IMMUNOLOGICAL EFFICACY OF MARAVIROC (MVC) AS INTENSIFICATION STRATEGY IN HIV-INFECTED PATIENTS (PTS) FAILING CD4 RECOVERY ON VIROLOGICALLY-SUPPRESSIVE HAART

Background: HIV-infected pts failing immune recovery on virologically- suppressive HAART maintain a highly activated/ differentiated peripheral CD4 pool. We hypothesized that MVC, by specifically targeting terminally-differentiated CCR5+CD4, might preserve the naive/central memory CD4 pool in these pts. Methods: Pts on HAART with CD4\200/lL and HIV-RNA\50 cp/ mL were randomized to: HAART+MVC (A) or continuing HAART (B). Na?¨ve CD45RA+62L+, memory CD45RA-, central-memory CD127+, activated/proliferating HLA-DR+CD38+Ki67+CD4/CD8, plasma IL-7 were quantified. HIV-RNA was quantified via Amplicor HIV-1 Monitor Kit v1.5, followed by RT-PCR. Results: 66/100 pts were analyzed at week 12 (W12): 39 in A; 27 in B. At baseline, comparable total CD4 and immune-phenotypes were shown between arms. By W12, both study groups displayed a significant increase in CD4 (A: 184-230, p\.001; B: 165-190, p = .037). A statistically significant change in mean CD8 (p = .002) was observed between pts in arm A and B. HIV-RNA remained \50 cp/mL with no difference between arms. The immunephenotype of reconstituting CD4 was different between arms. Whereas HAARTcontrols displayed a rise in memory CD4 (53-70%, p = .05) with a contraction of naive T-cells (CD4, 24-9%, p = .02; CD8, 20-9%, p = .028), MVC-receiving patients maintained stable memory T-cells (CD4, 35-45%, p = .14; CD8, 35-38%, p = .08) with a non-significant rise in naive CD4 (17-37%, p = .3) and CD8 (11-36%, p = .3). Interestingly, MCV resulted in a significantly higher proportion of na?¨ve CD4 compared to controls (p = .03), whereas controls tended to have higher memory CD4 (p = . 08). Both MVC and HAART resulted in the decline of activated HLA-DR+CD38+ T-cells (A: p = .03, p = .03; B: p = .009, p = .038 for CD4 and CD8, respectively). Despite no changes in Ki67+CD4/CD8 in both groups, MVCreceiving pts displayed significantly lower proliferating Ki67+CD4 at W12 (18 vs. 23% p = .04). As for the IL-7/IL-7R, only MVCreceiving patients presented an increasing trend in central-memory CD127+CD4 by W12 (56-60%, p = .058), with no change in CD127 + CD8 and circulating IL-7. Conclusions: In HIV-infected subjects with inefficient immune reconstitution on virologically-suppressive HAART, intensification with MVC results in a significant expansion of na?¨ve CD4 pool that proliferates less actively. This suggests a reduction in peripheral T-cell death and preserved T-cell production, with possible improvement in immune competence.