Human Immunodeficiency Virus Is Associated With Higher Levels of Systemic Inflammation Among Kenyan Adults Despite Viral Suppression

Abstract

Background Systemic inflammation independently predicts future cardiovascular events and is associated with a 2-fold increase in cardiovascular disease (CVD) risk among persons living with human immunodeficiency virus (PLHIV). We examined the association between inflammatory markers, HIV status, and traditional CVD risk factors. Methods We conducted a cross-sectional study of Kenyan adults with and without HIV seeking care at Kisumu County Hospital. Using a multiplex immunoassay, we measured interleukin (IL) 1β, IL-6, tumor necrosis factor α (TNF-α), and high-sensitivity C-reactive protein (hsCRP) concentrations. We compared inflammatory marker concentrations by HIV status using the Wilcoxon rank-sum test. Multivariable linear regression was used to evaluate associations between inflammatory biomarkers and HIV status, adjusting for CVD risk factors. Results We enrolled 286 PLHIV and 277 HIV-negative participants. Median duration of antiretroviral therapy for PLHIV was 8 years (interquartile range, 4–10) and 96% were virally suppressed. PLHIV had a 51% higher mean IL-6 concentration (P < .001), 39% higher mean IL-1β (P = .005), 40% higher mean TNF-α (P < .001), and 27% higher mean hsCRP (P = .008) compared with HIV-negative participants, independent of CVD risk factors. Male sex, older age, and obesity were associated with higher concentrations of inflammatory markers. Restricting to PLHIV, viral load of ≥1000 copies/mL was associated with higher TNF-α levels (P = .013). Conclusions We found higher levels of systemic inflammatory biomarkers among PLHIV who were virally suppressed, and this was independent of traditional CVD risk factors. Further longitudinal analyses to determine whether these inflammatory markers predict future CVD events, and are possible therapeutic targets among PLHIV, are warranted.

Central obesity is a contributor to systemic inflammation and monocyte activation in virally suppressed adults with chronic HIV in Kenya

“…We have previously shown that HIV was associated with greater inflammation and immune activation in our study cohort [ 10 , 16 ]. The present study expands on our data and those from prior studies in the USA and Europe that found greater inflammation and monocyte/macrophage activation among obese PWH [ 12 , 19 – 21 ].…”

“…Models were adjusted for demographic characteristics (age and sex), and traditional CVD risk factors (hypertension, hypercholesterolemia and alcohol use status) and further adjusted for BMI. These covariates were selected based on prior work suggesting an association between covariates and the biomarkers [ 10 , 16 , 41 ]. Multivariable models were sequentially adjusted for each of the biomarkers; I-FABP, sCD14 and sCD163, respectively.…”

“…Elevated levels of pro-inflammatory cytokines [interleukin (IL)-1 b, IL -6, tumour necrosis factor (TNF)-a and high-sensitivity C-reactive protein (hsCRP)] and monocyte activation biomarkers [soluble CD163 (sCD163) and sCD14] are associated with an increased risk of developing CVD [9][10][11][12][13][14][15][16][17]. We have recently shown that African PWH and the obese adults exhibit high levels of these biomarkers even after ART compared with the noninfected adults [10,16]. The pathophysiology of HIVassociated immune activation and inflammation is still unclear and may be multifactorial; however, hsCRP has been shown to correlate with visceral fat mass in PWH implying that visceral adiposity may be a risk factor [18].…”

The role of IL‐1β during human immunodeficiency virus type 1 infection

“…186,187 In line with these results, a recent study conducted by Masyuko et al, who enroled 286 HIV-1 positive Kenyan adults with suppressive ART for several years, reported that HIV-1 patients express higher serum levels of the inflammatory cytokines IL-1β, IL-6, TNF-α than the uninfected controls, even when the virus is fully suppressed. 188 On the contrary, other studies showed that treatment with ART has no effect on decreasing the expression of several proinflammatory cytokines including IL-1β. 185 The latter could be attributed, at least in part, to the notion that during the chronic phase of HIV-1 infection, certain inflammatory pathways and cytokines are not continually amplified.…”

Different Trends of Distinct Time Points of AIDS Events Following HIV Diagnosis in Various At-risk Populations: A Retrospective Nationwide Cohort Study in Taiwan

“…Acquired immune deficiency syndrome (AIDS) is a chronic, potentially life-threatening, immunocompromised status caused by human immunodeficiency virus (HIV) [ 1 ]. In addition to morbidity and mortality [ 2 – 7 ], AIDS events are associated with negative outcomes, such as relatively high rates of HIV transmission to sexual partners [ 8 , 9 ], relatively high rates of treatment failure after combination antiretroviral therapy (cART) [ 10 ], a poor immunological response to cART [ 11 ], and possible neurological sequelae [ 12 ]. Therefore, surveying the trends of AIDS incidence in persons with HIV (PWH) and characterizing the determinants of AIDS events are essential to HIV care.…”