HIV hides and grows inside the body even when undetectable in blood

HIV can hide and grow in body ‘sanctuaries’ after disappearing from blood, study says

Researchers pinpoint how HIV hides and grows inside the body even when undetectable in blood

HIV continues to replicate in the body even if it’s undetectable in the blood after antiretroviral treatment, scientists have discovered.

It explains how the virus rapidly bounces back – and keeps growing – after a patient stops taking antiretroviral drugs.

Study author Dr Steven Wolinsky, chief of infectious diseases at Northwestern’s Feinberg School of Medicine, said: ‘We now have a path to a cure.

‘The challenge is to deliver drugs at clinically effective concentrations to where the virus continues to replicate within the patient.’

Potent antiretroviral drugs are able to seemingly get rid of HIV from the bloodstream in most patients.

After the treatment, their blood tests may not detect the virus.

However, HIV is still growing in a viral reservoir within the lymphoid tissue in the body at that time.

And, it ‘quickly rebounds’ in the blood after patients stop taking the drugs.

Scientists concluded that latently infected cells or ongoing low levels of HIV replication maintain those viral reservoirs during antiretroviral treatment.

Scientists long believed that the reservoir only contained long-infected cells in a resting place – instead of newly infected cells.

That’s because none of them had seen viruses with new genetic mutations that arise when HIV completes its growth cycles.

Furthermore, most patients don’t develop drug resistant mutations – which would seem likely if HIV was growing in the presence of drugs.

The study analyzed viral sequences in serial samples of lymph node cells.

They also examined blood from three HIV-infected patients.

Each of those patients had no detectable virus in their blood.

The scientists determined that the viral reservoir was constantly replenished by low-level virus replication in the lymphoid tissue.

Infected cells would then move from those ‘protected sanctuaries’ and into the blood, they found.

Therefore, infected cells in drug-sanctuaries within the lymphoid tissue can still produce new viruses.

HOW HIV INFECTS

HIV infects CD4+ T-cells, which play a vital role in the immune system and protect us from diseases. As HIV progresses, it reduces the number of active T-cells in the body until the immune system cannot function correctly, a state known as 'acquired immune deficiency syndrome' or AIDS.

Current World Health Organisation guidelines, which the UK government follows, recommend only beginning HIV treatment when the number of T-cells in the bloodstream falls below a certain level.

However, the new model predicts that treatment should start as soon as possible after infection to prevent AIDS from developing in the long term.

They can also infect new target cells and replenish the viral reservoir.

That’s why drugs have not been able to completely purge the body of latently infected cells – and kill the virus all together.

The scientists utilized a mathematical model to track the amount of the virus and number of infected cells as they grew in the sanctuaries – and as they then moved through the body.

The model showed that HIV grows in areas where antiretroviral drug concentrations are lower than in the blood.

The scientists concluded that it is important to deliver high concentrations of antiretroviral drugs to all locations in the body where HIV may grow and evolve.

As such, drugs that penetrate these ‘newly discovered sanctuaries’ will be required to eliminate the viral reservoir – and may bring the medical community closer to finding a cure.

Co-author Dr Angela McLean, a professor of mathematical biology at Oxford University, said: ‘The study is exciting because it really changes how we think about what is happening in treated patients.

‘It helps explains why some strategies that tried to clear the reservoir have failed.’

The study was published in the journal Nature. 

A new study shows that HIV can still live and grow in the body even after disappearing from the blood following aggressive antiretroviral therapy.

The research, published in the journal Nature on Wednesday, involved looking at samples of cells from the lymph nodes of three patients who appeared to have cleared the virus. The researchers found that cells in the lymph node tissue can still produce new viruses and infect new target cells.

The groundbreaking idea of viral reservoirs of HIV made headlines in July 2014 when a Mississippi girl born with HIV, who was believed to be cured after early treatment, tested positive for the virus after stopping therapy. In her case, doctors think the infection reemerged from a viral reservoir that contained cells in a resting state that were not proliferating.

The latest study, funded by the US National Institutes of Health, appears to show a different type of “sanctuary,” as the researchers called it, that harbours cells with low levels of HIV replication that move into the blood. Researchers used a mathematical model to track the amount of virus and the amount of infected cells as they grew and moved through the body.

This suggests that virus growth could occur in a place where drug concentrations are very low.

“These findings are important as it is critical for the field of HIV cure research to know whether new infectious cycles are indeed continuing in patients on seemingly effective treatment,” said Deborah Persaud, a professor of infectious diseases at Johns Hopkins University School of Medicine.

But Persaud, who was not involved in the lymph node research but was part of a team caring for a baby who had received a treatment similar to the Mississippi child, said the study is limited by its small sample size and the fact that the analyses were done during the first six months of combination treatment “when the infected pools are still very dynamic.” She said a similar study on patients with longer-term treatment may offer more clues about what is going on.

Co-author Steven Wolinsky, chief of infectious diseases at Northwestern University Feinberg School of Medicine and a Northwestern Medicine physician, said in a statement that the research indicates that “the challenge is to deliver drugs at clinically effective concentrations to where the virus continues to replicate within the patient.”

Angela McLean, a professor of mathematical biology at Oxford University and who supervised the mathematical modeling, added that the study “really changes how we think about what is happening in treated patients.”

“It helps explain why some strategies that tried to clear the reservoir have failed,” she said.