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

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/mu L 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/mu L and CD4>200/mu L + 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.