The purpose of this study is to see if it is safe and effective to add interleukin-12
(IL-12) to the standard drug combination (paromomycin plus azithromycin) used to treat
cryptosporidiosis in AIDS patients. Doctors would like to find out if the combination of
IL-12, paromomycin, and azithromycin is more effective than paromomycin and azithromycin
Cryptosporidiosis is a type of opportunistic (AIDS-related) infection seen in HIV-positive
patients as their immune systems weaken. It is caused by a parasite that invades the
intestinal tract, and it can cause watery diarrhea, stomach cramps, an upset stomach, or a
fever. Antibiotics (paromomycin and azithromycin) are usually used to treat
cryptosporidiosis. In this study, doctors will look at the effectiveness of using IL-12.
IL-12 is a type of protein naturally produced by certain types of cells of the immune system
and is believed to be important for immune function. Doctors hope that IL-12 can help boost
the immune system in fighting cryptosporidiosis.
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.
Patients may be eligible for this study if they:
- Are HIV-positive.
- Have a CD4 cell count below 150 cells/mm3.
- Have been on stable anti-HIV therapy that includes at least 2 nucleoside analogues
for at least 4 weeks.
- Have chronic diarrhea (3 bowel movements a day that are loose or watery, for 5 days
per week over 3 weeks).
- Test positively for Cryptosporidium.
- Are at least 18 years old.
- Agree to use effective methods of birth control.
Patients will not be eligible for this study if they:
- Have any other active opportunistic (AIDS-related) infection.
- Require intravenous (IV) fluids.
- Have a history of an allergy to certain medications, such as colony-stimulating
factors (G-CSF or GM-CSF) or a type of antibiotic.
- Are pregnant.