One of the challenges to curing HIV is that the disease lurks in the body, even when it’s being treated with anti-retroviral medication. Now this puzzle is one step closer to being solved. An ongoing study  by a team of researchers at Oregon Health & Science University’s Vaccine & Gene Therapy Institute (VGTI) has identified a key biological barrier to the goal of curing HIV infection in people on anti-retroviral therapy. This work, published in Nature Medicine, builds on previous research by Louis Picker, M.D., associate director of VGTI. Picker’s lab uses a typically harmless virus called cytomegalovirus, which is already carried by a large percentage of the population, to target simian immunodeficiency virus, or SIV, a nonhuman primate form of HIV that causes AIDS in monkeys.

The latest breakthrough shows that even in nonhuman primates with highly effective immune (killer T cell) responses to the SIV–so-called “elite controllers”–the disease could still persistently replicate in B cell follicles, which exclude the antiviral killer cells. Thus, the virus found a biological sanctuary, where it could not be destroyed by even the most effective killer T cells. In SIV-positive monkeys on anti-retroviral medications, the low-level SIV replication that remained was largely found in the same B cell follicles, suggesting that therapeutic vaccines targeting killer T cells, which are designed to rid the body of this residual SIV, will fail until the B follicle sanctuary can be breached.

The researchers report that this discovery has identified one of several key barriers to eliminating SIV in nonhuman primates, barriers that also complicate development of a curative HIV therapy in humans. Another Picker lab report published in 2013 described a promising vaccine that was able clear SIV from the monkey’s body when given before infection. Picker’s group is currently testing whether this novel vaccine can facilitate of clearance of SIV when given after infection. The current findings help Picker and colleagues better understand the barriers needed to optimize this vaccine, with the hope that it will ultimately contribute to a cure for HIV.

This work was funded in part by the National Institutes of Health, National Institute of Allergy and Infectious Diseases grants 4R37A1054292 and 1U19AI096109.