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

TLDR

The study examined how HAART‑induced HIV suppression affects 24 inflammatory and immune activation biomarkers in a prospective cohort of 1697 men. Researchers measured these biomarkers with multiplex assays on stored serum from 1697 men in the MACS cohort and used generalized gamma models to compare levels among HIV‑negative, HAART‑naïve, and virologically suppressed groups, adjusting for confounders and modeling changes over time. After viral suppression, most biomarkers approached HIV‑negative levels within a year, but 12 remained elevated and 13 changed only in the first year, with residual monocyte/macrophage activation persisting as a potential therapeutic target.

Abstract

To investigate the impact of HAART-induced HIV suppression on levels of 24 serological biomarkers of inflammation and immune activation.A prospective cohort study.Biomarkers were measured with multiplex assays in centralized laboratories using stored serum samples contributed by 1697 men during 8903 person-visits in the Multicenter AIDS Cohort Study (MACS) from 1984 to 2009. Using generalized gamma models, we compared biomarker values across three groups, adjusting for possible confounders: HIV-uninfected (NEG); HIV-positive, HAART-naive (NAI); and HAART-exposed with HIV RNA suppressed to less than 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 1 year.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, C-reactive protein (CRP), sCD14, sTNFR2, tumour necrosis factor-alpha (TNF-α), sCD27, sGP130, interleukin (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.Biomarkers of inflammation and immune activation moved towards 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.