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HomeEditor's PickLong-term suppression of HIV while pausing medication — NIH study

Long-term suppression of HIV while pausing medication — NIH study

Two people with HIV, who were able to stop taking medication for several years without becoming ill from the virus, offer clues for future strategies to suppress the infection, found an NIH study in Nature Medicine.

But both eventually had to restart taking medication, showing the current limitations of such approaches, says Tae-Wook Chun of the National Institutes of Health (NIH) in Maryland.

People with HIV can avoid becoming ill by taking lifelong medicines that stop the virus from multiplying, but copies of the virus remain in their immune memory cells throughout the body. This means that for most, if they stop medication, the virus starts multiplying again and levels in the blood rebound, requiring a return to drug therapy.

A few individuals who pause their HIV medication donʼt see their blood virus levels quickly rebound, but it is unclear why. They are sometimes called “post-treatment controllers”. The phenomenon seems to happen more often in people who begin anti-HIV drug treatment in the first few weeks after infection, perhaps because the virus doesnʼt have a chance to become established in so many of their immune cells.

The latest study, which was published in Nature Medicine, looks at two people who both began early anti-HIV treatment and later stopped their medication as part of an NIH trial of a therapeutic vaccine to treat HIV infections, although they received a placebo version of the vaccine. When the virus didnʼt restart multiplying at the end of the six-month trial, the men chose to stay off their medication and continue having frequent blood tests, even though they had been told they had the placebo.

They were able to continue without anti-HIV medication for 3.5 and four years, but different immune mechanisms seemed to be responsible in each case.

There are two main arms of the immune system: antibodies and T-cells. Until now, it was thought that T-cells, which directly kill virus-infected human cells, were more important for post-treatment controllers. But Chun and his colleagues found that while T-cells were responsible in one man, antibodies were suppressing virus multiplication in the other. “He had an amazing antibody response that probably completely contained viral replication,” says Chun.

This second man had to restart medication because he became infected with another HIV infection, which was resistant to his antibodies. HIV viruses are highly variable and there are many genetic subtypes circulating.

The first man, who was being protected by T-cells, saw three relatively small rises in the level of virus in his blood followed by spontaneous falls. After three years, he chose to restart medication without telling his doctors, which they discovered through a regular blood test.

The findings show that researchers looking at post-treatment controllers need to frequently test peopleʼs blood samples, both for new HIV infections and for evidence of HIV drugs even if they arenʼt being officially provided, says Chun.

“Any case of spontaneous control of HIV in the absence of [antiviral] therapy is worth being reported. It will add to the body of information we have,” says Javier Martínez-Picado at the IrsiCaixa AIDS Research Institute in Badalona, Spain.

Martínez-Picadoʼs team has been studying the only three people thought to have been cleared of an HIV infection, which happened because they developed cancer that needed a bone marrow transplant. They received bone marrow from people who had a natural mutation that gives their immune cells some resistance to the virus.

Study details

Distinct mechanisms of long-term virologic control in two HIV-infected individuals after treatment interruption of anti-retroviral therapy

Jana Blazkova, Feng Gao, Manukumar Honnayakanahalli Marichannegowda, J. Shawn Justement, Victoria Shi, Emily J. Whitehead, Rachel Schneck, Erin Huiting, Kathleen Gittens, Mackenzie Cottrell, Erika Benko, Colin Kovacs, Justin Lack, Michael Sneller, Susan Moir, Anthony Fauci & Tae-Wook Chun

Published in Nature Medicine 28 October 2021

Abstract
Certain infected individuals suppress human immunodeficiency virus (HIV) in the absence of anti-retroviral therapy (ART). Elucidating the underlying mechanism(s) is of high interest. Here we present two contrasting case reports of HIV-infected individuals who controlled plasma viremia for extended periods after undergoing analytical treatment interruption (ATI).

In Participant 04, who experienced viral blips and initiated undisclosed self-administration of suboptimal ART detected shortly before day 1,250, phylogenetic analyses of plasma HIV env sequences suggested continuous viral evolution and/or reactivation of pre-existing viral reservoirs over time. Antiviral CD8+ T cell activities were higher in Participant 04 than in Participant 30.

In contrast, Participant 30 exhibited potent plasma-IgG-mediated neutralization activity against autologous virus that became ineffective when he experienced sudden plasma viral rebound 1,434 d after ATI due to HIV superinfection. Our data provide insight into distinct mechanisms of post-treatment interruption control and highlight the importance of frequent monitoring of undisclosed use of ART and superinfection during the ATI phase.

 

New Scientist article – Two people suppressed HIV for years while pausing medication (Open access)

 

Nature Medicine abstract – Distinct mechanisms of long-term virologic control in two HIV-infected individuals after treatment interruption of anti-retroviral therapy (Open access)

 

See more from MedicalBrief archives:

 

ollowing Tx interruption, most children recover immunologically

 

Tests identify HIV's final redoubt

 

Powerful antibodies can completely suppress HIV for several months

 

 

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