Emma Hitt, PhD

July 26, 2011

July 26, 2011 (Rome, Italy) — Vacc-4x, a peptide-based therapeutic vaccine, appears to reduce the viral load in patients with HIV who have maintained a viral response after discontinuing antiretroviral therapy (ART) in the previous 6 months, according to the findings of a phase 2 randomized trial.

Maja Sommerfelt, PhD, senior vice president and chief scientific officer at Bionor Pharma ASA, Oslo, Norway, presented the findings during a late-breaking poster session here at the 6th International AIDS Society Conference on HIV Pathogenesis, Treatment and Prevention.

According to Dr. Sommerfelt and colleagues, Vacc-4x aims to improve and sustain immune responses to the HIV-1 core protein p24. "The rationale is based on observations that cell-mediated immune responses to Gag are associated with virus control and delayed disease progression," they write.

The researchers describe preliminary data from a study of 135 patients, designed to evaluate the ability of Vacc-4x to prolong ART-free periods. The study was conducted in 13 European and 5 American centers, and "represents one of the largest therapeutic HIV-1 vaccine clinical trials to date," they note.

Patients had a viral load below 50 copies/mL in the previous 6 months and a prestudy CD4 cell count of at least 400 × 106/L. Study participants were randomized to receive Vacc-4x (n = 92) or placebo (n = 43).

After 6 immunizations on ART over 28 weeks, treatment was interrupted for up to 24 weeks (until week 52). ART was restarted between weeks 28 and 52 if any patient's CD4 cell count fell below 350 × 106/L or dropped by at least 50% on 2 consecutive tests. Subjects also were required to restart ART if their viral load increased to more than 300,000 copies/mL on 3 consecutive tests taken within 2 weeks of each other.

No increase in adverse events was noted in the Vacc-4x group, compared with the placebo group. In all, 126 patients completed the study. No statistically significant difference was observed between the 2 groups in change in CD4 count or time to ART resumption during treatment interruption. However, there was a statistically significant treatment difference between the Vacc-4x and placebo groups for viral load among patients who achieved a 6-month ART-free period (P = .0023).

In addition, a post hoc analysis found a significant reduction in viral load from the pre-ART level (0.55 log; P = .0003) in the Vacc-4x group (n = 44) at week 52 (off ART), compared with a nonstatistically significant viral load reduction (0.08 log; P =.89) in the placebo group (n = 18).

"An important aspect of this study is that we are looking at immunogenicity through ELISPOT responses," Dr. Sommerfelt told Medscape Medical News. "In patients with ELISPOT-positive responses, the Vacc-4x group had a trend toward a lower viral load, compared to placebo, so there's a qualitative difference as well, and we are potentially improving control of the virus."

Dr. Sommerfelt cautioned that there is more work to do analyzing the data and to understand the next steps to take with this agent.

"This is a large, carefully conducted study," said independent commentator Frances M. Gotch, PhD, professor of immunology in the Department of Medicine, Chelsea and Westminster Hospital Campus, at Imperial College London, United Kingdom. "However, the main findings (apart from safety and lack of toxicity) appear to be that in patients who achieved a 6-month ART-free period, those who had been vaccinated had a greater reduction in viral load at the end of the treatment interruption, compared with placebo patients," she told Medscape Medical News. "We do not know whether this finding may have any long-term clinical relevance," she said.

"Many questions remain concerning the possibility of the true HIV-specific immune reconstitution during HIV treatment," Dr. Gotch said. "In the future, it will be important to understand which types of immune responses are most important and when during disease progression these would be most easily induced," she added.

The study was funded by Bionor Pharma. Dr. Sommerfelt is an employee of Bionor Pharma. Dr. Gotch has disclosed no relevant financial relationships.

6th International AIDS Society (IAS) Conference on HIV Pathogenesis, Treatment and Prevention: Abstract TULBPE028. Presented July 19, 2011.

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