Title | 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. |
Publication Type | Journal Article |
Year of Publication | 2014 |
Authors | McComsey GA, Kitch D, Sax PE, Tierney C, Jahed NC, Melbourne K, Ha B, Brown TT, Bloom A, Fedarko N, Daar ES |
Journal | J Acquir Immune Defic Syndr |
Volume | 65 |
Issue | 2 |
Pagination | 167-74 |
Date Published | 2014 Feb 1 |
ISSN | 1944-7884 |
Keywords | Acquired 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. |
DOI | 10.1097/01.qai.0000437171.00504.41 |
Alternate Journal | J. Acquir. Immune Defic. Syndr. |
PubMed ID | 24121755 |
PubMed Central ID | PMC3943548 |
Grant List | AI065348 / 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 |