Clinical and immunologic predictors of death after an acute opportunistic infection

Results from ACTG A5164

Philip Grant, Lauren Komarow, Alejandro Sanchez, Fred Sattler, David Asmuth, Richard B Pollard, Andrew Zolopa

Research output: Contribution to journalArticle

5 Citations (Scopus)

Abstract

Background: In the pre-antiretroviral therapy (ART) era, markers of increased disease severity during an acute opportunistic infection (OI) were associated with mortality. Even with ART, mortality remains high during the first year after an OI in persons with advanced HIV infection, but it is unclear whether previous predictors of mortality remain valid in the current era. Objective: To determine clinical and immunological predictors of death after an OI. Methods: We used clinical data and stored plasma from ACTG A5164, a multicenter study evaluating the optimal timing of ART during a nontuberculous OI. We developed Cox models evaluating associations between clinical parameters and plasma marker levels at entry and time to death over the first 48 weeks after the diagnosis of OI. We developed multivariable models incorporating only clinical parameters, only plasma marker levels, or both. Results: The median CD4+ T-cell count in study participants at baseline was 29 cells/μL. Sixty-four percent of subjects had Pneumocystis jirovecii pneumonia (PCP). Twenty-three of 282 (8.2%) subjects died. In univariate analyses, entry mycobacterial infection, OI number, hospitalization, low albumin, low hemoglobin, lower CD4, and higher IL-8 and sTNFrII levels and lower IL-17 levels were associated with mortality. In the combined model using both clinical and immunologic parameters, the presence of an entry mycobacterial infection and higher sTNFrII levels were significantly associated with death. Conclusions: In the ART era, clinical risk factors for death previously identified in the pre-ART era remain predictive. Additionally, activation of the innate immune system is associated with an increased risk of death following an acute OI.

Original languageEnglish (US)
Pages (from-to)133-139
Number of pages7
JournalHIV Clinical Trials
Volume15
Issue number4
DOIs
StatePublished - Jan 1 2014

Fingerprint

Opportunistic Infections
Mortality
Therapeutics
Pneumocystis carinii
Pneumocystis Pneumonia
Interleukin-17
CD4 Lymphocyte Count
Infection
Interleukin-8
Proportional Hazards Models
Multicenter Studies
HIV Infections
Albumins
Immune System
Hemoglobins
Hospitalization
T-Lymphocytes

Keywords

  • HIV infections/complications
  • mortality
  • opportunistic infections

ASJC Scopus subject areas

  • Infectious Diseases
  • Pharmacology (medical)

Cite this

Clinical and immunologic predictors of death after an acute opportunistic infection : Results from ACTG A5164. / Grant, Philip; Komarow, Lauren; Sanchez, Alejandro; Sattler, Fred; Asmuth, David; Pollard, Richard B; Zolopa, Andrew.

In: HIV Clinical Trials, Vol. 15, No. 4, 01.01.2014, p. 133-139.

Research output: Contribution to journalArticle

Grant, Philip ; Komarow, Lauren ; Sanchez, Alejandro ; Sattler, Fred ; Asmuth, David ; Pollard, Richard B ; Zolopa, Andrew. / Clinical and immunologic predictors of death after an acute opportunistic infection : Results from ACTG A5164. In: HIV Clinical Trials. 2014 ; Vol. 15, No. 4. pp. 133-139.
@article{52af97392bdd40e69da44e8efb59428d,
title = "Clinical and immunologic predictors of death after an acute opportunistic infection: Results from ACTG A5164",
abstract = "Background: In the pre-antiretroviral therapy (ART) era, markers of increased disease severity during an acute opportunistic infection (OI) were associated with mortality. Even with ART, mortality remains high during the first year after an OI in persons with advanced HIV infection, but it is unclear whether previous predictors of mortality remain valid in the current era. Objective: To determine clinical and immunological predictors of death after an OI. Methods: We used clinical data and stored plasma from ACTG A5164, a multicenter study evaluating the optimal timing of ART during a nontuberculous OI. We developed Cox models evaluating associations between clinical parameters and plasma marker levels at entry and time to death over the first 48 weeks after the diagnosis of OI. We developed multivariable models incorporating only clinical parameters, only plasma marker levels, or both. Results: The median CD4+ T-cell count in study participants at baseline was 29 cells/μL. Sixty-four percent of subjects had Pneumocystis jirovecii pneumonia (PCP). Twenty-three of 282 (8.2{\%}) subjects died. In univariate analyses, entry mycobacterial infection, OI number, hospitalization, low albumin, low hemoglobin, lower CD4, and higher IL-8 and sTNFrII levels and lower IL-17 levels were associated with mortality. In the combined model using both clinical and immunologic parameters, the presence of an entry mycobacterial infection and higher sTNFrII levels were significantly associated with death. Conclusions: In the ART era, clinical risk factors for death previously identified in the pre-ART era remain predictive. Additionally, activation of the innate immune system is associated with an increased risk of death following an acute OI.",
keywords = "HIV infections/complications, mortality, opportunistic infections",
author = "Philip Grant and Lauren Komarow and Alejandro Sanchez and Fred Sattler and David Asmuth and Pollard, {Richard B} and Andrew Zolopa",
year = "2014",
month = "1",
day = "1",
doi = "10.1310/hct1504-133",
language = "English (US)",
volume = "15",
pages = "133--139",
journal = "HIV Clinical Trials",
issn = "1528-4336",
publisher = "Thomas Land Publishers Inc.",
number = "4",

