656 The Addition of Mycophenolate Mophetil (MMF) to HAART in Early Stage HIV-infected Patients Is Associated with a Probable Decrease in Viral Reservoir Size F. García*, M. Plana, M. Brunet, M. Arnedo, C. Gil, E. Vidal, G. Mestre, J. Martorell, J. M. Miró, J. Mallolas, J. L. Blanco, E. Martínez, T. Pumarola, T. Gallart, J. M. Gatell Inst d'Investigacions Biomèdiques August Pi i Sunyer, Hosp Clin, Univ of Barcelona, Spain
Background: To study the effect of associating MMF+HAART on plasma and tonsillar tissue viral load (TTVL). The PK and inhibition of lymphocyte proliferation (CEM response) of MMF and the effect on viral load rebound after HAART interruption were also assessed.
Methods: Seventeen (17) CHI patients (pts) in very early stage (BVL 200-5,000 c/ml and CD4+ >500) were treated with abacavir+efavirenz+nelfinavir for 12 months (mos). Thereafter, they were randomized (day 0) to receive the same HAART+MMF (0.25 g bid) (MMF group, n = 9) vs the same HAART (ART group, n = 8) during 4 additional mos. Two (2) pts of control group were lost for follow-up. Thereafter HAART was discontinued (day 120).
Results: At day 120 all the pts had an undetectable level of PVL (< 5c/ml) and TTVL. The median for AUC0-12h of MMF was around 15 mg*hr/L. CEM response decreased to 45% in all time-points in 6 out of 9 pts, but not in the remaining 3 pts. We compared viral load rebound in the 6 pts with decreased CEM response (inh-group) vs 3 pts without decreased of CEM response (n = 3) plus control group (n = 6) (no-inh group). After 1 mo of interruption of HAART, PVL, and TTVL increased above detectable level in 0/6 pts of inh-group and in all 9 pts of the no-inh-group (p = 0.0001). After interruption of HAART, doubling time was significantly higher in the inh-group 10.22 ±1.3 than in no-inh group 4.6 ±1.6 (p = 0.03). AUC of viral rebound was significantly lower in the inh-group 0.82 ±0.23 than in no-inh group 1.92 ±0.2 (p = 0.003). There were no significant differences in peak of PVL after interruption (p = 0.28). At day 120, there was no differences between MMF and ART groups neither in lymphocyte subset tested (CD4+, CD8+, naive and memory, CD8+CD28+ and CD8+CD38+ T-cells) nor in Ki67+ cells or anexin levels. After interruption of HAART, there was an increase of Ki67+ cells (p = 0.05) and this increase was significantly lower in inh-group (AUC: 0.98 ±0.27) than in no-inh group (AUC 1.94 ±0.35)(p = 0.05). Anexin levels did not change over all the time-point tested (p = 0.28).
