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.