A Phase I Study of Methotrexate for HIV Infection

Inclusion Criteria Concurrent Medication: Allowed: Antiemetics and antidiarrheals. Acetaminophen. Oral hypoglycemic agents. PER AMENDMENT 5/15/96: Stable dose of antiretroviral (must be stable for at least 1 month prior to study entry). [AS PER AMENDMENT 1/10/97: Combination zidovudine/lamivudine or zidovudine alone.] Patients must have: HIV seropositivity. CD4 count >= 300 cells/mm3. No AIDS-defining condition. Exclusion Criteria Co-existing Condition: Patients with the following symptom or condition are excluded: Current positive PPD. Concurrent Medication: Excluded: Immunosuppressive or immunomodulatory drugs. Chronic nonsteroidal anti-inflammatory agents. Newly initiated antiretrovirals. Bone marrow suppressive drugs (e.g., TMP/SMX). Concurrent Treatment: AS PER AMENDMENT 1/10/97: Excluded: Antiretroviral therapy other than combination zidovudine/lamivudine or zidovudine alone; no initiation of other antiretroviral therapy should be planned while patient is on methotrexate. Patients with the following prior conditions are excluded: Prior malignancies. Prior mucocutaneous herpes infection requiring antiviral therapy [AS PER AMENDMENT 7/31/96: Prior mucocutaneous herpes infection requiring systemic treatment with an antiviral agent (e.g., acyclovir); history of topical antiviral therapy is permitted]. Anergic on DTH skin test within the past month (PER AMENDMENT 5/15/96: patients who are positive on DTH skin test but unable to receive the HIV-1 skin test because of allergies to insects, bee stings, etc., remain eligible for study enrollment). Inflammatory bowel disease, peptic ulcer disease, obesity combined with insulin-requiring diabetes, liver disease, or chronic renal disease within the past 6 months. Positive for HBsAg or hepatitis C antibody within the past 2 weeks. Chest radiograph within the past 60 days that shows cavity disease, infiltrates, or scars from prior disease that would preclude diagnosis of a new infectious process or drug-induced pneumonitis. AS PER AMENDMENT 1/10/97: History of intolerance to zidovudine or lamivudine. Prior Medication: Excluded: Prior chemotherapy for malignancy. Prior Treatment: Excluded: Prior radiotherapy for malignancy. Alcohol abuse.