Nef gene function and HIV subtype influence viral reservoir size

In patients with human immunodeficiency virus (HIV), the size of the viral reservoir depends, at least in part, on their HIV subtype and the level of Nef gene activity, researchers say.

Although current HIV therapies can suppress the virus and prevent transmission to sexual partners, they are not yet able to eliminate the HIV reservoir of latently infected cells that re-establish infection once an individual stops therapy. As individuals with smaller latent HIV reservoirs should be more amenable to cure, remission, or post-treatment virologic control, Dr. Zabrina Brumme of Simon Fraser University in Burnaby, British Columbia, and colleagues studied the clinical, immunologic, and other determinants of reservoir size.

“Our findings are novel and important because they provide the first direct evidence that properties intrinsic to the infecting HIV strain-in particular, the subtype of the infecting viral strain, as well as the function of the key viral protein Nef, which is determined by the viral gene sequence-influence the size of the reservoir,” Dr. Brumme told Reuters Health by email.

“Our findings have no immediate clinical implications,” she noted. “It is early days in HIV cure research and we have a long way to go. Rather, our study, like many ongoing in the HIV cure research field right now, brings us incrementally closer to understanding the latent HIV reservoir-information that will help us, one day, develop a cure.”

Dr. Brumme and colleagues performed a post-hoc analysis of 30 Canadians ages 22-59 with recently (<6 months) acquired HIV who participated in a year-long study of combination antiretroviral therapy. Twenty-five (83%) of participants harbored HIV subtype B, which had previously been found to be associated with larger HIV reservoirs.