Background:  Cell-mediated immunity plays an important role in the effective control of HIV-1 replication during acute and chronic infections. MVA-BN, a safe viral vector, which is unable to replicate in human cells, has shown also in previous phase I/II studies potent ability to induce cell mediated immune response. Therefore, we performed a phase-II-trial in 77 HIV-1-infected patients to test immunogenicity and safety of the MVA vector expressing HIV-1-LAI nef.

Methods:  In this single blind, controlled, randomized, multicenter study, all subjects received 3 subcutaneous vaccinations of either 1x10⁸ MVA-BN, 1x10⁸ MVA-nef, or 5x10⁸ MVA-nef (n =25, 26, and 26, respectively) at week 0, 8, and 16. Unsolicited and solicited adverse events were captured, and patients were monitored for any cardiac signs and symptoms. Viral loads, as well as CD4/CD8 counts, were monitored closely. Antibody response against MVA was measured with ELISA. Patients that received all vaccinations and remained stable on HAART with HIV-1 RNA levels <50 copies/mL were offered a structured treatment interruption. During treatment interruption viral load, as well as CD4/CD8 counts were monitored closely.

Results:  MVA-Nef proved to be safe and well tolerated. All patients reported local reactions, most of which were mild to moderate although a few patients had systemic reactions. Of 77 subjects, 60 had received smallpox vaccination. All 77 subjects received 3 vaccinations; 37 of them interrupted HAART after the third vaccination (1x10⁸ MVA-BN vs 1x10⁸ MVA-nef vs 5x10⁸ MVA-nef; n = 9:13:15, respectively). All experienced a viral rebound after structured treatment interruption. During a 12-week period only 3 of 37 subjects restarted therapy. To date viral load data at week 12 post-treatment interruption have been collected from 22 patients demonstrating a better control of the viral load in the group vaccinated with high-dose MVA-Nef than the MVA BN-vaccinated control group (ANOVA). A full analysis of the viral load data for all patients will be presented at the conference. All patients developed a strong MVA-specific humoral immune response. The analysis of Nef-specific cellular immune responses is ongoing.

Conclusions:  The first preliminary results of this study confirm the promising data of a previous phase I trial, which demonstrated that in a subgroup of patients therapeutic immunization seem to contribute to a better control of viral load during structured treatment interruption. The ongoing immune analysis will allow correlating viral control to Nef-specific immune responses.