Long-term Trajectories of C-Reactive Protein Among Men Living With and Without HIV Infection in the Multicenter AIDS Cohort Study

Abstract

Background: C-reactive protein (CRP) is an inflammatory biomarker associated with all-cause mortality and morbidities such as cardiovascular disease. CRP is increased with HIV infection and thought to increase with age, though trajectories of CRP with aging have not been well characterized. We investigated trajectories of CRP in men from the Multicenter AIDS Cohort Study, according to HIV infection and HIV viral load status.

Methods: CRP measurements from 12 250 serum samples, provided by 2132 men over a span of 30 years, were categorized by HIV status at sample collection: HIV uninfected (HIV-, n = 1717), HIV infected with undetectable RNA (HIV+ suppressed, n = 4075), and detectable HIV RNA (HIV+ detectable, n = 6458). Age-related trajectories of CRP were fit to multivariable linear mixed models; we tested for differences in trajectories by HIV status.

Results: CRP increased with age in all sample groups. HIV+ detectable and HIV+ suppressed samples had higher CRP than HIV- samples throughout the observed age range of 20-70 years (p < .05). CRP concentrations at age 45 years were 38% (95% CI: 26%-50%) and 26% (15%-38%) higher in HIV+ detectable and HIV+ suppressed samples, respectively, relative to HIV- samples. HIV+ detectable samples showed more rapid linear increases with age (8% higher/decade, 0.3%-16%) than HIV- samples.

Conclusions: We observed higher concentrations of CRP across 5 decades of age in men living with HIV, and steeper increases with age in men with detectable HIV RNA, relative to HIV- men. These results are consistent with a contribution of inflammation to the higher risk of age-related comorbidities with HIV infection.

Keywords: Aging; Biomarkers; CRP; Inflammation; Longitudinal.

Figure 1.

(A) C-reactive protein (CRP) distributions in samples by HIV category. (B) CRP distributions in samples by decade of age, stratified by HIV category. Data are shown as violin plots with quartiles shaded by color and width representing density. Black diamonds indicate 25th, 50th, and 75th percentiles. Red diamonds indicate means. Vertical labels on left indicate ln values, and labels on right indicate linear values.

Figure 2.

Predicted C-reactive protein (CRP) concentrations across age, by HIV category, from linear mixed-effects model. Transparent bands represent 95% confidence intervals. Predicted values are displayed for men with reference values of covariates in model (White race, nonsmoking, not using injection drugs, no HCV infection, no obesity, no diabetes, no hypertension).