A team of University of Washington researchers received a five-year, $4.3 million research project grant (R01) from the National Institutes of Health to identify genetic mutations involved in HIV drug resistance.

“Resistance of HIV is increasing steadily around the world and HIV treatment is entering a new era,” says Dr. Paul Drain, one of the study’s principal investigators and an assistant professor at the UW Schools of Public Health and Medicine.

Treatment for non-B HIV-1, the form of the virus most prevalent outside of the United States, has shifted toward newer and more potent drugs, such as Dolutegravir. While the drug has proven effective, especially against strains of HIV resistant to other drugs, the fast-evolving virus inevitably develops resistance to any new treatment. These new forms of drug resistance must be identified to provide optimal treatments for people living with the disease.

The grant will fund whole genome sequencing of HIV samples from around the world to identify the mutations that make the virus resistant to drugs such as Dolutegravir. Their research findings, which will be based on the outcomes of over 16,000 people receiving treatment for HIV, could upend the current standards for HIV drug resistance testing.

“If we don’t understand HIV resistance, then we can’t treat patients properly,” Dr. Drain says. Because HIV mutates so readily, a person with HIV will have multiple strains of the virus, each with different potentially drug-resistant mutations. Current practice is to declare a treatment ineffective if 20 percent of a person’s HIV viruses are resistant, but not all resistance-causing mutations are likely to affect treatment outcomes at that same frequency.

This study will more precisely determine how common a drug resistance-causing mutation must be for it to render the treatment ineffective and will also assess how different types of mutations may interact to affect overall patient outcomes.

“The long-term goal of this proposal is to provide data to enable the best practices for HIV-1 care across a range of resource-limited settings, including Africa and Asia,” Dr. Drain says. He hopes the research will also validate the importance of providing resistance testing earlier in the treatment process to improve patient outcomes and slow the evolution of drug-resistant HIV.

Dr. Drain is an assistant professor in global health and medicine and an adjunct professor in epidemiology. Co-principal investigators of the grant are Dr. Geoff Gottlieb, UW professor of medicine and adjunct professor of global health, and Dr. Lisa Frenkel, UW professor of pediatrics and laboratory medicine and adjunct professor of global health and medicine. Dr. Frenkel is also co-director of the Center for Global Infectious Disease Research at Seattle Children's Research Institute. Funding comes from the National Institute of Allergy and Infectious Disease.