A Pilot, Proof-of-Concept, Dose-Escalating Trial of Recombinant Human Interleukin-12 (rhIL-12) Versus Placebo Along With Paromomycin and Azithromycin for Chronic Cryptosporidiosis in AIDS

Cryptosporidium parvum, an intracellular protozoan parasite, is a frequent cause of chronic diarrhea in HIV-infected patients, causing significant morbidity and mortality. Highly effective antiparasitic treatment for this infection is not currently available. Paromomycin and azithromycin have some efficacy and have been used in combination in a small number of patients. Immune reconstitution with highly active antiretroviral therapy appears to be the most effective therapy, but this is not possible for all patients. Interferon gamma expression is strongly associated with control of cryptosporidiosis, and IL-12 is the cytokine primarily responsible for stimulation of interferon gamma expression in vivo. It is hoped that treatment with recombinant human IL-12 can result in stimulation of an intestinal cytokine response in AIDS patients with cryptosporidiosis and that response combined with chemotherapy can lead to the elimination of detectable numbers of Cryptosporidium oocysts from the stools.

All patients receive azithromycin and paromomycin, and patients are randomized to add either IL-12 or placebo. IL-12 (or placebo) injections are given twice a week. Patients take their study medications for 4 weeks. During this time, they will be asked to record bowel movements and any symptoms they experience. Patients return to the clinic at least twice a week to receive IL-12 (or placebo) injections. At Weeks 2 and 4, patients are seen by one of the principal investigators. Blood samples are obtained for viral load measurements and CD4 count, as well as routine urinalysis. Patients undergo upper endoscopy with jejunal biopsy and colonoscopy with ileal biopsy between Weeks 2 and 4 of therapy for assays of intestinal cytokine expression. A final clinic visit occurs 12 weeks post-therapy for a physical exam and blood tests.