risk across pregnancy and postpartum, including hypertensive disorders of pregnancy (HDP), gestational diabetes mellitus (GDM), dyslipidemia, obesity, and later metabolic disease. This heterogenous biology reflects gestational adaptation, HIV-associated immune adaptation, antiretroviral therapy (ART), placental function, and underlying cardiometabolic susceptibility. Integrated proteomic-metabolomic prediction studies in PWLWH remain scarce, positioning current evidence as a foundation for biomarker discovery and prospective validation.

This review evaluates molecular and biomarker evidence from PWLWH alongside broader pregnancy literature informing proteomic and metabolomic discovery. Approaches include mass-spectrometry-based proteomics and metabolomics, affinity-based platforms including Olink and SomaScan, nuclear magnetic resonance, targeted assays, and multi-omics integration using regression, network, machine learning, and latent-factor methods. Emphasis is placed on inflammatory, endothelial, angiogenic, lipid, amino-acid, mitochondrial, and immune-metabolic pathways relevant to HDP, GDM, dyslipidemia, and postpartum cardiometabolic risk.

Integrated proteomics and metabolomics offer near-term value for mechanistic discovery and reproducible molecular risk signatures. Translation requires longitudinal cohorts, measured ART exposure, standardized pre-analytics, independent validation, and improvement beyond clinical risk factors. High burden settings additionally require resource-appropriate sampling, simplified targeted assays, local laboratory capacity, sustainable bioinformatics, demonstrable clinical utility, and scalable translational strategies.