In a first, scientists have identified HIV reservoir cells where the virus can persist despite treatment, a finding that may pave the way for new therapies to effectively treat the disease.
HIV cure research to date has focused on clearing the virus from T cells, a type of white blood cell that is an essential part of the immune system, researchers said.
They found the virus persists in HIV-infected macrophages - large white blood cells found in tissues throughout the body including the liver, lung, bone marrow and brain.
"These results are paradigm changing because they demonstrate that cells other than T cells can serve as a reservoir for HIV," said Jenna Honeycutt of University of North Carolina in the US.
Researchers demonstrated the ability of tissue macrophages to support HIV replication in vivo in the total absence of human T cells.
However, how macrophages would respond to antiretroviral therapy (ART) and whether macrophages represented a reservoir for HIV after treatment were unknown.
Using a humanised myeloid-only mouse (MoM) model devoid of T cells, researchers showed that ART strongly suppresses HIV replication in tissue macrophages.
Yet when HIV treatment was interrupted, viral rebound was observed in one third of the animals. This is consistent with the establishment of persistent infection in tissue macrophages, researchers said.
"The fact that HIV-infected macrophages can persist means that any possible therapeutic intervention to eradicate HIV might have to target two very different types of cells," Honeycutt said.
"This is the first report demonstrating that tissue macrophages can be infected and that they respond to antiretroviral therapy," Honeycutt said.
"In addition, we show that productively infected macrophages can persist despite ART; and most importantly, that they can reinitiate and sustain infection upon therapy interruption even in the absence of T cells - the major target of HIV infection," she said.
The study was published in the journal Nature Medicine.
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