Recent clinical research highlights the NF-κB p65 biomarker as a superior tool for monitoring low-grade inflammation in people living with HIV-1 (PWH) who are receiving antiretroviral therapy (ART). While ART effectively suppresses viral replication, many patients continue to experience chronic, subclinical inflammation. This persistent state significantly increases the risk of non-communicable diseases, including cardiovascular issues and metabolic disorders. Consequently, clinicians need more precise diagnostic markers to evaluate these risks beyond traditional tests like high-sensitive C-reactive protein (HS-CRP).

Predictive Power of the NF-κB p65 Biomarker

An exploratory cross-sectional study involving 60 virally suppressed individuals and 60 controls demonstrated that NF-κB p65 levels are significantly elevated in PWH. Interestingly, the research utilized multivariable logistic regression and principal component analysis (PCA) to compare its efficacy against HS-CRP. The results showed that the NF-κB p65 biomarker achieved an Area Under the Curve (AUC) of 0.81, which is notably higher than the 0.70 recorded for HS-CRP. This suggests that NF-κB p65 provides a more accurate prediction of inflammatory status in stable HIV patients.

Moreover, k-means clustering and decision curve analysis further validated the clinical utility of this marker. Higher levels of NF-κB p65 were associated with increased inflammatory signaling, even when viral loads remained undetectable. Therefore, incorporating this specialized monitoring into routine clinical practice could help identify patients at higher risk for chronic complications. This proactive approach allows for earlier intervention and better management of long-term health outcomes in the ART-treated population.

Improving Clinical Outcomes in PWH

Effective management of HIV today extends far beyond viral suppression. Because low-grade inflammation persists, it remains a silent driver of morbidity and mortality. By shifting focus toward more sensitive markers like NF-κB p65, medical professionals can refine their risk assessment strategies. Additionally, this shift supports the potential development of targeted anti-inflammatory therapies. Ultimately, better monitoring leads to an improved quality of life for those living with HIV-1.

Frequently Asked Questions

Why is NF-κB p65 a better marker than HS-CRP for HIV patients?

NF-κB p65 specifically reflects the activation of the nuclear factor-kappa B pathway, which is central to HIV-related immune activation. The study showed it has a higher predictive performance (AUC 0.81) compared to the more general HS-CRP (AUC 0.70).

Can inflammation persist even if the viral load is undetectable?

Yes, many people living with HIV experience chronic low-grade inflammation despite successful viral suppression through ART. This ongoing immune activation is linked to various non-AIDS-related comorbidities like heart and renal disease.

Disclaimer: This content is for informational and educational purposes only. It does not constitute medical advice or a professional relationship. Always seek the advice of a qualified healthcare provider for any medical concerns or treatment. Refer to the latest local and national guidelines for clinical practice.

References

Gnanaskandan S et al. NF-κB p65 as a predictive biomarker of low-grade inflammation in ART-treated HIV-1 infection: comparison with HS-CRP. Biomark Med. 2026 Feb 14. doi: 10.1080/17520363.2026.2628972. PMID: 41689410.

Deeks SG et al. Immune Activation and Inflammation Among People With HIV Receiving Antiretroviral Therapy. NIH Clinical Guidelines. 2025.

Hunt PW. The inflammation hypothesis of non-AIDS events in treated HIV infection. J Infect Dis. 2014;210 Suppl 2:S572-81.