}

TY - JOUR

T1 - Clinical and immunologic predictors of death after an acute opportunistic infection

T2 - Results from ACTG A5164

AU - Grant, Philip

AU - Komarow, Lauren

AU - Sanchez, Alejandro

AU - Sattler, Fred

AU - Asmuth, David

AU - Pollard, Richard B

AU - Zolopa, Andrew

PY - 2014/1/1

Y1 - 2014/1/1

N2 - Background: In the pre-antiretroviral therapy (ART) era, markers of increased disease severity during an acute opportunistic infection (OI) were associated with mortality. Even with ART, mortality remains high during the first year after an OI in persons with advanced HIV infection, but it is unclear whether previous predictors of mortality remain valid in the current era. Objective: To determine clinical and immunological predictors of death after an OI. Methods: We used clinical data and stored plasma from ACTG A5164, a multicenter study evaluating the optimal timing of ART during a nontuberculous OI. We developed Cox models evaluating associations between clinical parameters and plasma marker levels at entry and time to death over the first 48 weeks after the diagnosis of OI. We developed multivariable models incorporating only clinical parameters, only plasma marker levels, or both. Results: The median CD4+ T-cell count in study participants at baseline was 29 cells/μL. Sixty-four percent of subjects had Pneumocystis jirovecii pneumonia (PCP). Twenty-three of 282 (8.2%) subjects died. In univariate analyses, entry mycobacterial infection, OI number, hospitalization, low albumin, low hemoglobin, lower CD4, and higher IL-8 and sTNFrII levels and lower IL-17 levels were associated with mortality. In the combined model using both clinical and immunologic parameters, the presence of an entry mycobacterial infection and higher sTNFrII levels were significantly associated with death. Conclusions: In the ART era, clinical risk factors for death previously identified in the pre-ART era remain predictive. Additionally, activation of the innate immune system is associated with an increased risk of death following an acute OI.

AB - Background: In the pre-antiretroviral therapy (ART) era, markers of increased disease severity during an acute opportunistic infection (OI) were associated with mortality. Even with ART, mortality remains high during the first year after an OI in persons with advanced HIV infection, but it is unclear whether previous predictors of mortality remain valid in the current era. Objective: To determine clinical and immunological predictors of death after an OI. Methods: We used clinical data and stored plasma from ACTG A5164, a multicenter study evaluating the optimal timing of ART during a nontuberculous OI. We developed Cox models evaluating associations between clinical parameters and plasma marker levels at entry and time to death over the first 48 weeks after the diagnosis of OI. We developed multivariable models incorporating only clinical parameters, only plasma marker levels, or both. Results: The median CD4+ T-cell count in study participants at baseline was 29 cells/μL. Sixty-four percent of subjects had Pneumocystis jirovecii pneumonia (PCP). Twenty-three of 282 (8.2%) subjects died. In univariate analyses, entry mycobacterial infection, OI number, hospitalization, low albumin, low hemoglobin, lower CD4, and higher IL-8 and sTNFrII levels and lower IL-17 levels were associated with mortality. In the combined model using both clinical and immunologic parameters, the presence of an entry mycobacterial infection and higher sTNFrII levels were significantly associated with death. Conclusions: In the ART era, clinical risk factors for death previously identified in the pre-ART era remain predictive. Additionally, activation of the innate immune system is associated with an increased risk of death following an acute OI.

KW - HIV infections/complications

KW - mortality

KW - opportunistic infections

UR - http://www.scopus.com/inward/record.url?scp=84906684880&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84906684880&partnerID=8YFLogxK

U2 - 10.1310/hct1504-133

DO - 10.1310/hct1504-133

M3 - Article

VL - 15

SP - 133

EP - 139

JO - HIV Clinical Trials

JF - HIV Clinical Trials

SN - 1528-4336

IS - 4

ER -