PMID- 22875102
OWN - NLM
STAT- MEDLINE
DCOM- 20130509
LR  - 20211021
IS  - 1528-3658 (Electronic)
IS  - 1076-1551 (Print)
IS  - 1076-1551 (Linking)
VI  - 18
IP  - 1
DP  - 2012 Oct 24
TI  - CCR5 antagonism impacts vaccination response and immune profile in HIV-1 
      infection.
PG  - 1240-8
LID - 10.2119/molmed.2012.00206 [doi]
AB  - Maraviroc (MVC) is the first licensed antiretroviral therapeutic agent to target 
      a host cell surface molecule, and successful HIV-1 entry blockade by this C-C 
      chemokine receptor type 5 (CCR5)-antagonist potentiates immunomodulation. We 
      hypothesized that MVC intensification impacts immunization responses, T-cell 
      phenotype, function and delayed type hypersensitivity (DTH) in HIV-1(+) subjects. 
      A 24-wk, double-blinded, placebo-controlled study of the addition of MVC to 
      suppressive antiretroviral therapy in HIV-1(+) persons was performed. Subjects 
      received DTH tests, intramuscular tetanus, meningococcal and oral cholera 
      immunizations. Antibody titers, T-cell function and phenotype were assessed. Of 
      157 patients referred, 47 were randomized 1:1; MVC:placebo. MVC enhanced 
      meningococcal neo-immunization, blunted cholera response and expedited 
      lymphoproliferation to tetanus boost, without affecting recall humoral response. 
      Anti-HIV-1 group-specific antigen (Gag) and tetanus toxoid (TTox) function 
      improved significantly, HIV-1-associated CD8 T-cell skewing normalized, and the 
      percentage of late-stage and major histocompatibility complex (MHC) class II 
      expressing CD4 T-cells increased. Activated CD4(+) CD38(+) human leukocyte 
      antigen (HLA)-DR(+) T-cells declined, and costimulation shifted to coinhibition. 
      DTH was unchanged. Maraviroc intensification, through antagonism of the cell 
      surface molecule CCR5, favorably influences immune profiles of HIV-1(+) patients, 
      supporting its immunomodulatory use in HIV-1 infection and potentially in other 
      immunologically relevant settings.
FAU - Westrop, Samantha J
AU  - Westrop SJ
AD  - Department of Medicine, Imperial College London, London, UK.
FAU - Moyle, Graeme
AU  - Moyle G
FAU - Jackson, Akil
AU  - Jackson A
FAU - Nelson, Mark
AU  - Nelson M
FAU - Mandalia, Sundhiya
AU  - Mandalia S
FAU - Imami, Nesrina
AU  - Imami N
LA  - eng
GR  - G0501957/Medical Research Council/United Kingdom
PT  - Clinical Trial, Phase IV
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20121024
PL  - England
TA  - Mol Med
JT  - Molecular medicine (Cambridge, Mass.)
JID - 9501023
RN  - 0 (AIDS Vaccines)
RN  - 0 (CCR5 Receptor Antagonists)
RN  - 0 (Cyclohexanes)
RN  - 0 (Receptors, CCR5)
RN  - 0 (Triazoles)
RN  - MD6P741W8A (Maraviroc)
SB  - IM
MH  - AIDS Vaccines/*immunology
MH  - *CCR5 Receptor Antagonists
MH  - Cyclohexanes/adverse effects/pharmacology
MH  - Female
MH  - HIV Infections/*immunology/*prevention & control
MH  - HIV-1/drug effects/*immunology
MH  - Humans
MH  - Immunity/drug effects/*immunology
MH  - Immunity, Cellular/drug effects/immunology
MH  - Immunity, Humoral/drug effects/immunology
MH  - Immunophenotyping
MH  - Male
MH  - Maraviroc
MH  - Middle Aged
MH  - Receptors, CCR5/metabolism
MH  - T-Lymphocytes/drug effects/immunology
MH  - Treatment Outcome
MH  - Triazoles/adverse effects/pharmacology
MH  - *Vaccination/adverse effects
PMC - PMC3510292
EDAT- 2012/08/10 06:00
MHDA- 2013/05/10 06:00
PMCR- 2012/08/07
CRDT- 2012/08/10 06:00
PHST- 2012/05/08 00:00 [received]
PHST- 2012/08/07 00:00 [accepted]
PHST- 2012/08/10 06:00 [entrez]
PHST- 2012/08/10 06:00 [pubmed]
PHST- 2013/05/10 06:00 [medline]
PHST- 2012/08/07 00:00 [pmc-release]
AID - molmed.2012.00206 [pii]
AID - 12_206_westrop [pii]
AID - 10.2119/molmed.2012.00206 [doi]
PST - epublish
SO  - Mol Med. 2012 Oct 24;18(1):1240-8. doi: 10.2119/molmed.2012.00206.