Ho has spent decades researching the pathogenesis of HIV infection, in particular the dynamics of HIV replication, and his work has led to the development of life-prolonging combination antiretroviral therapy. Currently, his group focuses on developing vaccines as well as other innovative prevention strategies. As head of the China AIDS Initiative, Ho seeks to comprehensively address the HIV/AIDS crisis in that country.
The Ho lab has been actively engaged in AIDS research for 36 years and has published more than 400 papers on the subject. The lab’s work helped pioneer the field of HIV quantitation in infected people. In the last decade, his research team extended this work and revolutionized the paradigm for AIDS pathogenesis by demonstrating the highly dynamic nature of HIV replication in vivo. Their elegant studies on HIV dynamics formed the foundation for combination antiretroviral therapy, which Ho also helped to champion. Such a treatment approach has transformed a death sentence to a manageable disease and is now being applied widely throughout the developing world.
A major focus of the Ho lab today is the design and testing of candidate vaccines to induce immune responses that could block HIV transmission. The team is currently pursuing multiple vaccine strategies, and manipulating the viral envelope glycoprotein to determine whether neutralizing antibodies could be induced.
Under a Vaccine Discovery Center grant from the Bill and Melinda Gates Foundation, Ho’s latest focus is a unique approach to HIV prevention. He and his colleagues are studying the passive administration of a humanized monoclonal antibody, known as ibalizumab, that potently and broadly blocks HIV infection by binding to domain 2 of human CD4, the principal receptor for HIV. Ibalizumab is being tested in clinical studies in HIV-infected individuals, showing a good safety profile and a well-documented antiviral effect, and is also being studied as a prophylactic in uninfected subjects. In addition, the lab has constructed second-generation forms of this antibody that offer improved antiviral potency and breadth, and enhanced pharmacokinetic properties.
Moreover, many bispecific antibodies have been constructed and tested, several of which have unprecedented breadth and potency against HIV. Ho’s group is also pursuing the use of gene transfer methods to express in vivo antibodies that might be of use in HIV prevention.
In addition, Ho and colleagues are actively studying long-acting antiretroviral drugs that are promising as prophylactics against HIV.