HIV is still growing, even when undetectable in the blood

January 27, 2016, Northwestern University
HIV (yellow) infecting a human immune cell. Credit: Seth Pincus, Elizabeth Fischer and Austin Athman, National Institute of Allergy and Infectious Diseases, National Institutes of Health

A team of international scientists 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 Dr. Steven Wolinsky, chief of 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."

The paper will be published January 27 in the journal Nature.

Combinations of potent 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 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.

The team examined viral sequences in serial samples of cells from lymph nodes and blood from three HIV-infected patients from the University of Minnesota (U of M) who had no detectable virus in their blood. Scientists found that the viral reservoir was, in fact, constantly replenished by low-level virus replication in lymphoid tissue with infected cells then moving from these protected sanctuaries into the blood.

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.

A mathematical model tracked the amount of virus and the number of infected cells as they grew and evolved in drug sanctuaries, then moved through the body. The model explains how HIV can grow in drug sanctuaries in lymphoid tissue where antiretroviral drug concentrations are lower than in the blood, and why viruses with mutations that create high-level drug-resistance do not necessarily emerge.

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.

Most importantly, 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 towards 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."

Explore further: Targeting HIV 'reservoir' could be first step to understanding how to cure the disease

More information: Persistent HIV-1 replication maintains the tissue reservoir during therapy, DOI: 10.1038/nature16933

Related Stories

Targeting HIV 'reservoir' could be first step to understanding how to cure the disease

December 1, 2015
A new clinical trial will test whether it is possible to destroy hidden reservoirs of HIV virus that are a key obstacle to curing the disease.

Cellular pathway discovered that may re-energize immune cells to eliminate HIV

January 12, 2016
Researchers at the University of Hawai'i (UH) and Oregon Health Sciences University (OHSU) have revealed a novel new immune pathway that can be targeted to increase the immune system's ability to eliminate HIV, the virus ...

HIV antibody infusion safely suppresses virus in infected people

December 23, 2015
A single infusion of a powerful antibody called VRC01 can suppress the level of HIV in the blood of infected people who are not taking antiretroviral therapy (ART), scientists at the National Institutes of Health report in ...

Targeted alpha therapy's potential to eliminate HIV-infected cells

December 21, 2015
Targeted alpha therapy has the potential to selectively eliminate HIV infected cells from the central nervous system, according to a recent study co-authored by the JRC. The study shows that a specific human antibody labelled ...

Identification of drug combinations that reverse HIV-1 latency

March 30, 2015
There are almost 40 million people throughout the world living with HIV-1/AIDs. While current antiretroviral therapies are able to reduce the amount of virus in the blood, HIV remains present in a latent state within T cells. ...

Towards elimination of HIV reservoirs

November 5, 2015
Current antiretroviral therapy can keep HIV in check and prevent AIDS in the vast majority of treated patients. However, as it is unable to eliminate viral reservoirs and cure the infection, patients need to stay on the life-long ...

Recommended for you

HIV exports viral protein in cellular packages

February 15, 2018
HIV may be able to affect cells it can't directly infect by packaging a key protein within the host's cellular mail and sending it out into the body, according to a new study out of a University of North Carolina Lineberger ...

Can gene therapy be harnessed to fight the AIDS virus?

February 13, 2018
For more than a decade, the strongest AIDS drugs could not fully control Matt Chappell's HIV infection. Now his body controls it by itself, and researchers are trying to perfect the gene editing that made this possible.

Big data methods applied to the fitness landscape of the HIV envelope protein

February 7, 2018
Despite significant advances in medicine, there is still no effective vaccine for the human immunodeficiency virus (HIV), although recent hope has emerged through the discovery of antibodies capable of neutralizing diverse ...

Scientists report big improvements in HIV vaccine production

February 5, 2018
Research on HIV over the past decade has led to many promising ideas for vaccines to prevent infection by the AIDS virus, but very few candidate vaccines have been tested in clinical trials. One reason for this is the technical ...

Microbiome research refines HIV risk for women

January 25, 2018
Drawing from data collected for years by AIDS researchers in six African nations, scientists have pinpointed seven bacterial species whose presence in high concentrations may significantly increase the risk of HIV infection ...

Researchers find latent HIV reservoirs inherently resistant to elimination by CD8+ T-cells

January 22, 2018
The latest "kick-and-kill" research to eliminate the HIV virus uncovered a potential obstacle in finding a cure. A recent study by researchers at the George Washington University (GW) found that latent HIV reservoirs show ...

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.