Providence Research Profiles: Dr. Zabrina Brumme

Dr. Zabrina Brumme, Laboratory Director of the BC Centre for Excellence in HIV/AIDS (BC-CfE), leads one of only two laboratories in Canada that perform specialized precision medicine tests to guide HIV treatments. Earlier this year, Dr. Brumme was inducted into the Canadian Academy of Health Sciences, one of the highest honours in the Canadian health sciences community, in recognition of her leadership in HIV clinical care and research.

Dr. Brumme received her Ph.D. in Experimental Medicine in 2006 from the University of British Columbia, completed her post-doctoral fellowship at the Ragon Institute of Massachusetts General Hospital (MGH), the Massachusetts Institute of Technology (MIT) and Harvard University. Dr. Brumme’s research program integrates molecular biology, epidemiology and computational approaches to study HIV genetic diversity and evolution with the goal of informing HIV vaccine and eradication strategies. Most recently, her laboratory has focused on characterizing the genetics and dynamics of the latent HIV reservoir - the cells or tissues in the body where the virus persists and replicates - with the goal of designing safe and effective strategies to develop a cure for HIV.

Delivering personalized medicine to guide HIV treatment

“Precision genetic medicine is when you use genetic information to make a decision regarding a person's treatment. Arguably, HIV was the first health condition for which precision genetic medicine was employed…but in this case, we use the virus' genetic information to identify which therapies would be optimally effective for that person,” says Dr. Brumme.

HIV is a genetically diverse retrovirus, both at an individual as well as a global level. After a person acquires an HIV infection, the transmitted "founder" virus replicates and rapidly mutates in the body, creating a genetically diverse population of viruses. If HIV is left untreated, this virus population continually evolves to adapt to changing selection pressures, including the person's immune responses to the virus. If suboptimal HIV treatment is initiated, the virus can also rapidly develop drug resistance mutations that will further compromise treatment effectiveness. Indeed, Dr. Brumme spent much of her early career studying how HIV mutates to avoid detection by human immune responses, and how it mutates to become resistant to HIV medications. The first area of research is directly relevant to HIV vaccine design, while the second underpins the BC-CfE laboratory's precision viral medicine testing service.

The BC-CfE laboratory's precision viral medicine testing serves nearly all provinces and territories in Canada. These tests determine the unique sequence of a person's HIV and analyse it for the presence of drug resistance mutations, generating a report that lists which HIV medications will be effective against that person's virus and which will not. Another test identifies the presence of a specific human genetic variant that can cause a dangerous hypersensitivity reaction to a specific HIV medication, so that this drug is not prescribed to individuals with this variant. Together, these tests have helped guide HIV treatment selection for Canadians living with HIV for more than 25 years.

Bringing a personalized medicine focus to HIV cure research

In the past ten years, Dr. Brumme has brought her personalized medicine approach to the challenge of curing HIV. The main reason that HIV cannot be cured is because HIV, like all retroviruses, integrates its genome into that of the host cell. While most of these cells die within a couple days of infection, a small proportion of them persist long-term, even during HIV therapy. These cells are called "HIV reservoirs" because they can reactivate to produce infectious HIV, years or even decades later. This is why HIV therapy must be maintained for life. Curing HIV will require eliminating these HIV reservoirs, which is not currently possible to do safely.

Dr. Brumme's team is characterizing the genetic diversity and evolutionary dynamics of the HIV reservoir. As mentioned above, if HIV is left untreated, the more genetically diverse the virus will become in the person's body, and the more HIV genetic diversity there will be in the HIV reservoir. Like her work in HIV immune escape and drug resistance, Dr. Brumme is studying HIV reservoir diversity at both the individual and global levels. By studying individual participants in detail, Dr. Brumme's lab is using genetic techniques to understand how HIV gets seeded into reservoir cells, where these cells persist in the body, how long they remain, and which specific reservoir cells are the first to ‘wake-up’ and produce virus if HIV treatment is stopped. At the global level, Dr. Brumme is working with colleagues around the world to adapt key molecular reservoir quantification assay to detect the diverse HIV strains circulating in Africa, bringing HIV cure research and technologies to these priority areas.

While there is still much work to be done, Dr. Brumme’s dedication to delivering HIV clinical care and advancing translational research generates hope towards improved HIV treatment, and the ultimate possibility of a successful cure. She is highly deserving of her appointment to the Canadian Academy of Health Sciences.