Clinical and immunologic predictors of death after an acute opportunistic infection: results from ACTG A5164.

TitleClinical and immunologic predictors of death after an acute opportunistic infection: results from ACTG A5164.
Publication TypeJournal Article
Year of Publication2014
AuthorsGrant PM, Komarow L, Sanchez A, Sattler FR, Asmuth DM, Pollard RB, Zolopa AR
JournalHIV Clin Trials
Volume15
Issue4
Pagination133-9
Date Published2014 Jul-Aug
ISSN1528-4336
KeywordsAcquired Immunodeficiency Syndrome, Adult, AIDS-Related Opportunistic Infections, Female, Humans, Male, Multivariate Analysis, Proportional Hazards Models, Risk Factors
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.

DOI10.1310/hct1504-133
Alternate JournalHIV Clin Trials
PubMed ID25143022
PubMed Central IDPMC4167015
Grant ListK23 AI108358 / AI / NIAID NIH HHS / United States
K23AI108358 / AI / NIAID NIH HHS / United States
U01 AI068634 / AI / NIAID NIH HHS / United States
U01AI068634 / AI / NIAID NIH HHS / United States
UL1 TR000439 / TR / NCATS NIH HHS / United States
UM1 AI068634 / AI / NIAID NIH HHS / United States
UM1 AI068636 / AI / NIAID NIH HHS / United States
UM1 AI069428 / AI / NIAID NIH HHS / United States
UM1 AI069432 / AI / NIAID NIH HHS / United States
UM1 AI069556 / AI / NIAID NIH HHS / United States
UM1 AI106701 / AI / NIAID NIH HHS / United States
UM1AI068634 / AI / NIAID NIH HHS / United States
UM1AI068636 / AI / NIAID NIH HHS / United States
UM1AI069428 / AI / NIAID NIH HHS / United States
UM1AI069556 / AI / NIAID NIH HHS / United States