Maraviroc as intensification strategy in HIV-1 positive patients with deficient immunological response: An Italian randomized clinical trial

Rusconi, S.; Vitiello, P.; Adorni, F.; Colella, E.; Foca, E.; Capetti, A.; Meraviglia, P.; Abeli, C.; Bonora, S.; D'Annunzio, M.; Di Biagio, A.; Di Pietro, M.; Butini, L.; Orofino, G.; Colafigli, M.; D'Ettorre, G.; Francisci, D.; Parruti, G.; Soria, A.; Buonomini, A. R.; Tommasi, C.; Mosti, S.; Bai, F.; Stuppino, S. D. N.; Morosi, M.; Montano, M.; Tau, P.; Merlini, E.; Marchetti, G.

doi:10.1371/journal.pone.0080157

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. Trial Registration: ClinicalTrials.gov NCT00884858 http://clinicaltrials.gov/show/NCT00884858 © 2013 Rusconi et al.

Maraviroc as intensification strategy in HIV-1 positive patients with deficient immunological response: An Italian randomized clinical trial

Rusconi S.;Vitiello P.;Adorni F.;Colella E.;Foca E.;Capetti A.;Meraviglia P.;Abeli C.;Bonora S.;D'Annunzio M.;Di Biagio A.;Di Pietro M.;Butini L.;Orofino G.;Colafigli M.;D'Ettorre G.;Francisci D.;Parruti G.;Soria A.;Buonomini A. R.;Tommasi C.;Mosti S.;Bai F.;Stuppino S. D. N.;Morosi M.;Montano M.;Tau P.;Merlini E.;Marchetti G.

2013-01-01

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. Trial Registration: ClinicalTrials.gov NCT00884858 http://clinicaltrials.gov/show/NCT00884858 © 2013 Rusconi et al.