PMID- 21592994
OWN - NLM
STAT- MEDLINE
DCOM- 20110808
LR  - 20220408
IS  - 1537-6613 (Electronic)
IS  - 0022-1899 (Print)
IS  - 0022-1899 (Linking)
VI  - 203
IP  - 11
DP  - 2011 Jun 1
TI  - Higher levels of CRP, D-dimer, IL-6, and hyaluronic acid before initiation of 
      antiretroviral therapy (ART) are associated with increased risk of AIDS or death.
PG  - 1637-46
LID - 10.1093/infdis/jir134 [doi]
AB  - BACKGROUND: Substantial morbidity occurs during the first year of antiretroviral 
      therapy (ART) in persons with advanced human immunodeficiency virus (HIV) disease 
      despite HIV suppression. Biomarkers may identify high-risk groups. METHODS: 
      Pre-ART and 1-month samples from an initial ART trial were evaluated for 
      biomarkers associated with AIDS events or death within 1-12 months. Case patients 
      (n = 63) and control patients (n = 126) were 1:2 matched on baseline CD4 cell 
      count, hepatitis status, and randomization date. All had >/= 1 log(10) HIV RNA 
      level decrease at 1 month. RESULTS: Case patients had more frequent prior AIDS 
      events, compared with control patients (P = .004), but similar HIV RNA levels at 
      baseline. Pre-ART and 1-month C-reactive protein (CRP), D-dimer, and interleukin 
      6 (IL-6) levels and pre-ART hyaluronic acid (HA) levels were associated with new 
      AIDS events or death (P </= .01). Patients who experienced immune reconstitution 
      inflammatory syndrome (IRIS) events had higher pre-ART tumor necrosis factor alpha 
      (TNF-alpha) and HIV RNA levels and significant 1-month increases in CRP, D-dimer, 
      IL-6, interleukin 8, CXCL10, TNF-alpha, and interferon-gamma levels, compared with 
      patients who experienced non-IRIS events (P </= .03). Individuals with baseline CRP 
      and HA levels above the cohort median (>2.1 mg/L and >50.0 ng/mL, respectively) 
      had increased risk of AIDS or death (OR, 4.6 [95% CI, 2.0-10.3]; P < .001) and 
      IRIS (OR, 8.7 [95% CI, 2.2-34.8] P = .002). CONCLUSIONS: Biomarkers of 
      Inflammation (CRP, IL-6), coagulation (D-dimer), and tissue fibrosis (HA) 
      measured pre-ART and at 1 month are associated with higher risk of AIDS events, 
      IRIS, or death, warranting additional study as risk stratification strategies.
FAU - Boulware, David R
AU  - Boulware DR
AD  - University of Minnesota, Minneapolis, Minnesota, USA.
FAU - Hullsiek, Katherine Huppler
AU  - Hullsiek KH
FAU - Puronen, Camille E
AU  - Puronen CE
FAU - Rupert, Adam
AU  - Rupert A
FAU - Baker, Jason V
AU  - Baker JV
FAU - French, Martyn A
AU  - French MA
FAU - Bohjanen, Paul R
AU  - Bohjanen PR
FAU - Novak, Richard M
AU  - Novak RM
FAU - Neaton, James D
AU  - Neaton JD
FAU - Sereti, Irini
AU  - Sereti I
CN  - INSIGHT Study Group
LA  - eng
GR  - U01AI042170/AI/NIAID NIH HHS/United States
GR  - L30 AI066779/AI/NIAID NIH HHS/United States
GR  - K23AI073192-02/AI/NIAID NIH HHS/United States
GR  - K24 AI096925/AI/NIAID NIH HHS/United States
GR  - U01AI046362/AI/NIAID NIH HHS/United States
GR  - MC_U122886352/MRC_/Medical Research Council/United Kingdom
GR  - K12RR023247-05/RR/NCRR NIH HHS/United States
GR  - K23 AI073192/AI/NIAID NIH HHS/United States
GR  - U01AI068641/AI/NIAID NIH HHS/United States
GR  - K23 AI073192-03/AI/NIAID NIH HHS/United States
GR  - L30 AI066779-05/AI/NIAID NIH HHS/United States
GR  - KL2 RR033182/RR/NCRR NIH HHS/United States
PT  - Journal Article
PT  - Randomized Controlled Trial
PT  - Research Support, N.I.H., Extramural
PL  - United States
TA  - J Infect Dis
JT  - The Journal of infectious diseases
JID - 0413675
RN  - 0 (Anti-Retroviral Agents)
RN  - 0 (Biomarkers)
RN  - 0 (Fibrin Fibrinogen Degradation Products)
RN  - 0 (IL6 protein, human)
RN  - 0 (Interleukin-6)
RN  - 0 (RNA, Viral)
RN  - 0 (fibrin fragment D)
RN  - 9004-61-9 (Hyaluronic Acid)
RN  - 9007-41-4 (C-Reactive Protein)
SB  - IM
MH  - Acquired Immunodeficiency Syndrome/*blood/drug therapy
MH  - Adult
MH  - Anti-Retroviral Agents/therapeutic use
MH  - Biomarkers/blood/metabolism
MH  - C-Reactive Protein/*metabolism
MH  - Case-Control Studies
MH  - Disease Progression
MH  - Female
MH  - Fibrin Fibrinogen Degradation Products/*metabolism
MH  - HIV Infections/*blood/*drug therapy
MH  - Humans
MH  - Hyaluronic Acid/*blood
MH  - Immune Reconstitution Inflammatory Syndrome/blood/virology
MH  - Interleukin-6/*blood
MH  - Male
MH  - Middle Aged
MH  - Morbidity
MH  - RNA, Viral/blood
MH  - Risk Factors
PMC - PMC3096784
EDAT- 2011/05/20 06:00
MHDA- 2011/08/09 06:00
PMCR- 2012/06/01
CRDT- 2011/05/20 06:00
PHST- 2011/05/20 06:00 [entrez]
PHST- 2011/05/20 06:00 [pubmed]
PHST- 2011/08/09 06:00 [medline]
PHST- 2012/06/01 00:00 [pmc-release]
AID - jir134 [pii]
AID - 10.1093/infdis/jir134 [doi]
PST - ppublish
SO  - J Infect Dis. 2011 Jun 1;203(11):1637-46. doi: 10.1093/infdis/jir134.