Plasma Biomarkers of Human Immunodeficiency Virus–Related Systemic Inflammation and Immune Activation in Sub-Saharan Africa Before and During Suppressive Antiretroviral Therapy

Abstract

We evaluated immune biomarker profiles in human immunodeficiency virus (HIV)–infected adults (n = 398) from 5 African countries. Although all biomarkers decreased after antiretroviral therapy (ART) initiation, levels of C-X-C chemokine ligand 10 (CXCL10), lipopolysaccharide-binding protein, C-reactive protein, soluble CD163, and soluble scavenger receptor CD14 were significantly higher during ART than in an HIV-uninfected reference group (n = 90), indicating persistent monocyte/macrophage activation, inflammation, and microbial translocation. Before ART initiation, high HIV viral load was associated with elevated CXCL10 and tuberculosis coinfection was associated with elevated soluble CD14. High pre-ART levels of each biomarker strongly predicted residual immune activation during ART. Chemokine (C-C motif) ligand 2, lipopolysaccharide-binding protein, C-reactive protein, and interleukin 6 were differentially expressed between countries. Further research is needed on the clinical implications of residual immune dysregulation.

Systemic Inflammation and the Increased Risk of Inflamm-Aging and Age-Associated Diseases in People Living With HIV on Long Term Suppressive Antiretroviral Therapy

“…Contradictory results have been reported from different studies on the effect of cART on sCD14 (33–35) due to a variety of contributors (36, 37). On the other hand, sCD163, a marker of vascular inflammation (38) and neurocognitive impairment (39), was higher in PLHIV than in healthy controls, which is in contrast to previous reports (40) but in line with other studies which showed that sCD163 was higher compared to the HIV-negative controls within 2 years of therapy (41, 42). The novelty of our study was to explore a large panel of inflammatory markers and we showed significantly higher levels of MMP1 (43), ADA (44), CD8A (16), SLAMF1 (45), and CCL23 (46) in PLHIV on long term ART.…”

An Inflammatory Story: Antibodies in Tuberculosis Comorbidities

“…In acute HIV-1 infection the viral load rapidly increases alongside a burst of cytokines such as IFN-α and overstimulated pro-apoptotic CD4+ T cells; the immunological hallmark of HIV-1 infection (157). There is mounting evidence that chronic HIV-1 disease progression is characterized by systemic immune activation and oxidative stress, which can occur even while viremia is controlled with antiretrovirals (158)(159)(160). This systemic inflammation is thought to be caused by a number of factors; namely gut permeability, activated monocytes and cytokine derangement (160)(161)(162)(163).…”

“…There is mounting evidence that chronic HIV-1 disease progression is characterized by systemic immune activation and oxidative stress, which can occur even while viremia is controlled with antiretrovirals (158)(159)(160). This systemic inflammation is thought to be caused by a number of factors; namely gut permeability, activated monocytes and cytokine derangement (160)(161)(162)(163). High levels of viremia are accompanied by high levels of IFN-γ, TNF-α, IFNα, and other inflammatory markers (164)(165)(166).…”

Incomplete immune reconstitution in HIV/AIDS patients on antiretroviral therapy: Challenges of immunological non-responders

“…During HIV-1 infection, persistent immune activation and inflammation are driven by multiple factors, including residual virus replication, inflammatory lipids, gut microbial translocation, and coinfection [92][93][94]. Although long-term effective ART substantially reduces the level of immune activation and inflammation in HIV-1-infected individuals, it fails to normalize the activation and inflammation [95][96][97][98][99]. It was reported that persistent T-cell activation was associated with decreased CD4 + T-cell gains in HIV-1-infected individuals during ART 53.…”