Understanding the nuances of HIV immune dysregulation is vital for managing heavily treatment-experienced (HTE) patients. Indeed, a recent study from the Prestigio Registry provides new insights into this complex issue. Specifically, researchers compared individuals who acquired HIV through vertical transmission (VT) with those who acquired it horizontally (HT). Previously, many expected lifelong exposure in the VT group to result in higher inflammatory markers. However, the data reveals a different story.

The study specifically focused on markers of inflammation and T-cell activation, exhaustion, and senescence. Overall, heavily treatment-experienced individuals carry a high inflammatory burden compared to people without HIV. Interestingly, the research showed that Interleukin-6 (IL-6) levels were actually lower in the VT group. Essentially, this finding occurred because the VT participants were significantly younger than their HT counterparts. Consequently, age emerged as a primary factor positively correlating with IL-6 levels.

The Role of Age in HIV Immune Dysregulation

Furthermore, the mode of transmission did not independently dictate the severity of immune impairment. Instead, age and ongoing viral replication appeared as the main drivers of T-cell dysfunction. Specifically, both viremic VT and HT individuals displayed greater T-cell senescence and exhaustion. In fact, these findings highlight that persistent viral exposure from birth does not necessarily lead to worse immune outcomes than adult-acquired HIV. Therefore, clinical focus should remain on achieving viral suppression and managing age-related health issues.

Additionally, the researchers noted that T-cell dysfunction was significantly higher in all HTE individuals than in HIV-negative controls. Similarly, this disparity suggests that even with treatment, HTE patients face unique immunological challenges. Thus, clinicians must prioritize robust antiretroviral strategies to minimize viral replication. Moreover, addressing age-associated inflammation remains a critical component of long-term care for this population.

Frequently Asked Questions

Does vertical HIV acquisition cause more inflammation in HTE patients?

Interestingly, no. Research indicates that transmission mode is not the primary driver. Instead, older age and active viral replication contribute more significantly to inflammation in heavily treatment-experienced individuals.

How does viral replication affect T-cell function?

Specifically, ongoing viral replication leads to higher levels of T-cell activation and exhaustion. Therefore, achieving complete viral suppression is essential to mitigate these aspects of immune dysfunction in the HTE population.

Disclaimer: This content is for informational and educational purposes only and does not constitute medical advice or a professional relationship between the reader and the author. While we strive to provide accurate and up-to-date information, the field of medicine is constantly evolving. Refer to the latest local and national guidelines for clinical practice.

References

1. Bono V et al. Age and viral replication, not vertical HIV acquisition, drive inflammation and T-cell dysfunction in heavily treatment experienced: data from the Prestigio Registry. AIDS. 2026 May 01. doi: 10.1097/QAD.0000000000004415. PMID: 41891217.


2. Clemente T et al. Inflammation burden score in multidrug-resistant HIV-1 infection. ICAR 2026.


3. Pelchen-Matthews A et al. Prevalence and Outcomes for Heavily Treatment-Experienced (HTE) Individuals Living with Human Immunodeficiency Virus in a European Cohort. JAIDS. 2021.