“Science can change the world”

In the basis of continuous research effort there is a belief that a difficult current state can be changed by “Scientific Research”.

I have been engaged in the basic and clinical research of this infectious disease since 1984 when HIV-1 was isolated as a causative virus of AIDS in United States. I had taken charge of caring a lot of cases of HIV-1 infection from 1986 when I came back to Japan at that time notifying patients of HIV-1 infection was almost “condemnation to death”. A lot of young lives were lost to our regret including patients infected by the use of contaminated blood products. In 1997 advent of antiretroviral therapy (ART), which uses the combination of potent anti-retroviral agents, has resulted in a reduction in the rates of opportunistic infection, hospitalization, and mortality among HIV-infected patients after the research of the antiviral drug advanced. Recovery of the immunity was observed even for the cases of full-brown AIDS. “Final illness” became a chronic ailment that was able to be treated. Thus current treatment strategy using anti-retroviral agents that inhibit life cycle of HIV-1 replication had a major impact on HIV/AIDS medicine. However, ART is not free from problems of drug resistance and chronic toxicity like modulation of lipid/glucose metabolism during long-term continuous therapy. In addition, recent report suggested that despite suppressive ART active replication persists and drives immune activation and inflammation at abnormal levels. From this stand point life-long treatment is essential once the treatment initiated. Thus, the studies that clarify how the virus keeps persistent infection under such effective ART are the first priority research to develop a new treatment strategy that targets remaining virus infected cells. We have isolated a series of neutralizing monoclonal antibodies (MAbs) from the cases of long-term non-progressive disease without tART for a long-term. These MAbs have been used for an effective vaccine development. On the other hand, we also identified a small molecule that can induce structural changes in envelope trimer complex resulted in higher sensitive phenotype of the virus to neutralizing MAbs. In addition, we are currently constructing recombinant antibodies using genes from the antibody producing cells for the development of agents that attack the remaining HIV producing cells by ADCC.

The basic stance of my research is to contribute patients infected with HIV-1 by the research started from the patients, while taking charge of the treatment of the HIV-1 positive cases around 60. We are looking forward to hearing from younger doctors/student/researchers aware of prevailing conditions that can be changed by “Scientific Research”.

Shuzo Matsushita