658a Mycophenolate Mofetil Does Not Have an Additional Effect on Plasma HIV-RNA Decay and on the Pool of Latently Infected Resting CD4+ T Lymphocytes in Therapy Naïve HIV-1 Patients Starting HAART S. Sankatsing*1,2, S. Jurriaans2, H. Schuitemaker3, M. Cornelissen2, L. van Weert 1, J. Lange1,2, J. Prins2 1International Antiviral Therapy Evaluation Center, Amsterdam, The Netherlands; 2Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands; and 3Sanquin Research and Landsteiner Laboratory, University of Amsterdam, Amsterdam, The Netherlands
Background Recent studies suggest a potential role for mycophenolate mofetil (MMF) in the treatment of HIV-1. By inhibiting the de novo synthesis of cellular guanosine, MMF limits lymphocyte proliferation and the availability of target cells for HIV infection. When added to HAART, a significant decrease of the latently infected cellular reservoir has been reported. In vitro MMF also has a direct anti-HIV-1 effect and increases the efficacy of abacavir. We studied plasma HIV-1 RNA decay and the latent cellular reservoir in treatment naïve patients starting HAART with or without MMF.
Methods 18 HIV-1 patients (8 with a chronic and 10 with a primary HIV-1 infection) started with a triple class 5 drug regimen consisting of didanosine 400 mg QD, lamivudine 150 mg BID, abacavir 300 mg BID, indinavir 800 mg BID, ritonavir 100 mg BID and nevirapine 200 mg BID. They were randomised to a group with or without MMF 500 mg BID. Plasma samples for HIV-1 RNA were taken at day 0, (in case of a primary infection also on day 5), week 1, 2, 4, 8, 12, 16 and every 8 weeks thereafter. At day 0, week 1, 2, 4, 8, 16 and 24 HLA-DR-CD4+ T cells were co-cultured for HIV-1 isolation. The slope of the plasma HIV-RNA decay was calculated for the first 14 days of treatment and the slope of the cellular viral load decay was calculated for the first 24 weeks of treatment.
Results Plasma HIV-RNA dropped below 50 copies/mL after 3-24 weeks of treatment in chronically and after 2-25 weeks in primary infected HIV patients. The median plasma HIV-RNA decay (log10 HIV-RNA copies/mL/day) was 0.25 (0.18-0.30) and 0.28 (0.22-0.32) in chronically infected patients with and without MMF respectively (p=0.56) and 0.31 (0.31-0.32) and 0.32 (0.26-0.34) in primary infected patients with and without MMF (p=0.75). The median slope of the decay (number of infected cells/1 X 106 cells/day) of the latently infected cellular reservoir was 0.060 (0.034-0.079) and 0.023 (0.010-0.051) in chronically infected patients with and without MMF respectively (p=0.15) and 0.003 (-0.011-0.015) and 0.064 (0.007-0.071) in primary infected patients with and without MMF (p=0.17). Absolute numbers of CD4+ and CD8+ T-cells and their subsets did not differ with or without MMF.
Conclusion The addition of MMF to a triple class antiretroviral regimen in treatment naïve patients does not increase the plasma HIV-1 RNA decay or the decay of the latently infected cellular reservoir during the first 24 weeks of treatment.
