The effect of HAART-induced HIV suppression on circulating markers of inflammation and immune activation

Abstract

Objectives To investigate the impact of HAART-induced HIV suppression on levels of 24 serological biomarkers of inflammation and immune activation. Design Prospective cohort study. Methods Biomarkers were measured with multiplex assays in centralized laboratories using stored serum samples contributed by 1,697 men during 8,903 person-visits in the Multicenter AIDS Cohort Study (MACS) from 1984–2009. Using generalized gamma models, we compared biomarker values across three groups, adjusting for possible confounders: HIV-uninfected (NEG); HIV+, HAART-naïve (NAI); and HAART-exposed with HIV RNA suppressed to <50 copies/mL plasma (SUP). We also estimated changes in biomarker levels associated with duration of HIV suppression, using splined generalized gamma regression with a knot at one year. Results Most biomarkers were relatively normalized in the SUP group relative to the NAI group; however, 12 biomarkers in the SUP group were distinct (p<0.002) from NEG values: CXCL10, CRP, sCD14, sTNFR2, TNF-α, sCD27, sGP130, IL-8, CCL13, BAFF, GM-CSF, and IL-12p70. Thirteen biomarkers exhibited significant changes in the first year after viral suppression, but none changed significantly after that time. Conclusions Biomarkers of inflammation and immune activation moved toward HIV-negative levels within the first year after HAART-induced HIV suppression. Although several markers of T cell activation returned to levels present in HIV-negative men, residual immune activation, particularly monocyte/macrophage activation, was present. This residual immune activation may represent a therapeutic target to improve the prognosis of HIV-infected individuals receiving HAART.

Inflammatory Biomarkers and Mortality Risk Among HIV-Suppressed Men: A Multisite Prospective Cohort Study

“…Concentrations of serological biomarkers of inflammation and immune activation are higher in individuals with untreated HIV infection than in HIV-uninfected individuals [8]. Suppressive cART diminishes inflammation, but not all biomarkers return to the lower concentrations observed in HIVuninfected individuals [9,10]. Residual chronic inflammation and immune activation may increase mortality risks among HIV-infected individuals receiving cART.…”

“…Serum samples from MACS participants were chosen for a study of biomarkers of inflammation and immune activation at 1-year intervals for men with a known date of seroconversion, from visits immediately before and after cART initiation (and at 2-year intervals thereafter) for all cART users and from a sample of HIV-uninfected men [10]. Serum concentrations of 24 biomarkers were measured in these samples.…”

Stem-loop binding protein is a multifaceted cellular regulator of HIV-1 replication

“…Conversely, SLBP levels were approximately 40% (P < 0.05) higher in the low-VL versus the high-VL group ( Figure 6D). This prompted us to quantify SLBP levels in 2 additional cohorts of 43 individuals with low to undetectable levels of plasma TNF-α: seronegative individuals and those treated with suppressive antiretroviral medications (53). As seen in Figure 6D, SLBP levels in both of these cohorts were similar to that observed in the low-VL group, supporting the link between plasma TNF-α levels and intracellular SLBP protein expression.…”

Inflammation and Immune Activation in Antiretroviral-Treated Human Immunodeficiency Virus Type 1–Infected African Infants and Rotavirus Vaccine Responses

“…Cytokines commonly used to assess the inflammatory state in adult HIV-1 infection [7] 13], and tumor necrosis factor α [TNFα]) were quantified at study entry (prevaccination) and 21 days after the first vaccine dose using the ultrasensitive 10-plex human cytokine kit (V-Plex Proinflammatory Kit) from Meso-Scale Discoveries (Rockville, MD). Testing at additional time points was not performed due to lack of sample availability for the entire cohort.…”