Associations of inflammatory markers with AIDS and non-AIDS clinical events after initiation of antiretroviral therapy: AIDS clinical trials group A5224s, a substudy of ACTG A5202.

TitleAssociations of inflammatory markers with AIDS and non-AIDS clinical events after initiation of antiretroviral therapy: AIDS clinical trials group A5224s, a substudy of ACTG A5202.
Publication TypeJournal Article
Year of Publication2014
AuthorsMcComsey GA, Kitch D, Sax PE, Tierney C, Jahed NC, Melbourne K, Ha B, Brown TT, Bloom A, Fedarko N, Daar ES
JournalJ Acquir Immune Defic Syndr
Volume65
Issue2
Pagination167-74
Date Published2014 Feb 1
ISSN1944-7884
KeywordsAcquired Immunodeficiency Syndrome, Adolescent, Adult, Anti-Retroviral Agents, Antiretroviral Therapy, Highly Active, Biomarkers, Female, Humans, Inflammation, Male, Middle Aged, Young Adult
Abstract

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 high-sensitivity C-reactive protein, interleukin-6 (IL-6), soluble receptors of tumor necrosis factor α (sTNF)-RI, sTNF-RII, TNF-α, 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 time-updated biomarker values showed tumor necrosis factor α 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.

DOI10.1097/01.qai.0000437171.00504.41
Alternate JournalJ. Acquir. Immune Defic. Syndr.
PubMed ID24121755
PubMed Central IDPMC3943548
Grant ListAI065348 / AI / NIAID NIH HHS / United States
AI068634 / AI / NIAID NIH HHS / United States
AI38855 / AI / NIAID NIH HHS / United States
P30 AI036219 / AI / NIAID NIH HHS / United States
R01 AI065348 / AI / NIAID NIH HHS / United States
U01 AI038855 / AI / NIAID NIH HHS / United States
U01 AI068634 / AI / NIAID NIH HHS / United States
U01 AI068636 / AI / NIAID NIH HHS / United States
U01 AI069472 / AI / NIAID NIH HHS / United States
U01 AI069501 / AI / NIAID NIH HHS / United States
U01AI068636 / AI / NIAID NIH HHS / United States
UL1 TR000124 / TR / NCATS NIH HHS / United States
UL1 TR000457 / TR / NCATS NIH HHS / United States
UM1 AI068634 / AI / NIAID NIH HHS / United States
UM1 AI068636 / AI / NIAID NIH HHS / United States
UM1 AI069412 / AI / NIAID NIH HHS / United States
UM1 AI069424 / AI / NIAID NIH HHS / United States
UM1 AI069501 / AI / NIAID NIH HHS / United States
UM1 AI106701 / AI / NIAID NIH HHS / United States