BACKGROUND: Immunological non-responders (INRs) lacked CD4 increase despite HIV-viremia suppression on HAART and had an increased risk of disease progression. We assessed immune reconstitution profile upon intensification with maraviroc in INRs. METHODS: We designed a multi-centric, randomized, parallel, open label, phase 4 superiority trial. We enrolled 97 patients on HAART with CD4+<200/µL and/or CD4+ recovery ≤25% and HIV-RNA<50 cp/mL. Patients were randomized 1:1 to HAART+maraviroc or continued HAART. CD4+ and CD8+ CD45+RA/RO, Ki67 expression and plasma IL-7 were quantified at W0, W12 and W48. RESULTS: By W48 both groups displayed a CD4 increase without a significant inter-group difference. A statistically significant change in CD8 favored patients in arm HAART+maraviroc versus HAART at W12 (p=.009) and W48 (p=.025). The CD4>200/µL and CD4>200/µL + CD4 gain ≥25% end-points were not satisfied at W12 (p=.24 and p=.619) nor at W48 (p=.076 and p=.236). Patients continuing HAART displayed no major changes in parameters of T-cell homeostasis and activation. Maraviroc-receiving patients experienced a significant rise in circulating IL-7 by W48 (p=.01), and a trend in temporary reduction in activated HLA-DR+CD38+CD4+ by W12 (p=.06) that was not maintained at W48. CONCLUSIONS: Maraviroc intensification in INRs did not have a significant advantage in reconstituting CD4 T-cell pool, but did substantially expand CD8. It resulted in a low rate of treatment discontinuations.

Maraviroc as Intensification Strategy in HIV-1 Positive Patients with Deficient Immunological Response: an Italian Randomized Clinical Trial / S. Rusconi, P. Vitiello, F. Adorni, E. Colella, E. Focà, A. Capetti, P. Meraviglia, C. Abeli, S. Bonora, M. D'Annunzio, A. Di Biagio, M. Di Pietro, L. Butini, G. Orofino, M. Colafigli, G. d'Ettorre, D. Francisci, G. Parruti, A. Soria, A.R. Buonomini, C. Tommasi, S. Mosti, F. Bai, S. Di Nardo Stuppino, M. Morosi, M. Montano, P. Tau, E. Merlini, G. Marchetti. - In: PLOS ONE. - ISSN 1932-6203. - 8:11(2013 Nov 14), p. e80157.e80157. [10.1371/journal.pone.0080157]

Maraviroc as Intensification Strategy in HIV-1 Positive Patients with Deficient Immunological Response: an Italian Randomized Clinical Trial

S. Rusconi;P. Vitiello;E. Colella;A. Capetti;F. Bai;M. Morosi;P. Tau;E. Merlini;G. Marchetti
2013-11-14

Abstract

BACKGROUND: Immunological non-responders (INRs) lacked CD4 increase despite HIV-viremia suppression on HAART and had an increased risk of disease progression. We assessed immune reconstitution profile upon intensification with maraviroc in INRs. METHODS: We designed a multi-centric, randomized, parallel, open label, phase 4 superiority trial. We enrolled 97 patients on HAART with CD4+<200/µL and/or CD4+ recovery ≤25% and HIV-RNA<50 cp/mL. Patients were randomized 1:1 to HAART+maraviroc or continued HAART. CD4+ and CD8+ CD45+RA/RO, Ki67 expression and plasma IL-7 were quantified at W0, W12 and W48. RESULTS: By W48 both groups displayed a CD4 increase without a significant inter-group difference. A statistically significant change in CD8 favored patients in arm HAART+maraviroc versus HAART at W12 (p=.009) and W48 (p=.025). The CD4>200/µL and CD4>200/µL + CD4 gain ≥25% end-points were not satisfied at W12 (p=.24 and p=.619) nor at W48 (p=.076 and p=.236). Patients continuing HAART displayed no major changes in parameters of T-cell homeostasis and activation. Maraviroc-receiving patients experienced a significant rise in circulating IL-7 by W48 (p=.01), and a trend in temporary reduction in activated HLA-DR+CD38+CD4+ by W12 (p=.06) that was not maintained at W48. CONCLUSIONS: Maraviroc intensification in INRs did not have a significant advantage in reconstituting CD4 T-cell pool, but did substantially expand CD8. It resulted in a low rate of treatment discontinuations.
Settore MED/17 - Malattie Infettive
PLOS ONE
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/2434/228716
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