The Effectiveness of Three Anti-HIV Drug Combinations in HIV-Infected Patients Who Have Never Used Anti-HIV Drugs

A Phase II Randomized Study of the Virologic and Immunologic Effects of Zidovudine Plus Lamivudine (3TC) Versus d4T Versus Zidovudine Plus d4T in HIV-Infected Patients With CD4 Cell Counts Between 300-600/mm3 and No Previous Nucleoside Experience

To determine drug efficacy and safety in HIV-infected patients treated with zidovudine ( AZT ) versus stavudine ( d4T ) versus both drugs. Also, to compare short- and long-term changes in magnitude of HIV RNA over time.

Asymptomatic patients with CD4 counts over 300 cells/mm3 are more likely to tolerate any of the nucleoside analogs. d4T, with a favorable toxicity profile and demonstrated anti-HIV activity in previous studies, provides an additional therapeutic option.

Asymptomatic patients with CD4 counts over 300 cells/mm3 are more likely to tolerate any of the nucleoside analogs. d4T, with a favorable toxicity profile and demonstrated anti-HIV activity in previous studies, provides an additional therapeutic option.

Patients are randomized to receive d4T alone, AZT alone, or both in combination for at least 12 weeks. After week 12, 3TC is added to the combination arm. Treatment continues for up to 48 weeks (was a total of 48 weeks, amended 3/26/96).

Inclusion Criteria

Concurrent Medication:

Required:

• TMP / SMX, aerosolized pentamidine, or dapsone for PCP prophylaxis.

Allowed:

• Atovaquone.
• IV pentamidine.
• TMP / SMX.
• Trimetrexate.
• Trimethoprim-dapsone.
• Clindamycin-primaquine.
• Topical antifungals.
• Clotrimazole.
• Ketoconazole.
• Fluconazole.
• Amphotericin B.
• Itraconazole.
• Rifabutin.
• Isoniazid.
• Pyrazinamide.
• Clofazimine.
• Clarithromycin.
• Azithromycin.
• Ethambutol.
• Amikacin.
• Ciprofloxacin.
• Ofloxacin.
• Pyrimethamine.
• Sulfadiazine.
• Clindamycin.
• Filgrastim ( G-CSF ).
• Up to 1000 mg/day acyclovir.
• Erythropoietin.
• Antibiotics.
• Antipyretics.
• Analgesics.
• Antiemetics.
• Rifampin.

Concurrent Treatment:

Allowed:

• Local radiation therapy.

Patients must have:

• HIV infection.
• CD4 count 300 - 600 cells/mm3.
• NO history of AIDS.
• NO active opportunistic infection.
• NO prior nucleoside therapy.
• Life expectancy at least 2 years.

Exclusion Criteria

Co-existing Condition:

Patients with the following symptoms or conditions are excluded:

• Serious underlying medical condition other than HIV such that life expectancy is less than 2 years.
• Malignancy requiring systemic cytotoxic chemotherapy.
• Active grade 2 or worse peripheral neuropathy.

Concurrent Medication:

Excluded:

• Antiretrovirals other than study drugs.
• Systemic cytotoxic chemotherapy.
• Foscarnet.

Patients with the following prior conditions are excluded:

• Chronic diarrhea defined as three or more stools per day for 15 days, within 30 days prior to study entry.
• Unexplained temperature >= 38.5 C for any 7 days within 30 days prior to study entry.
• Active participation in other experimental therapy within 30 days prior to study entry.

Prior Medication:

Excluded:

• Prior nucleoside antiretrovirals of 1 week or longer duration.
• Any antiretroviral within 90 days prior to study entry.
• Non-nucleoside reverse transcriptase inhibitors and protease inhibitors within 30 days prior to study entry.
• Biologic response modifiers such as IL-2 and interferon within 30 days prior to study entry.