A phenomenon dubbed “repliclones” may help explain unsuppressed viral loads in PLWH who take their medications and whose virus is not resistant to their current drug regimen, a small study published in The Journal of Clinical Investigation found.
Researchers sequenced HIV from eight individuals who had been previously virally suppressed, were adherent to their HIV medications, and were not resistant to their current antiretroviral regimen. They found identical viral RNA sequences that didn’t change over time in the plasma of each participant—an indication that these were clones of HIV-1-infected cells, rather than virus spreading between cells (which would have led to some mutations). In half of the samples, the virus could reproduce.
The clone clusters were quite large (50 million to 350 million cells), but still comprised a small fraction of infected cells.
This discovery raises some questions, such as: How and why do these repliclones develop? How many people are affected? What does this mean for HIV care?
One thing is clear, however: If repliclones are the underlying cause of a person’s lack of viral suppression, changing that person’s drug regimen or providing additional adherence counseling will have no effect. This means patients who are viremic despite antiretroviral treatment adherence and no resistance mutations would require close monitoring rather than having their regimen changed, study author John Mellors, M.D., counseled in a press release.
The findings could also complicate HIV cure research, since these sets of cloned cells may represent a previously unappreciated viral reservoir that needs to be addressed for a “shock and kill” strategy to work.