University of Nairobi/University of Washington
Clinical Assistant Professor
Objectives: Heightened systemic inflammation is common in obese individuals and persons with HIV (PWH) and is independently associated with an increased risk of cardiovascular diseases (CVD). We investigated the combined effect of central obesity, a surrogate measure of visceral fat, and HIV on circulating levels of inflammatory cytokines among Kenyan adults.
Design: Cross-sectional study.
Methods: We analyzed and compared data from 287 virally suppressed PWH and 277 non-infected Kenyan adults including biomarkers of gut epithelial dysfunction (intestinal fatty acid binding protein), monocyte activation (soluble CD163 and CD14), and inflammation (interleukin [IL]-1β, IL-6, TNF-α, and hsCRP) by HIV/central obesity status (HIV+/obese, HIV-/obese, HIV+/non-obese, and HIV-/non-obese). Central obesity was defined as waist circumference >80 cm for women and >94 cm for men. We assessed the association of HIV/obesity status with elevated biomarkers (>75th percentile) using logistic regression.
Results: Median age for participants was 44 years and 37% were centrally obese. Levels of all biomarkers were higher among the HIV+/obese compared to the HIV-/non-obese (p < 0.05 for all comparisons). The HIV+/obese group had the greatest odds of having elevated inflammatory biomarkers compared to other groups even after adjustment of age, BMI, and other conventional CVD risk factors (p < 0.05 for all). Additional adjustment for sCD163 in the multivariate model substantially attenuated the association for HIV+/obesity with IL-1β, IL-6, and TNF-α but not hsCRP. The contribution of HIV+/obesity to inflammation was independent of the degree of immunosuppression.
Conclusions: Central obesity is prevalent among virally suppressed African PWH and is associated with greater inflammation and monocyte activation independent of other comorbidities and HIV-specific factors.
Introduction: Markers of monocyte/macrophage activation and vascular inflammation are associated with HIV-related cardiovascular diseases (CVD) and mortality. We compared these markers among African people living with HIV (PLWH) and HIV-negative adults, and examined risk factors associated with elevated biomarkers (>75th percentile) in PLWH on antiretroviral therapy (ART).
Design: Cross-sectional study.
Methods: We measured serum concentrations of a gut integrity biomarker (intestinal-fatty acid binding protein), monocyte/macrophage activation biomarkers (soluble CD14 and CD163), and vascular inflammation biomarkers [soluble intercellular adhesion molecule 1 (sICAM-1) and soluble vascular adhesion molecule 1 (sVCAM-1)]. We assessed the relationship of these inflammatory parameters with HIV, using logistic regression adjusting for traditional CVD risk factors.
Results: Among the 541 participants, median age was 43 years and half were female. Among 275 PLWH, median CD4 T-cell count and duration of ART use was 509 cells/μl and 8 years, respectively. PLWH had significantly higher prevalence of elevated inflammatory biomarkers compared with HIV-negative individuals even after adjustment for traditional CVD risk factors. Compared with individuals without HIV, the prevalence of elevated biomarkers was highest among persons with detectable viral load and CD4 T-cell counts 200 cells/μl or less. In a subanalysis among PLWH, nadir CD4 T-cell count 200 cells/μl or less was associated with elevated soluble CD14 (sCD14); dyslipidemia with elevated sCD14, sICAM-1, and sVCAM-1; and overweight/obesity with reduced sCD14. Longer ART exposure (>4 years) was associated with reduced sVCAM-1 and sICAM-1.
Conclusion: HIV and not traditional CVD risk factors is a primary contributor of monocyte/macrophage activation and inflammation despite ART. Anti-inflammatory therapies in addition to ART may be necessary to reduce these immune dysregulations and improve health outcomes of African PLWH.