HIV persistence despite antiretroviral treatment depends in part on which human genes the virus integrates, according to a new study by the University of Washington Schools of Public Health and Medicine, Seattle Children's Research Institute and the Fred Hutchinson Cancer Research Center.

Lead co-author Dr. Sherry McLaughlin, a senior scientist at Seattle Children's, developed the test to analyze where HIV integrates into human chromosomes. The team analyzed 532 infected cells and sequenced the human chromosome where each virus was inserted, called the integration site. Specimens were analyzed from three individuals at three time points over approximately a dozen years of anti-HIV treatment.

The researchers discovered that when HIV inserts into cancer genes, the human cells proliferate more than when inserted into other genes, with the proliferating cells forming clones of infected cells. The novel insights into the mechanisms that allow HIV to persist should not only help design better therapies, but may also improve our understanding as to why effective HIV treatment does not lead to a normal life expectancy, said senior author Dr. Lisa Frenkel, adjunct professor of Global Health at the School of Public Health.

Dr. Frenkel, also professor of Pediatrics and Laboratory Medicine at the UW and co-director of the Center for Global Infectious Disease Research at Seattle Children's, noted the findings were made possible by a large team, including participants who volunteered to be studied over nearly 15 years. The study appeared in the Aug. 1 issue of Science.

"The research brings us closer to understanding why HIV is such a long-lasting infection and may lead us to new avenues to cure HIV," said co-lead author Dr. Thor A. Wagner, an assistant professor at the University of Washington and Seattle Children's. Additional co-authors from the UW and Fred Hutchinson center were Drs. Paul T. Edlefsen, Kavita Garg, Charles Cheung, and James Mullins.