Abstract
Low-grade inflammation in people living with HIV (PWH) has become a significant contributor to the development of non-communicable diseases (NCDs) such as heart disease, stroke, and renal dysfunction. Though antiretroviral therapy (ART) has dramatically reduced mortality by limiting the emergence of opportunistic infections, it has not been successful in eliminating the remaining chronic, low-grade inflammation and activation that persists in the infected despite viral suppression and better CD4+ T cell count. Nonetheless, this relatively asymptomatic and subclinical chronic inflammation remains poorly understood and has become a major contributor to mortality in PWH. Another important component involved in this step is the Nuclear Factor kappa B (NF-κB) which is a central transcription factor in the immune system to respond to infection. Specifically, the p65/RELA subunit attaches to the HIV LTR (long terminal repeat) gene and consequently initiates the synthesis of genes related to inflammation and immune reactions. Persistent low-level chronic inflammation contributes to the pathophysiology of metabolic-inflammatory NCDs. Therefore, this review aims to assess the complex contextual function of NF-κB p65 during HIV-1 disease, particularly among individuals on ART who achieve viral suppression. As much as ART has helped to arrest the progression of the virus, immune function, and chronic inflammation have not been reversed in most PWH. It is, therefore, pertinent to know how the NF-κB p65 molecule remains involved in those with persistent immune inflammation concerns to enhance strategies on the same. This review will also discuss the possible variation in NF-κB p65 activity in particular population groups such as MSM (men who have sex with men) to acquire additional information that could potentially enhance the treatment.