534-M. Effect of Associating an Immunosuppressive Therapy (Mycophenolate Mofetil: MMF)+HAART during STI and Holding the MMF Drug after Definitive Interruption of HAART on Viral Replication

Abstract

E-mail Abstract Author

Add To Itinerary

Session

Search Abstracts

Program

Session 72 Poster Session
Treatment Interruption
Session Time: 4:30-6:30 pm
Room 4E-F

534-M.

Effect of Associating an Immunosuppressive Therapy (Mycophenolate Mofetil: MMF)+HAART during STI and Holding the MMF Drug after Definitive Interruption of HAART on Viral Replication
F. García¹, M. Plana*¹, M. Brunet¹ , M. Arnedo¹, J. Alcami², C. Lopez-Galindez², K. Tenner-Racz³, C. Gil¹, E. Vidal¹, G. Mestre¹, J. Martorell¹, A. Cruceta¹, J. Miró¹, T. Pumarola¹, T. Gallart¹, P. Racz³, and J. M. Gatell¹
¹Univ. of Barcelona, Spain; ²Inst. Carlos III, Madrid, Spain; and ³Bernhard-Nocht-Inst., Hamburg, Germany

Background: To study the effect of associating MMF+HAART and holding MMF after cycles of STI on plasma and tonsillar tissue viral replication (TTVL). The PK of MMF and the effect on lymphocyte subsets and proliferative responses (LPR) were also assessed.
Methods: 15 CHI patients in very early stage (BVL 200-5000 copies/mL and CD4+ >500) were treated with abacavir+efavirenz+nelfinavir for 12 months. Thereafter, they were randomized (day 0) to receive the same HAART+MMF (0.25g BID) (MMF group, n=9) vs the same HAART (ART group, n=6) during 4 additional months. Thereafter HAART was discontinued (day 120) holding MMF in the MMF group. HAART was reintroduced during 4 months if viral load was > 200 copies/mL after 3 months of stop.
Results: At day 120 all the patients had an undetectable level of PVL (<5 copies/mL) and TTVL. At day 150, PVL and TTVL increased above detectable level in 3/9 patients of MMF group and in all 6 patients of the ART group (p=0.01). 5 of 9 patients in MMF group vs 5/6 patients of ART group had to perform a second cycle of STI due to increase of VL >200 copies/mL. There was a trend to have a VL set-point lower in MMF group than in ART group (median: 326 vs 1432 copies/mL, respectively, p= 0.10). At day 120, there was no differences between MMF and ART groups neither in lymphocyte subset tested (CD4+, CD8+, naïve and memory, CD8+CD28+ and CD8+CD38+ T cells) nor in LPR. After last cycle of STI, there was an increase of Ki-67+ cells, without difference between MMF and ART groups. Anexin levels did not change over all the time-points tested. The median value obtained for AUC0-12h was around 15 and CEM response decreased to around 45% on all time-points.
Conclusions: Associating MMF + HAART and holding MMF after cycles of STI delayed the viral load rebound both in plasma and tonsillar tissue and improve the control of viral replication without HAART. This effect does not seem mediated by a decrease in cell turnover nor by an increase in apoptosis.