TY - JOUR
T1 - The effect of HAART-induced HIV suppression on circulating markers of inflammation and immune activation
AU - Wada, Nikolas Itaru
AU - Jacobson, Lisa P.
AU - Margolick, Joseph B.
AU - Breen, Elizabeth Crabb
AU - Macatangay, Bernard
AU - Penugonda, Sudhir
AU - Martínez-Maza, Otoniel
AU - Bream, Jay H.
N1 - Publisher Copyright:
Copyright © 2015 Wolters Kluwer Health, Inc. All rights reserved.
PY - 2015/2/20
Y1 - 2015/2/20
N2 - OBJECTIVES:: To investigate the impact of HAART-induced HIV suppression on levels of 24 serological biomarkers of inflammation and immune activation. DESIGN:: A prospective cohort study. METHODS:: 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 50copies/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. 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, 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. CONCLUSION:: 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..
AB - OBJECTIVES:: To investigate the impact of HAART-induced HIV suppression on levels of 24 serological biomarkers of inflammation and immune activation. DESIGN:: A prospective cohort study. METHODS:: 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 50copies/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. 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, 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. CONCLUSION:: 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..
KW - AIDS
KW - antiretroviral therapy
KW - biological markers
KW - inflammation
KW - male
KW - prospective studies
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U2 - 10.1097/QAD.0000000000000545
DO - 10.1097/QAD.0000000000000545
M3 - Article
C2 - 25630041
AN - SCOPUS:84922284220
SN - 0269-9370
VL - 29
SP - 463
EP - 471
JO - AIDS
JF - AIDS
IS - 4
ER -