PMID- 22363790
OWN - NLM
STAT- MEDLINE
DCOM- 20120629
LR  - 20211021
IS  - 1932-6203 (Electronic)
IS  - 1932-6203 (Linking)
VI  - 7
IP  - 2
DP  - 2012
TI  - Circulating sCD14 is associated with virological response to 
      pegylated-interferon-alpha/ribavirin treatment in HIV/HCV co-infected patients.
PG  - e32028
LID - 10.1371/journal.pone.0032028 [doi]
LID - e32028
AB  - OBJECTIVES: Microbial translocation (MT) through the gut accounts for immune 
      activation and CD4+ loss in HIV and may influence HCV disease progression in 
      HIV/HCV co-infection. We asked whether increased MT and immune activation may 
      hamper anti-HCV response in HIV/HCV patients. METHODS: 98 HIV/HCV patients who 
      received pegylated-alpha-interferon (peg-INF-alpha)/ribavirin were 
      retrospectively analyzed. Baseline MT (lipopolysaccharide, LPS), host response to 
      MT (sCD14), CD38+HLA-DR+CD4+/CD8+, HCV genotype, severity of liver disease were 
      assessed according to Early Virological Response (EVR: HCV-RNA <50 IU/mL at week 
      12 of therapy or >/=2 log(10) reduction from baseline after 12 weeks of therapy) 
      and Sustained Virological Response (SVR: HCV-RNA <50 IU/mL 24 weeks after end of 
      therapy). Mann-Whitney/Chi-square test and Pearson's correlation were used. 
      Multivariable regression was performed to determine factors associated with 
      EVR/SVR. RESULTS: 71 patients displayed EVR; 41 SVR. Patients with HCV genotypes 
      1-4 and cirrhosis presented a trend to higher sCD14, compared to patients with 
      genotypes 2-3 (p = 0.053) and no cirrhosis (p = 0.052). EVR and SVR patients 
      showed lower levels of circulating sCD14 (p = 0.0001, p = 0.026, respectively), 
      but similar T-cell activation compared to Non-EVR (Null Responders, NR) and 
      Non-SVR (N-SVR) subjects. sCD14 resulted the main predictive factor of EVR (0.145 
      for each sCD14 unit more, 95%CI 0.031-0.688, p = 0.015). SVR was associated only 
      with HCV genotypes 2-3 (AOR 0.022 for genotypes 1-4 vs 2-3, 95%CI 0.001-0.469, 
      p = 0.014). CONCLUSIONS: In HIV/HCV patients sCD14 correlates with the severity 
      of liver disease and predicts early response to peg-INF-alpha/ribavirin, 
      suggesting MT-driven immune activation as pathway of HIV/HCV co-infection and 
      response to therapy.
FAU - Marchetti, Giulia
AU  - Marchetti G
AD  - Department of Medicine, Surgery and Dentistry, Clinic of Infectious Diseases and 
      Tropical Medicine, University of Milan, San Paolo Hospital, Milan, Italy. 
      giulia.marchetti@unimi.it
FAU - Nasta, Paola
AU  - Nasta P
FAU - Bai, Francesca
AU  - Bai F
FAU - Gatti, Francesca
AU  - Gatti F
FAU - Bellistri, Giusi Maria
AU  - Bellistri GM
FAU - Tincati, Camilla
AU  - Tincati C
FAU - Borghi, Federica
AU  - Borghi F
FAU - Carosi, Giampiero
AU  - Carosi G
FAU - Puoti, Massimo
AU  - Puoti M
FAU - Monforte, Antonella d'Arminio
AU  - Monforte Ad
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20120221
PL  - United States
TA  - PLoS One
JT  - PloS one
JID - 101285081
RN  - 0 (Biomarkers)
RN  - 0 (HLA-DR Antigens)
RN  - 0 (Interferon-alpha)
RN  - 0 (Lipopolysaccharide Receptors)
RN  - 0 (Lipopolysaccharides)
RN  - 0 (Recombinant Proteins)
RN  - 3WJQ0SDW1A (Polyethylene Glycols)
RN  - 49717AWG6K (Ribavirin)
RN  - Q46947FE7K (peginterferon alfa-2a)
SB  - IM
MH  - Adult
MH  - Bacteria/drug effects
MH  - Biomarkers/metabolism
MH  - CD4-Positive T-Lymphocytes/drug effects/immunology
MH  - CD8-Positive T-Lymphocytes/drug effects/immunology
MH  - Coinfection/complications/drug therapy/immunology/virology
MH  - Demography
MH  - Female
MH  - Fibrosis/complications/microbiology/virology
MH  - HIV Infections/blood/*complications/*drug therapy/virology
MH  - HLA-DR Antigens/immunology
MH  - Hepatitis C, Chronic/complications/*drug therapy/immunology/*virology
MH  - Humans
MH  - Interferon-alpha/pharmacology/*therapeutic use
MH  - Lipopolysaccharide Receptors/*blood
MH  - Lipopolysaccharides/blood
MH  - Lymphocyte Activation/drug effects/immunology
MH  - Male
MH  - Middle Aged
MH  - Polyethylene Glycols/pharmacology/*therapeutic use
MH  - Recombinant Proteins/pharmacology/therapeutic use
MH  - Ribavirin/pharmacology/*therapeutic use
MH  - Solubility/drug effects
MH  - Treatment Outcome
PMC - PMC3283684
COIS- Competing Interests: The authors have declared that no competing interests exist.
EDAT- 2012/03/01 06:00
MHDA- 2012/06/30 06:00
PMCR- 2012/02/21
CRDT- 2012/02/25 06:00
PHST- 2011/12/01 00:00 [received]
PHST- 2012/01/17 00:00 [accepted]
PHST- 2012/02/25 06:00 [entrez]
PHST- 2012/03/01 06:00 [pubmed]
PHST- 2012/06/30 06:00 [medline]
PHST- 2012/02/21 00:00 [pmc-release]
AID - PONE-D-11-24207 [pii]
AID - 10.1371/journal.pone.0032028 [doi]
PST - ppublish
SO  - PLoS One. 2012;7(2):e32028. doi: 10.1371/journal.pone.0032028. Epub 2012 Feb 21.