Strengthening Interactions Between HIV Researchers and Non-HIV Virologists

This year’s Keystone meeting on HIV Pathogenesis, Therapy and Eradication, which takes place in Whistler, British Columbia from March 26-31, is held jointly with a meeting on Virus Entry, Replication and Pathogenesis, which includes discussion of many viruses other than HIV. The idea of this combination is to strengthen the interaction between HIV researchers and researchers who work on viruses other than HIV, said Michael Farzan, a virologist from Harvard Medical School and one of the organizers of the Virus Entry, Replication and Pathogenesis track. “I hope that what will happen is that more than usual, ideas from virology go to HIV virology, and ideas from HIV virology go to the more conventional virology,” Farzan said, “because HIV researchers frequently reinvent wheels that other virologists have done, but on the other hand HIV is also frequently ahead because [it is] the most studied virus.” 

Robert Siliciano, a professor of medicine at Johns Hopkins University School of Medicine, kicked off the meeting last night with a keynote address that introduced the HIV Pathogenesis, Therapy and Eradication track. He walked the audience through his recently developed model that can predict antiviral activity of three-drug combinations in highly active antiretroviral therapy (HAART). 

He also said that it should in principle be possible to develop “resistance proof” drug combinations for HAART. For HIV to develop resistance mutations to antiretroviral drugs (ARVs), he said, drugs need to be at an intermediate concentration: Low enough so that there is some viral replication, but high enough so that there is selective pressure to favor the evolution of a mutant. Often people on HAART go through such a window of intermediate drug concentrations when they don’t take their drugs as prescribed, and develop drug resistance as a result. 

However, Siliciano said, certain ARVs such as protease inhibitors have such steep dose response curves that even a slight increase in drug concentrations results in much stronger inhibition of HIV replication. As a result, if people on HAART don’t take such drugs strictly as prescribed, they pass through this intermediate drug concentration window—where resistance can develop—very quickly, which is why in such cases resistance should not develop. Siliciano said this should also protect them from developing resistance to other drugs they are taking that have less steep dose response curves. “The end result is that you can design a regimen for which in principle resistance is not possible,” he said, adding that currently, this is just a theory that still needs to be tested. 

Siliciano’s talk was followed by another keynote address by Stephen Harrison from Harvard Medical School, which introduced the Cell Biology of Virus Entry, Replication and Pathogenesis track of the meeting. Harrison gave examples of what is known about the way viruses such as flu and Dengue virus enter the cell and said that in principle, the mechanisms used by different enveloped viruses to enter cells are quite similar. 

Similarities between the way the flu virus and HIV enter cells show that it made sense to organize this year’s meeting as a joint conference between HIV virologists and researchers who study viruses other than HIV, said Alan Engelman from the Dana-Farber Cancer Institute who is one of the organizers of the Pathogenesis, Therapy and Eradication track of the meeting. “This is a perfect example of how studying a different type of virus at the mechanistic level in the long run can completely apply to the HIV system,” he said.