Background:  Mycophenolate mofetil (MMF) reduces the pool of dividing and activated CD4⁺ T cells, contributing to control virus load. Impact on VIRUS LOAD and CD4⁺ T cell counts of a unique supervised treatment interruption coupled with MMF is assessed in a non-randomised controlled study.

Methods: Since primary HIV-1 infection 14 patients have been treated with HAART for 4.9±0.8 (mean ±SD) years, all achieving optimal suppression of virus load for 3.6±0.7 years. Before unique supervised treatment interruption, all patients added MMF 500 mg twice daily to HAART at week 2. At week 0 HAART was stopped and MMF 500 mg every day was continued for 24 weeks. If virus load exceeded 100,000 copies/mL, HAART was restarted. As controls, 6 well-matched primary HIV-1 infection patients on HAART for 2.7±0.2 years and with suppressed virus load for 2.3±0.1 years, underwent unique supervised treatment interruption without MMF. Plasma virus load was measured with Nasba-Organon assay (LOD:  80 copies/mL).

Results:  All patients have been followed for at least 48 weeks. The matrix below shows each virus load determination in the MMF group over time depicted in varying colours according to virus load categories.

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Following unique supervised treatment interruption and MMF, 11 of 14 patients have maintained a very effective virus load control over time, mostly <5000 copies/mL, along with stable or decreasing levels of HIV-1 DNA, and slightly decreasing CD4⁺ T-cell counts (week 0: mean ±SD, 1020±266 cells/mL; week 48: 805±185). Only 3 of 14 patients (#12 to 14) discontinued MMF and restarted HAART, achieving optimal virus load control and increasing CD4⁺ T-cell counts over week 0, whereas 4 of 6 controls restarted HAART within the first 12 weeks after unique supervised treatment interruption, and the remaining 2 controls had virus load of 35,000 and 5000 copies/mL, respectively, with a substantial decrease in CD4⁺ T-cell counts at week 48 (-444 and -373 cells/mL over week 0, respectively). Of note, rebound virus load slopes were significantly lower in the 14 MMF patients than in controls (slope to the highest virus load value: +755 vs +10,214 copies/mL/day, respectively, p = 0.03; slope to week 4: +657 vs +12,098 copies/mL/day, respectively, p = 0.01).

Conclusions:  Unlike unique supervised treatment interruption alone, unique supervised treatment interruption and 24-week MMF in combination are associated with a long-term control of virus replication in >75% of cases. Studies on changes in pathogen-specific helper and cytotoxic effector T cells are currently being performed.

Keywords: STI; MMF; PHI