# Cytomegalovirus in HIV: A Modifiable Driver of Inflammation, Frailty, and Aging

## TL;DR

This paper reviews how cytomegalovirus (CMV) contributes to aging and health issues in people with HIV, and explores potential treatments to mitigate these effects.

## Contribution

The paper highlights CMV as a modifiable driver of aging in HIV patients and evaluates emerging interventions like antiviral drugs and vaccines.

## Key findings

- CMV drives immune senescence and chronic inflammation in HIV patients despite antiretroviral therapy.
- Letermovir and vaccines show promise in reducing CMV-related inflammation and improving health outcomes.
- CMV is linked to multiple aging-related conditions including cardiovascular disease, diabetes, and cancer.

## Abstract

Cytomegalovirus (CMV) infection is nearly universal among people with HIV (PWH) and contributes to chronic inflammation, immune senescence, and accelerated biological aging despite suppressive antiretroviral therapy (ART). This review summarizes recent advances in understanding the role of CMV in multimorbidity and aging in PWH, focusing on immune and tissue-based mechanisms, comorbidities, and emerging interventions.

CMV reactivation drives clonal T-cell expansion, innate immune reprogramming, adipose tissue inflammation, metabolic rewiring, and durable cellular epigenetic changes that amplify risks for vascular disease, frailty, brain health disorders, diabetes mellitus, and cancer. Early interventional data indicate that letermovir can reduce inflammation and improve immune and frailty outcomes in PWH, while vaccines are advancing in clinical evaluation.

CMV is a modifiable driver of immune dysfunction and aging in PWH. Targeted antiviral, vaccine, and host-directed approaches may reduce multimorbidity and promote healthy aging, particularly in populations at greatest risk.

Cytomegalovirus (CMV) is nearly universal among people with HIV (PWH) and persists despite suppressive antiretroviral therapy (ART), driving chronic immune activation and accelerated biological aging.

CMV is mechanistically linked to clonal T-cell expansion, innate immune reprogramming, metabolic rewiring, and durable epigenetic imprinting.

Clinical consequences span multiple aging-related disorders, including frailty cardiovascular disease (CVD), cognitive decline, diabetes mellitus, and cancer.

Therapeutic strategies under evaluation include anti-CMV drugs like letermovir and vaccines.

Future directions emphasize precision, multimorbidity-focused interventions to extend healthspan in aging PWH.