A Phase I/II Trial of Vaccine Therapy of HIV-1 Infected Individuals With 50-500 CD4 Cells/mm3

Fifty percent of HIV-1 infected individuals remain symptom free for 8-12 years. It has been hypothesized that HIV-specific immune responses are responsible for the period of relative quiescence of viral replication. Recent studies suggest that these immune functions can be augmented by vaccination with HIV-derived antigens.

Patients are randomized to receive rgp120/HIV-1MN vaccine or alum adjuvant placebo by intramuscular injection at weeks 0, 4, 8, 12, 16, and 20, with or without daily oral zidovudine (AZT) or their current stable dose of antiretroviral therapy. After completing the primary vaccination series, patients are permitted to continue into an extension phase, in which they receive a booster vaccination at weeks 28, 36, and 44. Patients will be stratified by CD4 count: 350-500, 200-349, and 50-199 cells/mm3. A fourth group with counts of 350-500 cells/mm3 will serve as a pilot group and receive vaccine only.

Inclusion criteria

Required immediately prior to study entry:

• A minimum of 2 and a maximum of 12 months of AZT therapy at 500-600 mg/day (does not apply to the pilot group patients receiving vaccine only and to patients with CD4 counts of 50-199 cells/mm3).

Concurrent Medication:

Allowed:

• PCP prophylaxis.
• Rifabutin and clarithromycin (in patients with CD4 counts of 50-199 cells/mm3 only).
• Short-term nonsteroidal anti-inflammatory therapy for acute conditions.
• Short intermittent cycles of acyclovir.

Patients must have:

• HIV infection, with CD4 count of 50-500 cells/mm3.
• No active opportunistic infection (patients with CD4 counts of 50-199 cells/mm3 may have a history of an opportunistic infection).
• Consent of parent, guardian, or person with power of attorney, if less than 18 years of age.
• B-cell lines established in order to be vaccinated.

Exclusion criteria

Co-existing Condition:

Patients with the following symptoms or conditions are excluded:

• Known or suspected allergies to any vaccine components.

Concurrent Medication:

Excluded:

• Agents with immunosuppressive activity.
• Antiretroviral therapies other than AZT (except in patients with CD4 counts of 50-199 cells/mm3).
• Interferon.
• Parenteral therapies (including SC allergy medications and chemotherapy for Kaposi's sarcoma).
• Steroids.
• Hematopoietins.

Prior Medication:

Excluded within 12 weeks prior to study entry:

• Agents with immunosuppressive activity.
• Antiretroviral therapies other than AZT (except in patients with CD4 counts of 50-349 cells/mm3).
• Interferon.
• Parenteral therapies (including SC allergy medications and chemotherapy for Kaposi's sarcoma).
• Steroids.
• Hematopoietins.

Active drug abuse.