The HIV virus still replicates in lymphoid tissue even when it is undetectable in blood among patients taking antiretroviral therapies, according to researchers from Northwestern University. Findings from the study are published in Nature

“The challenge is to deliver drugs at clinically effective concentrations where the virus continues to replicate within the patient,” stated Dr. Steven Wolinsky, chief of infectious diseases at Northwestern’s Feinberg School of Medicine. Strong antiretroviral drugs suppress HIV to undetectable levels for most patients but the virus persists in a reservoir within lymphoid tissue. If patients stop taking their drugs, the virus quickly rebounds in the blood. Researchers suggest that these latently infected cells and/or continuing low levels of HIV replication sustain these reservoirs. 

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Most scientists assumed the viral reservoir only contained long-lived infected cells in a dormant state instead of newly infected cells. Reasons for this thought was because nobody had observed viruses with the new genetic mutations that arise when HIV completes growth cycles, and most patients do not develop drug resistance mutations that would be expected if HIV was growing during antiretroviral therapy. 

Study authors looked at viral sequences in serial samples of cells from lymph nodes and blood from 3 HIV-infected patients with undetectable virus in their blood. Their viral reservoir was constantly replenished by low-level virus replication in lymphoid tissue with infected cells, which were then migrating into the blood. Because the infected cells can still produce new viruses, infect new cells, and constantly replenish the reservoir, eradicating all the latently infected cells and viruses has not been possible. The team used a mathematical model to to track the amount of virus and infected cells that grew and turned into drug “sanctuaries.”

The findings show a new viewpoint on how HIV persists in the body even with strong antiretroviral therapy and why drug resistance is not evident when virus growth occurs in an area where drug concentrations are very low. Further, the new findings indicate the importance in delivering high concentrations of antiretroviral therapy to all locations where HIV can grow. 

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