TY - JOUR
T1 - Associations of inflammatory markers with AIDS and non-AIDS clinical events after initiation of antiretroviral therapy
T2 - AIDS clinical trials group A5224s, a substudy of ACTG A5202
AU - McComsey, Grace A.
AU - Kitch, Douglas
AU - Sax, Paul E.
AU - Tierney, Camlin
AU - Jahed, Nasreen C.
AU - Melbourne, Kathleen
AU - Ha, Belinda
AU - Brown, Todd T.
AU - Bloom, Anthony
AU - Fedarko, Neal
AU - Daar, Eric S.
PY - 2014
Y1 - 2014
N2 - Background: The association of inflammatory biomarkers with clinical events after antiretroviral therapy initiation is unclear. Methods: A5202 randomized 1857 treatment-naive subjects to abacavir/lamivudine or tenofovir-DF/ emtricitabine with efavirenz or atazanavir/ritonavir. Substudy A5224s measured inflammatory biomarkers on subjects with available plasma from baseline and week 24 or 96. An exploratory analysis of the association of highsensitivity C-reactive protein, interleukin-6 (IL-6), soluble receptors of tumor necrosis factor a (sTNF)-RI, sTNF-RII, TNF-a, soluble vascular cellular adhesion molecules (sVCAM-1), and soluble intercellular adhesion molecules (sICAM-1) with times to AIDS and to non-AIDS events used Cox proportional hazards models. Results: Analysis included 244 subjects; 85% men and 48% white non-Hispanic with median age 39 years, HIV-1 RNA of 4.6 log10 copies per milliliter, and CD4 of 240 cells per microliter. Overall, 13 AIDS events (9 opportunistic infections, 3 AIDS-cancers, and 1 recurrent bacterial pneumonia) and 18 non-AIDS events (6 diabetes, 4 cancers, 3 cardiovascular, and 5 pneumonias) occurred. Higher baseline IL-6, sTNF-RI, sTNF-RII, and sICAM-1 were significantly associated with increased risk of AIDS-defining events. Adjustment for baseline HIV-1 RNA did not change results, whereas adjusting for baseline CD4 count left only sTNF-RI and sICAM-1 significantly associated with increased risk. Time-updated values of IL-6, sTNFR-I and II, and sICAM-1 were also associated with an increased risk. For non- AIDS events, only higher baseline high-sensitivity C-reactive protein was significantly associated with increased risk, whereas higher IL-6 was marginally associated with higher risk. Analyses of timeupdated biomarker values showed tumor necrosis factor a to be significantly associated with increased risk, even after adjustment for antiretroviral therapy, and CD4 count or HIV-1 RNA. Conclusions: Higher levels of several inflammatory biomarkers were independently associated with increased risk of AIDS and non- AIDS events.
AB - Background: The association of inflammatory biomarkers with clinical events after antiretroviral therapy initiation is unclear. Methods: A5202 randomized 1857 treatment-naive subjects to abacavir/lamivudine or tenofovir-DF/ emtricitabine with efavirenz or atazanavir/ritonavir. Substudy A5224s measured inflammatory biomarkers on subjects with available plasma from baseline and week 24 or 96. An exploratory analysis of the association of highsensitivity C-reactive protein, interleukin-6 (IL-6), soluble receptors of tumor necrosis factor a (sTNF)-RI, sTNF-RII, TNF-a, soluble vascular cellular adhesion molecules (sVCAM-1), and soluble intercellular adhesion molecules (sICAM-1) with times to AIDS and to non-AIDS events used Cox proportional hazards models. Results: Analysis included 244 subjects; 85% men and 48% white non-Hispanic with median age 39 years, HIV-1 RNA of 4.6 log10 copies per milliliter, and CD4 of 240 cells per microliter. Overall, 13 AIDS events (9 opportunistic infections, 3 AIDS-cancers, and 1 recurrent bacterial pneumonia) and 18 non-AIDS events (6 diabetes, 4 cancers, 3 cardiovascular, and 5 pneumonias) occurred. Higher baseline IL-6, sTNF-RI, sTNF-RII, and sICAM-1 were significantly associated with increased risk of AIDS-defining events. Adjustment for baseline HIV-1 RNA did not change results, whereas adjusting for baseline CD4 count left only sTNF-RI and sICAM-1 significantly associated with increased risk. Time-updated values of IL-6, sTNFR-I and II, and sICAM-1 were also associated with an increased risk. For non- AIDS events, only higher baseline high-sensitivity C-reactive protein was significantly associated with increased risk, whereas higher IL-6 was marginally associated with higher risk. Analyses of timeupdated biomarker values showed tumor necrosis factor a to be significantly associated with increased risk, even after adjustment for antiretroviral therapy, and CD4 count or HIV-1 RNA. Conclusions: Higher levels of several inflammatory biomarkers were independently associated with increased risk of AIDS and non- AIDS events.
KW - AIDS events
KW - C-reactive protein
KW - Endothelial activation markers
KW - Inflammation markers
KW - Interleukin-6
KW - Non-AIDS events
KW - TNF-α
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U2 - 10.1097/01.qai.0000437171.00504.41
DO - 10.1097/01.qai.0000437171.00504.41
M3 - Article
C2 - 24121755
AN - SCOPUS:84893799273
SN - 1525-4135
VL - 65
SP - 167
EP - 174
JO - Journal of Acquired Immune Deficiency Syndromes
JF - Journal of Acquired Immune Deficiency Syndromes
IS - 2
ER -