Maraviroc intensification for HIV-1-positive immunological non-responders (INRs) despite virological suppression during HAART

  • S Rusconi
  • P Vitiello
  • F Adorni
  • E Colella
  • E Focà
  • AF Capetti
  • P Meraviglia
  • C Abeli
  • S Bonora
  • M D'Annunzio
  • A Di Biagio
  • A Di Pietro
  • L Butini
  • G Orofino
  • S Farina
  • G d'Ettorre
  • D Francisci
  • A Soria
  • AR Buonomini
  • C Tommasi
  • MP Trotta
  • M Capasso
  • E Merlini
  • GC Marchetti
Open Access
Oral presentation
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Keywords

Maraviroc Virologic Suppression Memory Pool Immunological Recovery Parallel Rise 

Purpose

15-30% of HAART-treated HIV-1-positive patients (pts) lack CD4+ increase despite full HIV viremia suppression. The increased risk for INR to progress till AIDS led us to investigate maraviroc (MVC) as a tool to intensify HAART in terms of immunological recovery.

Methods

Randomised, multicentre, proof-of-concept study enrolling 100 pts divided into 2 arms (1:1), A:HAART+MVC, B:HAART. Inclusion criteria were: CD4 count ≥200 cells/µL and/or a recovery of CD4 cells <25% compared to the HAART initiation and with a stable virologic suppression after 1 year of HAART. Ultrasensitive HIV-RNA was quantified via Amplicor HIV-1 Monitor Kit v1.5. Naive CD45RA+, memory CD45RA-, activated HLA-DR+CD38+, proliferating Ki67+, CD4+, CD8+ T-cells were measured by flow cytometry. T-test was used for intra and inter-group comparisons.

Results

100 pts have been randomized 64 pts reached week(w) 12: 37 in A and 27 in B arms. At baseline (BL), CD4/CD8 and immune-phenotype were comparable in arm A and B. At w12 no significant changes in mean CD4 recovery (+41.9 vs +24.5/µL; p=.241) and a statistically significant change in mean CD8+ count (+164.2 vs -27.3/µL; p=.004) were observed between pts in arm A and B.

At BL and w12 an immunological study was carried out in 24 pts (13:arm A, 11:arm B): at w12, while B pts experienced a contraction of naïve CD4 (81 to 67%; p=.02) and CD8 (81 to 77%; p=.04) with a parallel rise in memory CD4 (16 to 30%; p=.02) and CD8 (13 to 17%; p=.06), no significant loss of naive CD4 (70 to 57%; p=.18) and CD8 (69 to 66%; p=.42) was displayed by A pts with a tendency to higher gain in memory CD4 (24 to 40%; p=.06) and CD8 (11 to 25%; p=.008). By w12, a similar reduction in activated HLA-DR+CD38+ CD8 and CD4 was shown in B (p=.05) and A pts (p=.03 and p=.02 for CD8 and CD4). A trend to Ki67+CD8 reduction was shown in A (p=.06) and not in B pts (p=.45). HIV-RNA quantification evidenced a trend to higher median values (BL vs w12) in B pts: 2 vs 5 cp/mL (p=.37).

Conclusions

MVC does not seem to increase CD4 amount at significant level compared to arm B. Treatment with MVC is associated with a significant CD8+ gain, a preservation of phenotypically naïve CD4+ and parallel rise of memory pool, suggesting a role of MVC in reducing peripheral antigen-driven T-cell death, possibly preserving new T-cell production. MVC is able to further reduce T-cell activation and proliferation, suggesting a possible influence in better controlling the pro-inflammatory status.

We acknowledge the participation of all investigators of the HSL/MVC01/2008 Study Group (NCT00884858).

Copyright information

© Rusconi et al; licensee BioMed Central Ltd. 2010

This article is published under license to BioMed Central Ltd. This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Authors and Affiliations

  • S Rusconi
    • 1
  • P Vitiello
    • 1
  • F Adorni
    • 2
  • E Colella
    • 1
  • E Focà
    • 3
  • AF Capetti
    • 4
  • P Meraviglia
    • 5
  • C Abeli
    • 6
  • S Bonora
    • 7
  • M D'Annunzio
    • 8
  • A Di Biagio
    • 9
  • A Di Pietro
    • 10
  • L Butini
    • 11
  • G Orofino
    • 12
  • S Farina
    • 13
  • G d'Ettorre
    • 14
  • D Francisci
    • 15
  • A Soria
    • 16
  • AR Buonomini
    • 17
  • C Tommasi
    • 18
  • MP Trotta
    • 19
  • M Capasso
    • 1
  • E Merlini
    • 20
  • GC Marchetti
    • 20
  1. 1.Dipartimento di Scienze Cliniche “Luigi Sacco”, Sezione di Malattie Infettive-ImmunopatologiaUniversità degli Studi di MilanoMilanoItaly
  2. 2.ITB-CNRSegrateItaly
  3. 3.Clinica Malattie Infettive, Università degli Studi di BresciaSpedali CiviliBresciaItaly
  4. 4.1a Div. Malattie InfettiveOspedale Luigi SaccoMilanoItaly
  5. 5.2a Div. Malattie InfettiveOspedale Luigi SaccoMilanoItaly
  6. 6.Div. Malattie InfettiveOspedale di CircoloBusto ArsizioItaly
  7. 7.Clinica Malattie InfettiveUniversità degli Studi di TorinoTorinoItaly
  8. 8.Clinica di Malattie InfettiveOspedale Policlinico di BariBariItaly
  9. 9.Clinica Malattie Infettive, Università degli Studi di GenovaOspedale San MartinoGenovaItaly
  10. 10.Div. Malattie InfettiveOspedale S. Maria AnnunziataAntellaItaly
  11. 11.Servizio Regionale di Immunologia Clinica e Tipizzazione TessutaleUniversità Politecnica delle MarcheTorrette di AnconaItaly
  12. 12.Div. A Malattie InfettiveOspedale Amedeo di SavoiaTorinoItaly
  13. 13.Istituto di Clinica Malattie InfettiveUniversità Cattolica del Sacro CuoreRomaItaly
  14. 14.Div. Malattie InfettiveOspedale Policlinico Umberto IRomaItaly
  15. 15.Clinica di Malattie InfettiveOspedale S. Maria della MisericordiaPerugiaItaly
  16. 16.Div. Malattie InfettiveOspedale San GerardoMonzaItaly
  17. 17.Clinica Malattie InfettiveUniversità Tor VergataRomaItaly
  18. 18.INMI “Lazzaro Spallanzani”IV Div. Malattie InfettiveRomaItaly
  19. 19.INMI “Lazzaro Spallanzani”III Div. Malattie InfettiveRomaItaly
  20. 20.Clinica Malattie Infettive e TropicaliUniversità degli Studi di MilanoOspedale San PaoloItaly

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