Grant: Operating Grant

At the end of 2002, an estimated 56 000 people in Canada were living with human immunodeficiency virus (HIV) infection; this is an increase from the estimated 48 900 in 1999. Despite of 8 years of extensive practice of the highly active antiretroviral therapy (HAART), which can suppress viral load and reduce both morbidity and mortality of AIDS patients, the number of deaths associated with HIV infection in USA was reduced by 64 % (45 765 to16 371). The emergence of resistant viruses and lack of patient compliance stemming from severe adverse side effects have resulted in many therapeutic failures. Therefore, recent efforts have begun to concentrate on development of antiviral drugs that target other processes in the virus life cycle, such as the entry process. The first HIV entry inhibitor, Fuzeon, was approved last year by FDA and other classes of entry inhibitors are under clinical development. It can be proposed that the overall efficacy of HIV entry inhibitors might be reduced by cellular factors that can promote virus adhesion onto target cells. Our recent data shows that the efficacy of the entry inhibitors is severely compromised in the presence of galectin-1, an endogenous lectin with affinity for beta-galactoside-containing oligosaccharides. Therefore, we propose to test several galectin-1 inhibitor candidates in order to use them as "sensitizers" of HIV entry process for the efficient treatment with the entry inhibitors.