PMID- 31274541
OWN - NLM
STAT- MEDLINE
DCOM- 20200930
LR  - 20210110
IS  - 1473-5571 (Electronic)
IS  - 0269-9370 (Print)
IS  - 0269-9370 (Linking)
VI  - 33
IP  - 13
DP  - 2019 Nov 1
TI  - Inflammatory biomarkers prior to antiretroviral therapy as prognostic markers of 
      12-month mortality in South Africa and Uganda.
PG  - 2043-2048
LID - 10.1097/QAD.0000000000002305 [doi]
AB  - OBJECTIVE: The aim of this study was to determine the utility of biomarkers of 
      immune activation, systemic inflammation and coagulopathy prior to antiretroviral 
      therapy to predict mortality during the first year of antiretroviral therapy 
      (ART) in sub-Saharan Africa. DESIGN: A prospective, observational cohort. 
      METHODS: We measured soluble CD14, interleukin-6 and D-dimer in nonpregnant 
      individuals initiating ART in South Africa and Uganda in the Measuring Early 
      Treatment Adherence (META) Study. We used survival analysis methods to estimate 
      their association with 12-month mortality, and fit receiver operator curves (ROC) 
      to assess the prognostic value of each biomarker. RESULTS: Six-hundred and sixty 
      individuals were enrolled and had pretreatment biomarkers measured. Approximately 
      60% were women, with a median CD4 cell count of 187 cells/mul [interquartile range 
      (IQR) 111-425] and approximately half were enrolled each from South Africa and 
      Uganda. We observed 34 deaths for a crude mortality of 5.3 deaths/100 
      person-years (py) (95% confidence interval 3.8-7.4), which ranged from 0/100 py 
      to 13.7/100 py in the lowest and highest tertile of pretreatment sCD14, 
      respectively. In Cox models, all three biomarkers were strongly predictive of the 
      hazard of death (adjusted hazard ratio 3-6, all P < 0.01). In multivariable 
      models including biomarkers, both pretreatment CD4 cell count and pretreatment 
      viral load became borderline or nonsignificantly associated with mortality. The 
      c-statistic for area under ROC was higher for all three biomarkers than for CD4 
      cell count (P < 0.01). CONCLUSION: Biomarkers of immune activation, systemic 
      inflammation and coagulopathy prior to ART initiation are strongly predictive of 
      early death on treatment after adjustment for CD4 cell count. Such biomarkers 
      might serve as important prognostic indicators for patient triage in this 
      population.
FAU - Siedner, Mark J
AU  - Siedner MJ
AD  - aHarvard Medical School bMassachusetts General Hospital, Boston, Massachusetts, 
      USA cMbarara University of Science and Technology, Mbarara, Uganda dAfrica Health 
      Research Institute, Kwa-Zulu Natal, South Africa eUniversity of Colorado, Denver, 
      Colorado fUniversity of Vermont, Burlington, Vermont gOregon Health Sciences 
      University-Portland State University School of Public Health, Portland, Oregon, 
      USA hUniversity of Cape Town, Cape Town, South Africa.
FAU - Bwana, Mwebesa Bosco
AU  - Bwana MB
FAU - Asiimwe, Stephen
AU  - Asiimwe S
FAU - Musinguzi, Nicholas
AU  - Musinguzi N
FAU - Castillo-Mancilla, Jose
AU  - Castillo-Mancilla J
FAU - Amanyire, Gideon
AU  - Amanyire G
FAU - Tracy, Russell P
AU  - Tracy RP
FAU - Bangsberg, David R
AU  - Bangsberg DR
FAU - Orrell, Catherine
AU  - Orrell C
FAU - Haberer, Jessica E
AU  - Haberer JE
CN  - META Study Investigators
LA  - eng
GR  - K23 MH099916/MH/NIMH NIH HHS/United States
GR  - P20 GM125498/GM/NIGMS NIH HHS/United States
GR  - R01 HL141053/HL/NHLBI NIH HHS/United States
GR  - P30 AI060354/AI/NIAID NIH HHS/United States
PT  - Journal Article
PT  - Observational Study
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - AIDS
JT  - AIDS (London, England)
JID - 8710219
RN  - 0 (Anti-HIV Agents)
RN  - 0 (Biomarkers)
RN  - 0 (Fibrin Fibrinogen Degradation Products)
RN  - 0 (IL6 protein, human)
RN  - 0 (Interleukin-6)
RN  - 0 (Lipopolysaccharide Receptors)
RN  - 0 (fibrin fragment D)
SB  - IM
MH  - Adult
MH  - Anti-HIV Agents/*therapeutic use
MH  - Biomarkers/*blood
MH  - Female
MH  - Fibrin Fibrinogen Degradation Products/analysis
MH  - HIV Infections/blood/*drug therapy/*mortality
MH  - Humans
MH  - Interleukin-6/blood
MH  - Lipopolysaccharide Receptors/blood
MH  - Male
MH  - Prognosis
MH  - Prospective Studies
MH  - ROC Curve
MH  - South Africa/epidemiology
MH  - Survival Analysis
MH  - Time Factors
MH  - Uganda/epidemiology
MH  - Viral Load
PMC - PMC6774817
MID - NIHMS1534354
EDAT- 2019/07/06 06:00
MHDA- 2020/10/02 06:00
PMCR- 2019/10/14
CRDT- 2019/07/06 06:00
PHST- 2019/07/06 06:00 [pubmed]
PHST- 2020/10/02 06:00 [medline]
PHST- 2019/07/06 06:00 [entrez]
PHST- 2019/10/14 00:00 [pmc-release]
AID - AIDS-D-19-00332 [pii]
AID - 10.1097/QAD.0000000000002305 [doi]
PST - ppublish
SO  - AIDS. 2019 Nov 1;33(13):2043-2048. doi: 10.1097/QAD.0000000000002305.