PMID- 16181494
OWN - NLM
STAT- PubMed-not-MEDLINE
DCOM- 20051026
LR  - 20220129
IS  - 1476-8518 (Electronic)
IS  - 1476-8518 (Linking)
VI  - 3
DP  - 2005 Sep 25
TI  - Mycobacterial immune reconstitution inflammatory syndrome in HIV-1 infection 
      after antiretroviral therapy is associated with deregulated specific T-cell 
      responses: beneficial effect of IL-2 and GM-CSF immunotherapy.
PG  - 7
AB  - BACKGROUND: With the advent of antiretroviral therapy (ART) cases of immune 
      reconstitution inflammatory syndrome (IRIS) have increasingly been reported. IRIS 
      usually occurs in individuals with a rapidly rising CD4 T-cell count or 
      percentage upon initiation of ART, who develop a deregulated immune response to 
      infection with or without reactivation of opportunistic organisms. Here, we 
      evaluated rises in absolute CD4 T-cells, and specific CD4 T-cell responses in 4 
      HIV-1+ individuals presenting with mycobacterial associated IRIS who received in 
      conjunction with ART, IL-2 plus GM-CSF immunotherapy. METHODS: We assessed CD4 
      T-cell counts, HIV-1 RNA loads, phenotype for naive and activation markers, and 
      in vitro proliferative responses. Results were compared with those observed in 11 
      matched, successfully treated asymptomatic clinical progressors (CP) with no 
      evidence of opportunistic infections, and uninfected controls. RESULTS: Median 
      CD4 T-cell counts in IRIS patients rose from 22 cells/microl before initiation of 
      ART, to 70 cells/microl after 8 months of therapy (median 6.5 fold increase). 
      This coincided with IRIS diagnosis, lower levels of naive CD4 T-cells, increased 
      expression of immune activation markers, and weak CD4 T-cell responses. In 
      contrast, CP had a median CD4 T-cell counts of 76 cells/microl at baseline, which 
      rose to 249 cells/microl 6 months post ART, when strong T-cell responses were 
      seen in > 80% of patients. Higher levels of expression of immune activation 
      markers were seen in IRIS patients compared to CP and UC (IRIS > CP > UC). 
      Immunotherapy with IL-2 and GM-CSF paralleled clinical recovery. CONCLUSION: 
      These data suggest that mycobacterial IRIS is associated with inadequate immune 
      reconstitution rather than vigorous specific T-cell responses, and concomitant 
      administration of IL-2 and GM-CSF immunotherapy with effective ART may 
      correct/augment T-cell immunity in such setting resulting in clinical benefit.
FAU - Pires, A
AU  - Pires A
AD  - Department of Immunology, Imperial College London, Chelsea and Westminster 
      Hospital, London, UK. antonio.pires@meditechmedia.com
FAU - Nelson, M
AU  - Nelson M
FAU - Pozniak, A L
AU  - Pozniak AL
FAU - Fisher, M
AU  - Fisher M
FAU - Gazzard, B
AU  - Gazzard B
FAU - Gotch, F
AU  - Gotch F
FAU - Imami, N
AU  - Imami N
LA  - eng
GR  - G0501957/MRC_/Medical Research Council/United Kingdom
PT  - Journal Article
DEP - 20050925
PL  - England
TA  - J Immune Based Ther Vaccines
JT  - Journal of immune based therapies and vaccines
JID - 101152206
PMC - PMC1262752
EDAT- 2005/09/27 09:00
MHDA- 2005/09/27 09:01
PMCR- 2005/09/25
CRDT- 2005/09/27 09:00
PHST- 2004/04/06 00:00 [received]
PHST- 2005/09/25 00:00 [accepted]
PHST- 2005/09/27 09:00 [pubmed]
PHST- 2005/09/27 09:01 [medline]
PHST- 2005/09/27 09:00 [entrez]
PHST- 2005/09/25 00:00 [pmc-release]
AID - 1476-8518-3-7 [pii]
AID - 10.1186/1476-8518-3-7 [doi]
PST - epublish
SO  - J Immune Based Ther Vaccines. 2005 Sep 25;3:7. doi: 10.1186/1476-8518-3-7.