There is currently no cure for HIV because the virus is able to persist in the body even during long-term antiretroviral therapy. BC-CfE scientists have published new research that characterizes in detail the HIV sequences that persist in the bodies of viremic controllers. Viremic controllers are a rare group of people whose immune systems naturally control HIV replication to low levels, but who nevertheless still benefit from antiretroviral therapy. This new research adds to the body of knowledge that is needed to develop an HIV cure.
The paper, titled HIV proviral burden, genetic diversity, and dynamics in viremic controllers who subsequently initiated suppressive antiretroviral therapy, was published in mBio, the premier open access journal of the American Society of Microbiology. BC-CfE researchers F. Harrison Omondi, who is also a PhD candidate at Simon Fraser University (SFU), and Hanwei Sudderuddin, who is also a MSc student at the University of British Columbia, co-led the study in collaboration with scientists at SFU and the BC-CfE.
Omondi and Sudderuddin characterized the genetic diversity of HIV sequences that persisted in the study participants, and how long each sequence had persisted in each individual. They were also interested in documenting differences in these metrics between individuals. It is important to study the characteristics of persisting HIV sequences because, in order to cure HIV, effective strategies will need to be developed to target and eliminate them. Studying these characteristics in many different groups of people will also ensure that an HIV cure strategy, once developed, will be applicable to all.
The two researchers focused on viremic controllers because they are understudied in HIV cure research. Whereas many researchers are studying HIV elite controllers, rare individuals whose immune systems suppress HIV replication to undetectable levels without antiretroviral therapy, much less attention has been paid to viremic controllers. Omondi and Sudderuddin hypothesized that since viremic controllers naturally control HIV replication prior to therapy, the amount and genetic diversity of HIV sequences that persisted during therapy would be limited. To their surprise, they observed substantial HIV diversity and, in some participants, quite large pools of persisting HIV sequences. With this information, the co-leads were also able to estimate the rate at which persisting HIV populations “turn over” in the body prior to therapy. They estimated this to occur at an average half-life of less than one year in most individuals, though in some people this rate is much slower.
HIV cure strategies will need to overcome within-host proviral diversity, even in individuals who naturally controlled HIV replication before therapy.
– The authors concluded
Their results also underscore the importance of early treatment, as this will limit reservoir diversity, which remains critical for those few people who naturally control their viral loads to low levels.
“One participant illustrated the importance of early treatment particularly well,” Dr. Zabrina Brumme, the BC-CfE’s Laboratory Director said of the study findings. “Initially, this person was a viremic controller, but later they lost control and their viral load increased dramatically. When this happened, the genetic diversity of their HIV also increased dramatically, as did the overall number of HIV sequences persisting in the body. Had this person initiated therapy earlier, their pool of persisting HIV sequences would have been much smaller and less genetically complex, and possibly easier to eliminate. The results of our study reveal that HIV cure strategies will need to overcome HIV diversity, even in individuals who naturally control HIV before starting therapy.”