HIV may still be replicating in lymphoid tissue, even when it is undetectable in the blood of patients on antiretroviral drugs, scientists have found, paving the way for a new "path to a cure".
The findings provide a critical new perspective on how HIV persists in the body despite potent antiretroviral therapy, researchers said.
"We now have a path to a cure," said Dr Steven Wolinsky, from Northwestern University Feinberg School of Medicine.
"The challenge is to deliver drugs at clinically effective concentrations to where the virus continues to replicate within the patient," said Wolinsky.
Combinations of potent antiretroviral drugs quickly suppress HIV to undetectable levels in the bloodstream of most patients, but HIV persists in a viral reservoir within lymphoid tissue in the body.
The virus rapidly rebounds in the blood if patients stop their drugs. This suggests that long-lived latently infected cells and/or ongoing low levels of HIV replication maintain these viral reservoirs.
Up until now, most scientists believed the reservoir only contained long-lived infected cells in a resting state rather than newly infected cells for several reasons.
No one had seen viruses with the new genetic mutations that inevitably arise when HIV completes cycles of growth and most patients do not develop the drug resistance mutations which might seem likely, if HIV was growing in the presence of drugs, researchers said.
The team examined viral sequences in serial samples of cells from lymph nodes and blood from three HIV-infected patients from the University of Minnesota who had no detectable virus in their blood.
Scientists found that the viral reservoir was, in fact, constantly replenished by low-level virus replication in lymphoid tissue with infected cells then moving from these protected sanctuaries into the blood.
Since infected cells in drug-sanctuaries within lymphoid tissue can still produce new viruses, infect new target cells and replenish the viral reservoir, it has not been possible to purge the body of latently infected cells and eradicate the virus.
A mathematical model tracked the amount of virus and the number of infected cells as they grew and evolved in drug sanctuaries, then moved through the body.
The model explains how HIV can grow in drug sanctuaries in lymphoid tissue where antiretroviral drug concentrations are lower than in the blood, and why viruses with mutations that create high-level drug-resistance do not necessarily emerge.
The findings provide a new perspective on how HIV persists in the body despite potent antiretroviral therapy.
The study also explains why the development of drug resistance is not inevitable when virus growth occurs in a place where drug concentrations are very low.
The study was published in the journal Nature.
