Scientists See Promising Leads in Battle Against HIV

Pew’s biomedical scholars program alumni work to unravel how the virus survives—and how to defeat it

Scientists See Promising Leads in Battle Against HIV
Biomedical Scholars
Researchers aim to exploit some of HIV’s defense mechanisms to create more effective treatments.
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The first day of December marks the 30th anniversary of World AIDS Day, a chance for individuals, organizations, and governments to highlight efforts to eradicate the disease, support people living with HIV, and commemorate those who have lost their lives to the illness.

Over three decades, Pew biomedical scholars, health advocates, medical professionals, and other researchers have worked to improve HIV diagnosis and treatment and to prevent the virus’ spread. They have made important progress: For example, lifesaving drug therapies allow some people who are HIV positive to avoid the lethal later stages of the infection, known as acquired immunodeficiency syndrome or AIDS.

But the global fight is far from won, and alumni of the Pew scholars program are focused on scientific discoveries that could lead to a cure.

Part of their challenge is that HIV, like other pathogens, evolves new defenses. The virus hijacks the human immune system’s T-cells and uses them as factories to produce copies of itself. Scientists have seen, however, that the viral assembly line in a group of infected cells sometimes stops. Current drug therapies have little effect on HIV in this inactive state, and the virus can resume its attack on the body months or even years later from these latent reservoirs.

In his earlier work, Leor S. Weinberger, a virologist and 2008 Pew scholar, found evidence that this is a deliberate survival tactic. Weinberger and his group at the University of California, San Francisco have since investigated how HIV pulls off this feat. In the June 2018 issue of Cell, they explained that the virus uses a unique form of alternative splicing—a process that allows it to create a repertoire of proteins from a single gene. Notably, this form of splicing interferes with the normal fluctuation of genes that get turned into ribonucleic acid and proteins in T-cells, resulting in some that actively produce HIV and others that don’t. That allows the virus to essentially hide from drugs targeting it. Weinberger’s group sees potential to turn HIV’s splicing process against the virus to permanently lock it in a dormant state.

In another promising development, Katherine A. Jones, a 1987 Pew scholar, and her group at the Salk Institute for Biological Studies in La Jolla, California, may have identified a way to prevent latent HIV cells from reactivating, a discovery they reported in the May 2018 issue of PLOS Pathogens. Jones and colleagues found a drug compound that binds to and inhibits two proteins key to HIV’s reactivation. Currently, the compound is too toxic for human use, but Jones’ team thinks modifications will remove that problem.

Researchers are also working to reduce barriers to and problems with HIV treatment. Current therapies often have side effects for patients and can lose effectiveness as the virus builds resistance to a drug. Existing therapeutic regimens also require daily drug doses, a factor that can hinder treatment in parts of the world where patients lack reliable access to medications and health care providers.

Work by Pamela J. Bjorkman, a 1989 Pew scholar and 2017 Pew Innovation Fund Investigator, could help alleviate such obstacles. She studies how the immune system responds to HIV by looking at the structure of the pathogen’s proteins. In research led by Michel Nussenzweig, a former adviser to the Pew Latin American fellows program, Bjorkman and others have been developing antibodies to neutralize HIV. In September, this group wrote in the journal Nature about results of early clinical trials that show a combination of two new antibodies, administered by infusions once every three weeks, effectively suppressed the virus and was well tolerated by patients.

Separate work by Bjorkman’s team revealed new information on the structure of HIV proteins important to the virus’ fusion with the membrane of T-cells. The findings, published in the October 2018 issue of Cell Host & Microbe,could help scientists find new ways to design antibodies that disrupt HIV’s entry into host cells.

The need for HIV research remains as urgent as ever. Advances such as these are instrumental in defeating a virus as complex, agile, and deadly as HIV, and on this 30th World AIDS Day, they are but a few of the signs of hope for the millions of people living with HIV and their loved ones.

Kara Coleman directs The Pew Charitable Trusts’ biomedical programs, including the biomedical scholars, Pew-Stewart Scholars for Cancer Research, and Latin American fellows programs. 

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