Could A Newly Identified HIV Reservoir Be the Key to an HIV Cure?

Study provides first direct evidence of HIV persistence in tissue macrophages in vivo, which could lead to a cure for HIV.

For the first time, scientists provided direct evidence of a new HIV reservoir that may serve as an additional target for HIV cure research.

In a study published in Nature Medicine, investigators found that HIV persists in HIV-infected tissue macrophages in vivo.

“These results are paradigm changing because they demonstrate that cells other than T cells can serve as a reservoir for HIV,” said lead author Jenna Honeycutt, PhD. “The fact that HIV-infected macrophages can persist means that any possible therapeutic intervention to eradicate HIV might have to target 2 very different types of cells.”

Despite the efficacy of antiretroviral therapy (ART) in managing HIV, the virus persists in T cells and is never eradicated. This is because the virus infects multiple cell types that could contribute individually to HIV persistence.

Although tissue macrophages are known to be crucial contributors to HIV pathogenesis, their specific role in HIV persistence during long-term suppressive ART was not established.

For the study, investigators used humanized myeloid-only mice that were devoid of T cells. The findings showed that HIV-infected tissue macrophages were rapidly suppressed by ART, which was indicated by a rapid drop in plasma viral load and a significant decrease in levels of cell-associated viral DNA and RNA.

At 7 weeks after ART interruption, there was no viral rebound observed in the plasma of 67% of the ART-treated animals. Furthermore, there was no replication-competent virus that was rescued from the tissue macrophages obtained from the mice, according to the study.

Contrastingly, in approximately 33% of animals the investigators found a delayed viral rebound that was consistent with the persistent infection in tissue macrophages.

“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.