A Phase I, Limited-Center, Sequential Cohort Trial of HIV Vaccine (Polyvalent Peptide Vaccine C4-V3) in Conjunction With Interleukin-12 in Subjects With Maximal Suppression of HIV Replication and CD4 Count > 400 Cells/mm3

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.