Safety of the Candidate Vaccine C4-V3 Alone or With Interleukin-12 (IL-12) in HIV-Infected Patients Receiving Effective Anti-HIV Drug Therapy

The purpose of this study is to see if it is safe to give C4-V3, a possible HIV vaccine, alone or in conjunction with 4 different doses of interleukin-12 (IL-12), to HIV-infected patients who are taking anti-HIV drugs that have lowered the amount of HIV in patients' blood. (This study has been changed so that vaccine is administered alone or with 4 different doses of IL-12.) Immune cells known as cytotoxic T lymphocytes (CTLs) help destroy HIV-infected cells. However, in most patients, CTLs decrease over time. This allows HIV levels to rise and AIDS symptoms to develop. The C4-V3 vaccine contains small pieces of HIV protein that can boost CTL levels, allowing the body's immune system to fight HIV. Giving IL-12, a normal part of the immune system, with C4-V3 may make the vaccine more effective.

Cytotoxic T lymphocyte (CTL) responses are important to the initial decrease in HIV viral load seen in the first several months after acute infection. These beneficial CTL responses diminish with disease progression and cannot be recovered with antiretroviral therapy alone. Recent studies suggest a vaccine may help restore CTL responses. This study tests the effectiveness of the C4-V3 vaccine, a synthetic peptide vaccine representing 4 epitopes from HIV gp120, including an HLA B7-restricted CTL epitope. Administering IL-12, an immunostimulatory cytokine, in conjunction with C4-V3 may enhance HIV-1 specific immune responses and global immune function. All patients continue their antiretroviral regimen during the study. Twelve patients are assigned equally to 1 of 3 cohorts; all patients receive 4 doses of C4-V3. Cohort 1 receives C4-V3 alone; once all 4 patients have received 2 doses and completed 8 weeks of treatment, toxicity data are reviewed. Barring serious adverse events, 4 patients are enrolled in Cohort 2 to receive C4-V3 plus a low dose of IL-12 near the vaccine injection sites. Once all 4 patients have received 2 doses of C4-V3/IL-12 and completed 8 weeks of treatment, toxicity data are reviewed. Barring serious adverse events, 4 patients are enrolled in Cohort 3 to receive C4-V3 plus a higher dose of IL-12 administered as above. \[AS PER AMENDMENT 8/1/00: Twenty patients are assigned equally to 1 of 5 cohorts; all patients receive 4 doses of C4-V3. Cohort 1 receives C4-V3 alone; once all 4 patients have received 2 doses and completed 6 weeks of treatment, toxicity data are reviewed. Barring serious adverse events, 4 additional patients are enrolled in Cohort 2 to receive C4-V3 plus a low dose (dose level 1) of IL-12. Barring serious adverse events, 4 additional patients are enrolled in Cohort 3 to receive C4-V3 plus a higher dose (dose level 2) of IL-12. Barring serious adverse events, 4 additional patients are enrolled in Cohort 4 to receive C4-V3 plus a higher dose (dose level 3) of IL-12. Barring serious adverse events, 4 patients are enrolled in Cohort 5 to receive C4-V3 plus a higher dose (dose level 4) of IL-12.\] Patients are followed for safety evaluations and changes in viral load through Week 48. If toxicity related to C4-V3 or IL-12 persists through Week 48, the affected patients are followed until resolution of the toxicity.