Northwestern University Feinberg School of Medicine
A team of international researchers led by Northwestern University found that HIV is still replicating in lymphoid tissue, even when it is undetectable in the blood of patients on antiretroviral drugs.
The findings provide a critical new perspective on how HIV persists in the body despite potent antiretroviral therapy.
“We now have a path to a cure,” said corresponding author Steven Wolinsky, M.D., chief, division of medicine-infectious diseases, at Northwestern University Feinberg School of Medicine and a Northwestern Medicine physician. “The challenge is to deliver drugs at clinically effective concentrations to where the virus continues to replicate within the patient.”
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. First, no one had seen viruses with the new genetic mutations that inevitably arise when HIV completes cycles of growth. Second, most patients do not develop the drug resistance mutations which might seem likely, if HIV was growing in the presence of drugs.
Because 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.
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.
This new understanding highlights how important it is to deliver high concentrations of antiretroviral drugs to all locations in the body where HIV can grow. Drugs that penetrate the newly discovered sanctuaries will be a prerequisite to the elimination of the viral reservoir and, ultimately, a step toward a cure.
“The study is exciting because it really changes how we think about what is happening in treated patients,” said co-author Angela McLean, professor of mathematical biology at Oxford University, who supervised the mathematical modelling. “It helps explain why some strategies that tried to clear the reservoir have failed.”
(A Wellness Update is a magazine devoted to up-to-the minute information on health issues from physicians, major hospitals and clinics, universities and health care agencies across the U.S. Online at www.awellnessupdate.com.)