Efficacy of Maraviroc (MVC) as intensification strategy in immunological non-responder (INR) HIV-1-infected patients treated with HAART

Background: Under HAART, 7-39% of HIV-infected patients (pts) fail to exhibit a recovery in CD4 cells despite full suppression of viral replication. In MOTIVATE trials, MVC was superior to OBT in increasing CD4 cells in ARV-experienced pts. This study evaluated the clinical efficacy of MVC in terms of CD4 cells recovery, viral replication and tolerability in INR pts. Methods: Randomised, multicentre, proof of concept study enrolling 100 pts divided into 2 arms: A HAART+MVC, B HAART. Planned F-U is 1 year. Ultrasensitive HIV-RNA was quantified via Amplicor HIV-1 Monitor Kit v1.5, followed by RT-PCR for quantifying 1-50 cp/mL. Naive CDRA+62L+, memory CD45RA-, activated HLADR+ CD38+, proliferating Ki67+ were measured by flow cytometry. T-test was used for intra and inter-group comparisons. ANCOVA was used to adjust the baseline values. Results: 100 pts have been randomized (50 pts/arm). 59 pts reached week 12: 30 in arm A and 29 in arm B. 2 HIV-unrelated clinical events were registered in arm B and 2 in arm A (not known the correlation with MVC administration) as well as 9 drop-outs at baseline (withdrawal of the informed consent). No grade 3-4 lab toxicity were reported. At baseline, CD4/CD8 and immune-phenotype was comparable in arm A and B. At week 12, no significant changes in mean CD4 recovery were seen between pts in arm A and B (+41,2 vs -11,6/?l; p=.12). A statistically significant change was observed in mean CD8+ count between pts in arm A and B (+99,3 vs -126,1/?l, p=.025) At baseline and week 12 an immunological study performed by flow cytometry was carried out in 24 out of 61 pts (13 in arm A, 11 in arm B): at week 12, while B pts experienced a progressive contraction of naive 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 week 12, 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). No changes were shown in proliferating Ki67+CD4 in A (p=.42) and B pts (p=.47), while a tendency 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 week 12) in B pts: 2 vs 5 cp/mL (p=.37). No changes occurred in arm A. Conclusions: we can consider the use of MVC as intensification strategy that seems to impact T-cell peripheral immune-phenotype after examining the significant change in CD8* cells count and the evidence of not significant CD4 gain in arm A.Our findings of reduced loss of naive T-cells with a parallel robust rise in the memory pool suggest a role of MVC in reducing peripheral antigen-driven T-cell death, possibly preserving new T-cell production. However, further data are needed to confirm our results.