Effect of maraviroc intensification on HIV-1-specific T cell immunity in recently HIV-1-infected individuals.
BACKGROUND
The effect of maraviroc on the maintenance and the function of HIV-1-specific T cell responses remains unknown.


METHODS
Subjects recently infected with HIV-1 were randomized to receive anti-retroviral treatment with or without maraviroc intensification for 48 weeks, and were monitored up to week 60. PBMC and in vitro-expanded T cells were tested for responses to the entire HIV proteome by ELISpot analyses. Intracellular cytokine staining assays were conducted to monitor the (poly)-functionality of HIV-1-specific T cells. Analyses were performed at baseline and week 24 after treatment start, and at week 60 (3 months after maraviroc discontinuation).


RESULTS
Maraviroc intensification was associated with a slower decay of virus-specific T cell responses over time compared to the non-intensified regimen in both direct ex-vivo as well as in in-vitro expanded cells. The effector function profiles of virus-specific CD8⁺ T cells were indistinguishable between the two arms and did not change over time between the groups.


CONCLUSIONS
Maraviroc did not negatively impact any of the measured parameters, but was rather associated with a prolonged maintenance of HIV-1-specific T cell responses. Maraviroc, in addition to its original effect as viral entry inhibitor, may provide an additional benefit on the maintenance of virus-specific T cells which may be especially important for future viral eradication strategies.
Irsicaixa AIDS Research Institute - HIVACAT, Autonomous University of Barcelona, Badalona, Spain ; Division of Infectious Diseases, Advanced Clinical Research Center, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan.
Ai
A
Kawana-Tachikawa
Lluita contra la SIDA Foundation, HIV Unit, University Hospital Germans Trias i Pujol, Badalona, UAB, Badalona, Spain.
Josep M
JM
Llibre
Lluita contra la SIDA Foundation, HIV Unit, University Hospital Germans Trias i Pujol, Badalona, UAB, Badalona, Spain.
Isabel
I
Bravo
Lluita contra la SIDA Foundation, HIV Unit, University Hospital Germans Trias i Pujol, Badalona, UAB, Badalona, Spain.
Roser
R
Escrig
Irsicaixa AIDS Research Institute - HIVACAT, Autonomous University of Barcelona, Badalona, Spain ; Lluita contra la SIDA Foundation, HIV Unit, University Hospital Germans Trias i Pujol, Badalona, UAB, Badalona, Spain ; University of Vic, Vic, Spain.
Beatriz
B
Mothe
Lluita contra la SIDA Foundation, HIV Unit, University Hospital Germans Trias i Pujol, Badalona, UAB, Badalona, Spain.
Jordi
J
Puig
Irsicaixa AIDS Research Institute - HIVACAT, Autonomous University of Barcelona, Badalona, Spain.
Maria C
MC
Puertas
Irsicaixa AIDS Research Institute - HIVACAT, Autonomous University of Barcelona, Badalona, Spain ; University of Vic, Vic, Spain ; Institució Catalana de Recerca i Estudis Avancats (ICREA), Barcelona, Spain.
Javier
J
Martinez-Picado
Irsicaixa AIDS Research Institute - HIVACAT, Autonomous University of Barcelona, Badalona, Spain ; University of Vic, Vic, Spain.
Julia
J
Blanco
Hospital Clínic-IDIBAPS, University of Barcelona, Barcelona, Spain.
Christian
C
Manzardo
Hospital Clínic-IDIBAPS, University of Barcelona, Barcelona, Spain.
Jose M
JM
Miro
Division of Infectious Diseases, Advanced Clinical Research Center, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan.
Aikichi
A
Iwamoto
HIV/GUM Department, Chelsea and Westminster Hospital, London, United Kingdom.
Anton L
AL
Pozniak
Hospital Clínic-IDIBAPS, University of Barcelona, Barcelona, Spain.
Jose M
JM
Gatell
Irsicaixa AIDS Research Institute - HIVACAT, Autonomous University of Barcelona, Badalona, Spain ; Lluita contra la SIDA Foundation, HIV Unit, University Hospital Germans Trias i Pujol, Badalona, UAB, Badalona, Spain ; University of Vic, Vic, Spain.
Bonaventura
B
Clotet
Irsicaixa AIDS Research Institute - HIVACAT, Autonomous University of Barcelona, Badalona, Spain ; University of Vic, Vic, Spain ; Institució Catalana de Recerca i Estudis Avancats (ICREA), Barcelona, Spain.
Christian
C
Brander
D044966:Anti-Retroviral Agents / Q000494:pharmacology*; D003510:Cyclohexanes / Q000494:pharmacology*; D016207:Cytokines / Q000032:analysis; D058501:Enzyme-Linked Immunospot Assay; D005434:Flow Cytometry; D015658:HIV Infections / Q000276:immunology*; D015497:HIV-1; D006801:Humans; D007111:Immunity, Cellular / Q000187:drug effects*; D000077592:Maraviroc; D019713:Receptors, CCR5 / Q000378:metabolism; D018709:Statistics, Nonparametric; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology*; D014230:Triazoles / Q000494:pharmacology*; D053586:Virus Internalization / Q000187:drug effects
D044966:Anti-Retroviral Agents; D003510:Cyclohexanes; D016207:Cytokines; D019713:Receptors, CCR5; D014230:Triazoles; D000077592:Maraviroc