A Phase I/II, Open Label Study to Evaluate the Antiviral Potential of Combination Zidovudine and 2' 3'-Dideoxyinosine (Didanosine) in Patients With Asymptomatic HIV Disease

Inclusion Criteria

Concurrent Medication:

Allowed:

   - Aerosolized pentamidine.

   - Acute and intermittent therapy with mycostatin and mycelex.

   - Isoniazid, if no alternative therapy is available.

Allowed for up to 2 weeks:

   - Acyclovir for Herpes infection (withhold didanosine during therapy).

   - Acute therapy with fluconazole or ketoconazole.

Allowed but preferably not on a continuous basis for > 72 hours:

   - Acetaminophen.

   - Ibuprofen.

   - Nonsteroidal antiinflammatory agents.

Patients must be:

   - HIV antibody positive.

   - Asymptomatic or have persistent generalized lymphadenopathy.

   - Diagnosed with one of the listed coagulopathies.

   - OR Sexual partner of someone with the above criteria.

Allowed:

   - Basal cell carcinoma or in situ carcinoma of the cervix.

NOTE:

   - As of January, 1991 full accrual of patients with prior AZT use has been reached - NOW
   ACCRUING ONLY THOSE WITH NO PRIOR AZT USE. Hemophilia restriction has been lifted.

Prior Medication:

Allowed:

   - Zidovudine (AZT) for a total of = or < 13 months.

NOTE:

   - As of January, 1991 accrual of these patients was reached, NOW ONLY PATIENTS WITH NO
   PRIOR AZT.

Exclusion Criteria

Co-existing Condition:

Patients with the following conditions or symptoms are excluded:

   - Unexplained temperature > 38 degrees C for more than 5 consecutive days or on more
   than 10 days in any 30-day period in the 2 years prior to study entry.

   - Unexplained diarrhea defined as at least 3 liquid stools/day persisting more than 7
   days within 2 years prior to study entry.

   - Unintentional weight loss of > 10 pounds or > 10 percent of usual body weight within 2
   years prior to study entry.

   - Oral hairy leukoplakia at any time prior to study entry.

   - Recurrent oral candidiasis unrelated to the use of antibiotics within 2 years prior to
   entry or unrelated to the use of antibiotics within the past 3 months.

   - Herpes zoster within 2 years prior to study entry.

   - Seizures within the past 6 months or currently requiring anticonvulsants for control.

   - Current heart disease.

   - Current psychological or emotional problems sufficient in the investigator's opinion
   to prevent adequate compliance with study therapy.

   - Gout.

Concurrent Medication:

Excluded:

   - Rifampin.

   - Chemoprophylaxis for Pneumocystis carinii pneumonia other than aerosolized
   pentamidine.

   - Intravenous pentamidine.

   - Other antiretroviral agents, experimental medication, biological response modifiers,
   systemic corticosteroids, cimetidine, and ranitidine.

   - Barbiturates.

   - Oral acidifying agents.

Patients with a history of any of the following are excluded:

   - AIDS-defining opportunistic infection, advanced AIDS-related complex, or malignancy.

   - Acute or chronic pancreatitis.

   - Grade 2 or higher neuropathy based on the Neuropathy Targeted Symptom Questionnaire.

   - Seizures.

   - Zidovudine therapy for = or > 13 months.

   - Heart disease.

   - Psychological or emotional problems sufficient in the investigator's opinion to
   prevent adequate compliance with study therapy.

   - Gout.

Prior Medication:

Excluded within 4 weeks of study entry:

   - Antiretroviral agents, including ribavirin, HPA-23, rifampin, AL721.

   - Excluded within 3 months of study entry:

   - Significant course of immunomodulating agents, such as steroids (> 1 week),
   isoprinosine, thymic factors, or any other experimental drugs.

   - Excluded within 30 days prior to study entry:

   - Neurotoxic drugs.

Excluded:

   - Didanosine (ddI).

   - Dideoxycytidine (ddC).

   - Zidovudine (AZT) if received for > 13 months.

Prior Treatment:

Excluded within 3 months of entry:

   - Other experimental therapy.

History of recent alcohol abuse.