Shifting the Narrative on HIV-Related Inflammation

People living with HIV (PLWH) on antiretroviral therapy (ART) often experience chronic inflammation, an immune response that may contribute to accelerated heart disease and neurocognitive disorders, among other conditions.

Researchers now have a greater understanding of chronic inflammation as it relates to HIV, thanks to a new study co-authored by amfAR grantee Dr. Alexander O. Pasternak of the University of Amsterdam.

Early studies

Several studies early in the AIDS pandemic supported the concept that the HIV reservoir—mostly inactive HIV-infected cells that persist beyond the reach of ART—is not only the principal impediment to an HIV cure but also the primary driver of inflammation.

But in an age where more potent ART regimens are initiated much earlier after HIV infection, leading to smaller reservoirs and less residual HIV activity, the importance of HIV persistence to chronic immune activation is in dispute.

No significant correlations

In Dr. Pasternak’s study, 49 adults treated for at least two years with integrase-inhibitor-based ART were evaluated. No significant correlations were found between markers of latent HIV or residual, low-level HIV replication and markers of inflammation.

The authors concluded that today’s PLWH, “treated earlier with more potent regimens, have smaller, less active [HIV] reservoirs that exert a diminished impact on immune activation.”

Implications

These findings are important: If inflammation was primarily driven by HIV reservoir size, then therapeutic strategies should focus on suppression of this cell population. Given the lack of such a correlation in the contemporary cohort of PLWH, greater focus on other drivers of inflammation, from obesity and smoking to co-infections and the gut microbiome, should be considered.

One exception, related to immune cell populations, was that levels of residual virus did negatively correlate with levels of natural killer (NK) cells. This finding underscores a key role for NK cells in HIV reservoir dynamics, a focus of recent amfAR cure-related grants.

Original article
http://www.ncbi.nlm.nih.gov/pubmed/40791593

Dr. Laurence is amfAR’s senior scientific consultant.

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