The study is the result of the collaboration between scientists at the Institut de Genetique Moleculaire de Montpellier, Universite Montpellier I & II, Montpellier, France, the Centre Hospitalier Universitaire Vaudois (CHUV) and at the Swiss Vaccine Research Institute, University of Lausanne, Lausanne, Switzerland.
The STEP HIV vaccine trial, which evaluated an adenovirus vector-based vaccine and enrolled 3,000 high-risk HIV seronegative subjects, was prematurely terminated last year. The primary objectives of the study were to determine the effects of the vaccine on i) the reduction of the acquisition of HIV infection, and ii) the reduction of the HIV viremia. STEP was stopped due to a lack of efficacy and a 2-fold increase in the incidence of HIV acquisition among vaccinated recipients previously exposed to the wild type adenovirus and therefore with high levels in the serum of antibodies against the vector.
Several hypotheses have been proposed to explain the increased acquisition of HIV infection and a number of strategies have been developed to tackle this issue. Most of the investigations have been focused on mechanisms of activation of CD4 T- lymphocytes, the primary target for HIV. These investigations have failed to generate a clear model to explain the increased incidence of HIV infection among vaccine recipients with high levels of adenovirus antibodies in the serum.