TY - JOUR
T1 - Continued elevation of interleukin-18 and interferon-γ after initiation of antiretroviral therapy and clinical failure in a diverse multicountry human immunodeficiency virus cohort
AU - for the New Works Concept Sheet 319 and AIDS Clinical Trials Group 5175 Study Teams
AU - Balagopal, Ashwin
AU - Gupte, Nikhil
AU - Shivakoti, Rupak
AU - Cox, Andrea L.
AU - Yang, Wei Teng
AU - Berendes, Sima
AU - Mwelase, Noluthando
AU - Kanyama, Cecilia
AU - Pillay, Sandy
AU - Samaneka, Wadzanai
AU - Santos, Breno
AU - Poongulali, Selvamuthu
AU - Tripathy, Srikanth
AU - Riviere, Cynthia
AU - Lama, Javier R.
AU - Cardoso, Sandra W.
AU - Sugandhavesa, Patcharaphan
AU - Semba, Richard D.
AU - Hakim, James
AU - Hosseinipour, Mina C.
AU - Kumarasamy, Nagalingeswaran
AU - Sanne, Ian
AU - Asmuth, David
AU - Campbell, Thomas
AU - Bollinger, Robert C.
AU - Gupta, Amita
N1 - Publisher Copyright:
© The Author 2016.
PY - 2016/5/1
Y1 - 2016/5/1
N2 - Background. We assessed immune activation after antiretroviral therapy (ART) initiation to understand clinical failure in diverse settings. Methods. We performed a case-control study in ACTG Prospective Evaluation of Antiretrovirals in Resource-Limited Settings (PEARLS). Cases were defined as incidentWorld Health Organization Stage 3 or 4 human immunodeficiency virus (HIV) disease or death, analyzed from ART weeks 24 (ART24) to 96. Controls were randomly selected. Interleukin (IL)-6, interferon (IFN)-γ-inducible protein-10, IL-18, tumor necrosis factor-α, IFN-γ, and soluble CD14 (sCD14) were measured pre-ART and at ART24 in plasma. Continued elevation was defined by thresholds set by highest pre-ART quartiles (>Q3). Incident risk ratios (IRRs) for clinical progression were estimated by Poisson regression, adjusting for age, sex, treatment, country, time-updated CD4+ T-cell count, HIV ribonucleic acid (RNA), and prevalent tuberculosis. Results. Among 99 cases and 234 controls, median baseline CD4+ T-cell count was 181 cells/μL, and HIV RNA was 5.05 log10 cp/mL. Clinical failure was independently associated with continued elevations of IL-18 (IRR, 3.03; 95% confidence interval [CI], 1.27-7.20), sCD14 (IRR, 2.17; 95% CI, 1.02-4.62), and IFN-γ (IRR, 0.08; 95% CI, 0.01-0.61). Among 276 of 333 (83%) who were virologically suppressed at ART24, IFN-γ was associated with protection from failure, but the association with sCD14 was attenuated. Conclusions. Continued IL-18 and sCD14 elevations were associated with clinical ART failure. Interferon-γ levels may reflect preserved immune function.
AB - Background. We assessed immune activation after antiretroviral therapy (ART) initiation to understand clinical failure in diverse settings. Methods. We performed a case-control study in ACTG Prospective Evaluation of Antiretrovirals in Resource-Limited Settings (PEARLS). Cases were defined as incidentWorld Health Organization Stage 3 or 4 human immunodeficiency virus (HIV) disease or death, analyzed from ART weeks 24 (ART24) to 96. Controls were randomly selected. Interleukin (IL)-6, interferon (IFN)-γ-inducible protein-10, IL-18, tumor necrosis factor-α, IFN-γ, and soluble CD14 (sCD14) were measured pre-ART and at ART24 in plasma. Continued elevation was defined by thresholds set by highest pre-ART quartiles (>Q3). Incident risk ratios (IRRs) for clinical progression were estimated by Poisson regression, adjusting for age, sex, treatment, country, time-updated CD4+ T-cell count, HIV ribonucleic acid (RNA), and prevalent tuberculosis. Results. Among 99 cases and 234 controls, median baseline CD4+ T-cell count was 181 cells/μL, and HIV RNA was 5.05 log10 cp/mL. Clinical failure was independently associated with continued elevations of IL-18 (IRR, 3.03; 95% confidence interval [CI], 1.27-7.20), sCD14 (IRR, 2.17; 95% CI, 1.02-4.62), and IFN-γ (IRR, 0.08; 95% CI, 0.01-0.61). Among 276 of 333 (83%) who were virologically suppressed at ART24, IFN-γ was associated with protection from failure, but the association with sCD14 was attenuated. Conclusions. Continued IL-18 and sCD14 elevations were associated with clinical ART failure. Interferon-γ levels may reflect preserved immune function.
KW - Antiretroviral therapy
KW - HIV
KW - IFN-γ
KW - IL-18
KW - Immune activation
KW - Inflammasome
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U2 - 10.1093/ofid/ofw118
DO - 10.1093/ofid/ofw118
M3 - Article
C2 - 27800521
AN - SCOPUS:85015845113
SN - 2328-8957
VL - 3
JO - Open Forum Infectious Diseases
JF - Open Forum Infectious Diseases
IS - 3
ER -