658 Patterns of Viral Rebound and CD4 Slopes in Patients with Primary HIV-1 Infection with Persistent Undetectable Viremia Treated with Supervised Treatment Interruption Plus Mycophenolate Mofetil G. Tambussi*1, G. P. Rizzardi1, A. Lazzarin1, G. Pantaleo2 1HSR Hosp San Raffaele, Milan, Italy and 2CHUV Lausanne, Switzerland
Background: This pilot, non-randomized study aims at assessing the effect of the addition of mycophenolate mofetil (MMF) during supervised interruption of therapy (STI) on virus rebound and CD4 T-cell counts. It is conceivable that MMF may reduce the pool of dividing and activated CD4 T-cells, contributing to achieve a better control of virus replication.
Methods: Fifteen (15) subjects (12 males, 3 females) with PHI were prospectively treated with antiviral therapy (ART) for 58.5 ±9.1 (mean ±SD) months (mos). All patients (pts) showed optimal suppression of virus load (VL) for 43.5 ±8.8 mos. Pts were treated with MMF 500 mg bid plus ART for 14 days prior to the interruption of therapy. At day 0, ART was stopped and MMF, halved to 500 mg qd, was continued for 24 wks. According to the protocol, ART was restarted if VL exceeded 100,000 copies/ml. As control group, 6 well-matched pts on ART for 32.2 ±2.2 mos and with suppressed VL for 27.6 ±1.9 mos, underwent STI without MMF. Plasma VL was measured with Nasba-Organon assay (LOD: 80 copies/ml).
Results: The preliminary analysis refers to 16 pts (10 in the MMF group and 6 controls) at 24 wks of follow-up after treatment interruption. In the MMF group, MMF was stopped and ART was reintroduced in 2 pts, 12 and 20 wks after ART interruption, respectively. One pt, still on MMF alone, had poor control of VL (85,000 copies/ml at wk 24) maintaining CD4 T-cell count greater than 1000 cells/mm3. Among the remaining 7 pts, 1 pt optimally controlled VL (< 80 copies/ml), 2 effectively controlled VL (780 and 1,300 copies/ml, respectively), and 4 partially controlled VL (9,000, 7,200, 4,900, and 4,600 copies/ml, respectively). In these 7 pts, CD4 T-cell counts were stable between day 0 (mean ±SD, 972 ±211) and wk 24 (855 ±271). In the control group, 4 out of 6 pts needed to restart ART within the first 12 wks after STI. At wk 24, the 2 remaining subjects had VL of 28,900 and 1,871 copies/ml, respectively, though with a substantial decrease CD4 T-cell counts (-367 and -194 cells/mm3, over the day 0 value, respectively).
Conclusions: The combination of STI plus MMF therapy appears to be associated with a substantial control of virus replication in 7 out of 10 pts, whereas no control of virus replication was observed in the STI control group. The immunologic characterization of the pts in the STI+MMF and STI groups is currently being performed and will be presented at the meeting.
