Aging, HIV Status, and Sex Differentially Influence Antiretroviral Therapy Disposition Pathways in Rectosigmoid Tissue and Peripheral Blood Mononuclear Cells

Aging (65–80) versus young (18–50) HIV-seronegative adults shows broader remodeling of ARV disposition-related proteins in rectosigmoid colon tissue, including drug transport and nucleotide homeostasis pathways.

• Why it matters: Age-related changes may alter ARV pharmacology, but the molecular mechanisms in HIV-relevant tissue compartments like rectosigmoid colon remain unclear, especially across sex and HIV status.
• What they did: Using LC-MS proteomics, the study compared rectosigmoid tissue and PBMC from young HIV-seronegative adults, older HIV-seronegative adults, and older virally suppressed people living with HIV, then ran pathway analyses focused on ARV disposition.
• The result: HIV-associated proteome effects were more prominent in PBMC, while aging drove extensive rectosigmoid changes; sex further modulated some age-linked proteins, providing a mechanistic basis for future ART and HIV pre-exposure prophylaxis studies in older adults.

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