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AIDS

Snapshots of Life: Finding Where HIV Hides

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HIV

Credit: Nadia Roan, University of California, San Francisco

Researchers have learned a tremendous amount about how the human immunodeficiency virus (HIV),  which causes AIDS, infects immune cells. Much of that information comes from studying immune cells in the bloodstream of HIV-positive people. Less detailed is the picture of how HIV interacts with immune cells inside the lymph nodes, where the virus can hide.

In this image of lymph tissue taken from the neck of a person with uncontrolled HIV infection, you can see areas where HIV is replicating (red) amid a sea of immune cells (blue dots). Areas of greatest HIV replication are associated with a high density of a subtype of human CD4 T-cells (yellow circles) that have been found to be especially susceptible to HIV infection.


Simplifying HIV Treatment: A Surprising New Lead

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CD4+ cells in the gut

Caption: PET/CT imaging reveals a surprisingly high concentration (yellow, light green) of key immune cells called CD4 T cells in the colon (left) of an SIV-infected animal that received antibody infusions along with antiviral treatment. Fewer immune cells were found in the small intestine (right), while the liver (lower left) shows a high level of non-specific signal (orange).
Credit: Byrareddy et al., Science (2016).

The surprising results of an animal study are raising hopes for a far simpler treatment regimen for people infected with the AIDS-causing human immunodeficiency virus (HIV). Currently, HIV-infected individuals can live a near normal life span if, every day, they take a complex combination of drugs called antiretroviral therapy (ART). The bad news is if they stop ART, the small amounts of HIV that still lurk in their bodies can bounce back and infect key immune cells, called CD4 T cells, resulting in life-threatening suppression of their immune systems.

Now, a study of rhesus macaques infected with a close relative of HIV, the simian immunodeficiency virus (SIV), suggests there might be a new therapeutic option that works by a mechanism that has researchers both excited and baffled [1]. By teaming ART with a designer antibody used to treat people with severe bowel disease, NIH-funded researchers report that they have been able to keep SIV in check in macaques for at least two years after ART is stopped. More research is needed to figure out exactly how the new strategy works, and whether it would also work for humans infected with HIV. However, the findings suggest there may be a way to achieve lasting remission from HIV without the risks, costs, and inconvenience associated with a daily regimen of drugs.


Global Effort to End AIDS Would Save Millions of Lives

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Prevent HIV AIDS

Scanning electromicrograph of an HIV-infected T cell/NIAID

Almost 37 million people around the world are now infected with human immunodeficiency virus (HIV), the virus that causes AIDS [1]. But many don’t know they are infected or lack access to medical care. Even though major strides have been made in treating the infection, less than half receive antiretroviral therapy (ART) that could prevent full-blown AIDS and reduce the likelihood of the virus being transmitted to other people. Now, a new report restores hope that an end to this very serious public health challenge could be within reach—but that will require a major boost in commitment and resources.

The study conducted by an NIH-funded research team evaluated the costs and expected life-saving returns associated with ambitious goals for HIV testing and treatment, the so-called 90-90-90 program, issued by the Joint United Nations Programme on HIV/AIDS (UNAIDS) in 2014 [2]. The new analysis, based on HIV disease progression and treatment data in South Africa, finds that those goals, though expensive to implement, can be achieved cost-effectively, potentially containing the AIDS epidemic and saving many millions of lives around the globe.


AIDS Vaccine Research: Better By Design?

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OD-GT8 60mer

Caption: eOD-GT8 60mer nanoparticle based on the engineered protein eOD-GT8. Yellow shows where eOD-GT8 binds antibodies; white is the protein surface outside the binding site; light blue indicates the sugars attached to the protein; dark blue is the nanoparticle core to which eOD-GT8 has been fused.
Credit: Sergey Menis and William Schief, The Scripps Research Institute

A while ago, I highlighted a promising new approach for designing a vaccine against the human immunodeficiency virus (HIV), the cause of AIDS. This strategy would “take the immune system to school” and teach it a series of lessons using several vaccine injections—each consisting of a different HIV proteins designed to push the immune system, step by step, toward the production of protective antibodies capable of fending off virtually all HIV strains. But a big unanswered question was whether most people actually possess the specific type of precursor immune cells that that can be taught to produce antibodies that kill HIV.

Now, we may have the answer [1]. In a study published in the journal Science, a research team, partly supported by NIH, found that the majority of people do indeed have these precursor cells. While the total number of these cells in each person may be low, this may be all that’s needed for the immune system to recognize a vaccine. Based in part on these findings, researchers plan to launch a Phase 1 clinical trial in human volunteers to see if their latest engineered protein can find these precursor cells and begin coaxing them through the complicated process of producing protective antibodies.


Toward an AIDS-Free Generation: Can Antibodies Help?

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Virus and antibody bound to virus

Caption: Left: Human Immunodeficiency Virus (HIV); Right: VRC01 antibody (blue and green) binding to HIV (grey and red). The VRC01-HIV binding (red) takes place where the virus attaches to primary immune cells.
Credits: C. Bickel, Science Translational Medicine; National Institute of Allergy and Infectious Diseases

This year, an estimated 50,000 Americans will learn they have been newly infected with the human immunodeficiency virus (HIV), which causes AIDS [1]. The good news is that if these people are diagnosed and receive antiretroviral therapy (ART) promptly, most will enjoy a near-normal lifespan.The bad news is that, barring any further research advances, they will have to take ART every day for the rest of their lives, a regimen that’s inconvenient and may cause unpleasant side effects. Clearly, a new generation of safe, effective, and longer-lasting treatments to keep HIV in check is very much needed.

That’s why I’m encouraged to see some early signs of progress emerging from a small, NIH-supported clinical trial of an HIV-neutralizing antibody. While the results need to be replicated in much larger studies, researchers discovered that a single infusion of the antibody reduced levels of HIV in the bloodstreams of several HIV-infected individuals by more than 10-fold [2]. Furthermore, the study found that this antibody—known as a broadly neutralizing antibody (bNAb) for its ability to defend against a wide range of HIV strains—is well tolerated and remained in the participants’ bloodstreams for weeks.


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