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Background:  Mycophenolate mofetil (MMF) reduces the pool of dividing and activated CD4⁺ T cells, contributing to control virus load. A single supervised treatment interruption (sSTI) coupled with MMF might highly reduce the overall need of ART.

Methods:  Since primary HIV-1 infection 15 patients  have been treated with ART for 4.9 ± 0.8 (mean ± SD) years, all achieving optimal suppression of viral load for 3.6 ± 0.7 years. In a prospective controlled study, 15 patients added MMF 500 mg twice daily to ART before USTI (wk –2). ART was stopped at week 0 and MMF 500 mg daily was continued for 24 weeks. If viral load exceeded 100,000 copies/mL, ART was restarted. As controls, 6 well-matched primary HIV-1-infected patients on ART for 2.7 ± 0.2 years and with suppressed viral load for 2.3 ± 0.1 years, underwent sSTI without MMF. Plasma viral load was measured with Nasba-Organon assay (LOD: 80 copies/mL).

Results:  Mean follow-up was 24 months in both groups. After stopping ART, mean of individual highest rebounding viral load peak between weeks 2 and 12 was 3.90 ± 0.26 in the 15 MMF patients vs 5.62 ± 0.21 in the 6 controls (p = 0.001). Following sSTI and MMF, 80% of patients maintained effective viral load control over time, mostly < 5000 copies/mL (see the figure), along with slightly decreasing CD4⁺ T-cell counts (week 0: mean ± SD, 1001 ± 245 cells/μL; week 102: 715 ± 292). Of note, 2 patients had stable viral load < LOD over time. Only 3 of 15 patients restarted ART and stopped MMF, achieving optimal viral load control and increasing CD4⁺ T-cell counts over week 0, suggesting that the use of MMF is safe also in patients who experience high viral load rebound. At variance, 4 of 6 controls restarted ART within the first 12 weeks after sSTI. In the remaining 2 controls, although viral load being < 10,000 at week 102, CD4⁺ T-cell counts substantially decreased at week 102 (–419 and –494 cells/μL over week 0, respectively). Of note, rebound viral load slopes were significantly lower in the 15 MMF patients than in the 6 controls (0.007 vs 0.06 log₁₀ copies/mL, p = 0.006, respectively). MMF was safe in all patients.

Conclusions:  In patients treated with ART during primary HIV-1 infection, the combined use of sSTI and 24-week MMF leads to a remarkably lower viral load rebound than that observed in patients undergoing sSTI alone. In addition, ~80% of sSTI/MMF patients achieved a long-term control of virus replication. Finally, a unique STI along with MMF induces a better outcome than that observed in multiple STI studies without the concomitant use of MMF.

Keywords: PHI; immune-based therapy; MMF