315-W. Immunogenicity of Remune in Subjects with Established HIV Infection

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Session 50 Poster Session
Therapeutic Vaccine Studies
Session Time: 4:30-6:30 pm
Room 4E-F

315-W.

Immunogenicity of Remune in Subjects with Established HIV Infection
G. Robbins*, M. M. Addo, H. Troung, A. Rathod, K. Habeeb, N. Basgoz, B. Davis, H. Heller, B. Walker, and E. Rosenberg
Massachusetts Gen. Hosp. and Partners AIDS Res. Ctr., Boston

Background: Virus-specific CD4 T helper (Th) cells are believed to play a pivotal role in immune control of HIV infection, however this immune response is weak or absent in the majority of chronically infected persons. One potential therapeutic vaccine designed to restore HIV-specific Th cell function is Remune, an envelope deplete, inactivated Zairian isolate administered with incomplete Freud’s adjuvant (IFA). This pilot study was done to determine if Remune compared to IFA alone could induce measurable HIV-specific immune responses in subjects with established HIV infection.
Methods: This was an investigator-initiated, single center, double-blinded, placebo-controlled, randomized trial of Remune vs IFA. 10 subjects were enrolled and randomized to 5 injections of either Remune or IFA alone. Inclusion criteria: CD4 >250 prior to initiation of ART, HIV RNA <500 for >6 months on stable ART. Remune and IFA were given on weeks 0, 12, 24, 36, and 48. Immunologic assays were performed at weeks 0, 4, 12, 16, 24, 28, 36, 40, 48, and 52. HIV antigens studied in Th assays included: p24, soluble p24, gp160, and HIV immunogen. The primary endpoint was augmentation of HIV-specific Th cell responses as defined as a 5-fold increase in the stimulation index (SI) from baseline for at least 2 HIV antigens on at least 2 occasions. Secondary outcome measures included magnitude and breadth of cytotoxic T lymphocyte (CTL) response, and delayed hypersensitivity (DTH).
Results: 8 men and 2 women were enrolled. Average time of HIV infection was 6 years (3-17). Average CD4 cell count at enrollment was 700 (481-945). All subjects maintained an undetectable HIV RNA viral load (<400 copies) during the study. 5 out of 5 subjects receiving Remune developed significant proliferative responses, compared to none of the 4 evaluable IFA subjects (p = 0.008, Fischer’s Exact). As expected, no subjects developed responses to soluble gp160 antigen. There were no significant differences in the magnitude of CTL responses, number of epitopes recognized, or DTH.
Conclusion: Remune was able to induce significant HIV-specific CD4 proliferative responses in subjects with chronic HIV infection. However, no significant changes were observed in CTL responses while patients were effectively treated with HAART. Whether or not the immune responses induced by this vaccine will be effective in controlling viral replication once therapy is interrupted remains to be studied.