A pilot study of the use of mycophenolate mofetil as a component of therapy for multidrug-resistant HIV-1 infection

Mycophenolic acid (MPA) increases the activity of both abacavir (ABC) and d idanosine (ddI) in vitro against wild-type and multinucleoside-resistant HI V. We treated 7 patients with diagnosed AIDS who did not respond to eight o r more antiretroviral therapies in an open label pilot study with mycopheno late mofetil (MMF), ABC, ddI, amprenavir (APV), and ritonavir (RTV), with o r without efavirenz (EFV). Therapy was well tolerated despite the patients' advanced disease states. N o significant decline in lymphocyte or other blood counts was observed. Med ian HIV RNA was 5.26 log(10) copies/ml at entry, 4.53 log(10) copies/ml at 4 weeks, and 5.13 log(10) copies/ml at 16 weeks. Median CD4(+) count was 34 cells/mul at entry and 39 cells/mul at 16 weeks of therapy. CD4(+) counts increased further in five study subjects on extended therapy to 25 weeks (m edian 27 cells/mul at entry, 66 cells/mul at close), despite loss of virolo gic suppression in 4 of 5 cases. MPA can induce apoptosis in lymphocytes in vitro. However despite viral rebound, cell surface markers of apoptosis an d activation declined in total CD3(+) cells and CD3(+)/CD4(+) cells twofold to foul fold in 4 of 5 adherent study subjects at 16 weeks, reaching level s comparable with those found in seronegative donors. Although low-dose MMF appears safe in late-stage HIV disease, this study di d not demonstrate virologic efficacy. Higher doses of MMF may be more effec tive. With careful monitoring of toxicities and pharmacokinetics. MMF deser ves further testing in HIV therapy.