Continued elevation of interleukin-18 and interferon-γ after initiation of antiretroviral therapy and clinical failure in a diverse multicountry human immunodeficiency virus cohort

for the New Works Concept Sheet 319 and AIDS Clinical Trials Group 5175 Study Teams

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish (US)
Article numberofw118
JournalOpen Forum Infectious Diseases
Volume3
Issue number3
DOIs
StatePublished - 2016

Fingerprint

Interleukin-18
Interferons
HIV
Odds Ratio
Confidence Intervals
CD4 Lymphocyte Count
Chemokine CXCL10
RNA
T-Lymphocytes
Therapeutics
Virus Diseases
Case-Control Studies
Interleukin-6
Tuberculosis
Tumor Necrosis Factor-alpha
Health

Keywords

  • Antiretroviral therapy
  • HIV
  • IFN-γ
  • IL-18
  • Immune activation
  • Inflammasome

ASJC Scopus subject areas

  • Oncology
  • Clinical Neurology

Cite this

Continued elevation of interleukin-18 and interferon-γ after initiation of antiretroviral therapy and clinical failure in a diverse multicountry human immunodeficiency virus cohort. / for the New Works Concept Sheet 319 and AIDS Clinical Trials Group 5175 Study Teams.

In: Open Forum Infectious Diseases, Vol. 3, No. 3, ofw118, 2016.

Research output: Contribution to journalArticle

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title = "Continued elevation of interleukin-18 and interferon-γ after initiation of antiretroviral therapy and clinical failure in a diverse multicountry human immunodeficiency virus cohort",
abstract = "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.",
keywords = "Antiretroviral therapy, HIV, IFN-γ, IL-18, Immune activation, Inflammasome",
author = "{for the New Works Concept Sheet 319 and AIDS Clinical Trials Group 5175 Study Teams} and Ashwin Balagopal and Nikhil Gupte and Rupak Shivakoti and Andrea Cox and Yang, {Wei Teng} and Sima Berendes and Noluthando Mwelase and Cecilia Kanyama and Sandy Pillay and Wadzanai Samaneka and Breno Santos and Selvamuthu Poongulali and Srikanth Tripathy and Cynthia Riviere and Lama, {Javier R.} and Cardoso, {Sandra W.} and Patcharaphan Sugandhavesa and Semba, {Richard David} and James Hakim and Hosseinipour, {Mina C.} and Nagalingeswaran Kumarasamy and Ian Sanne and David Asmuth and Thomas Campbell and Bollinger, {Robert C} and Amita Gupta",
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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

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 David

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

PY - 2016

Y1 - 2016

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

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