The collection of immune cells that are latently infected with HIV—meaning they are not producing new virus—which constitute the bulk of the viral reservoir, is largely established at the time an individual starts antiretrovirals (ARVs).


These findings were Published in Science Translational Medicine. The study was led by Ronald Swanstrom, PhD, of the University of North Carolina School of Medicine, and Carolyn Williamson, PhD, of the University of Cape Town. The paper’s authors also included members of the CAPRISA research team in South Africa.


The researchers analyzed genetic sequences of HIV from blood samples drawn from nine South African women in the CAPRISA 002 cohort over a period of several years prior to their initiation of ARV treatment as well as a number of years after that point. They found that an average of 71% of the women’s viral reservoirs consisted of HIV strains closely related to those circulating in their blood just before they started treatment.


“This comes as a big surprise,” Swanstrom, said in a press release. ”Our work suggests that if we could understand the reservoir-forming process better, we might be able to intervene at the start of treatment to reduce the majority of the reservoir that forms at this time."


Swanstrom also said the 71% figure “is a much higher proportion than you’d see if the reservoir formed continuously before treatment and was always long-lived. So either the [ARV] therapy indirectly induced the formation of much of the reservoir, or it stabilized a reservoir that until then had been turning over rapidly.”


A previous study published in the journal eLife in 2016 supported the finding from this new research. The authors of that paper analyzed the evolution of HIV DNA in the blood cells of people on ARVs and found that the genetic sequences of the strains seen in the reservoir were indeed similar to those replicating in the blood just before the individuals started treatment.


The authors of the new study hypothesized that starting ARVs quiets the immune system by suppressing HIV replication. This in turn raises the likelihood that CD4 cells will turn into the long-lived memory cells that are the backbone of the reservoir.


In theory, combining ARV treatment initiation with another drug that inhibits this transition of CD4 cells into the memory state might blunt the formation of the reservoir and ultimately open the door to curing the virus.


To read a press release about the study, click here.


To read the study abstract, click here.