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  • Oral presentation
  • Open Access

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

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Journal of the International AIDS Society201013 (Suppl 4) :O44

https://doi.org/10.1186/1758-2652-13-S4-O44

  • Published:

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).

Authors’ Affiliations

(1)
Dipartimento di Scienze Cliniche “Luigi Sacco”, Sezione di Malattie Infettive-Immunopatologia, Università degli Studi di Milano, via GB Grassi, 74, Milano, Italy
(2)
ITB-CNR, Segrate, MI, Italy
(3)
Clinica Malattie Infettive, Università degli Studi di Brescia, Spedali Civili, Brescia, Italy
(4)
1a Div. Malattie Infettive, Ospedale Luigi Sacco, Milano, Italy
(5)
2a Div. Malattie Infettive, Ospedale Luigi Sacco, Milano, Italy
(6)
Div. Malattie Infettive, Ospedale di Circolo, Busto Arsizio, VA, Italy
(7)
Clinica Malattie Infettive, Università degli Studi di Torino, Torino, Italy
(8)
Clinica di Malattie Infettive, Ospedale Policlinico di Bari, Bari, Italy
(9)
Clinica Malattie Infettive, Università degli Studi di Genova, Ospedale San Martino, Genova, Italy
(10)
Div. Malattie Infettive, Ospedale S. Maria Annunziata, Antella, FI, Italy
(11)
Servizio Regionale di Immunologia Clinica e Tipizzazione Tessutale, Università Politecnica delle Marche, Torrette di Ancona, AN, Italy
(12)
Div. A Malattie Infettive, Ospedale Amedeo di Savoia, Torino, Italy
(13)
Istituto di Clinica Malattie Infettive, Università Cattolica del Sacro Cuore, Roma, Italy
(14)
Div. Malattie Infettive, Ospedale Policlinico Umberto I, Roma, Italy
(15)
Clinica di Malattie Infettive, Ospedale S. Maria della Misericordia, Perugia, Italy
(16)
Div. Malattie Infettive, Ospedale San Gerardo, Monza, Italy
(17)
Clinica Malattie Infettive, Università Tor Vergata, Roma, Italy
(18)
INMI “Lazzaro Spallanzani”, IV Div. Malattie Infettive, Roma, Italy
(19)
INMI “Lazzaro Spallanzani”, III Div. Malattie Infettive, Roma, Italy
(20)
Clinica Malattie Infettive e Tropicali, Università degli Studi di Milano, Ospedale San Paolo, Milano, Italy

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