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New Developments in HIV: Animal Research Provides Important New Breakthroughs

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According to the Joint United Nations Programme on HIV/AIDS (UNAIDS), 39 million people worldwide were living with HIV as of 2022, and there were 1.3 million new infections in 2022 alone.

While there have been rare successes in eliminating the virus through bone marrow transplants, there is no cure for the infection. Antiretroviral drugs can keep the virus at bay and prevent it from progressing to AIDS, but despite improved treatment options, there were still 630,000 AIDS-related deaths in 2022.

Several new treatment approaches show promise as more effective and permanent solutions for HIV infection.

Can Gene Editing Eliminate HIV?

Researchers at the Lewis Katz School of Medicine at Temple University and the University of Nebraska Medical Center have been able to eliminate HIV infection in mice.

Using a dual gene-editing therapy aimed at both HIV-1, the virus responsible for AIDS, and CCR5, a protein on the surface of some immune cells that facilitates the access of the virus into cells, combined with long-acting antiretroviral medications, the team was able to permanently remove the virus from animal models, which would prevent future rebound infection.

In mouse models, the combination of the gene-editing approach with the administration of antiretrovirals was able to suppress the HIV-1 virus and eliminate its replication in 58% of infected animals, which showed no trace of the virus.

In humans, the elimination of the virus from the body would enable those infected with the virus to stop taking antiretrovirals. With current HIV treatment, patients must take antiretrovirals indefinitely, even if their viral load is undetectable. The team plans to begin testing the new treatment on non-human primates.

A Vaccine for HIV

A new HIV vaccine developed by researchers at Scripps Research has shown a promising ability to neutralize the virus in mouse models.

The vaccine works by mimicking HIV to enable the host’s immune system to wage an immune response without the danger of infection.

Based on the preclinical results, the National Institutes of Health (NIH) has agreed to sponsor a future clinical trial.

New Drugs for HIV

In addition to vaccines, researchers are also developing new treatment methods for HIV.

One such effort, from a team of researchers from Johns Hopkins University School of Medicine and the NCI Center for Cancer Research, is focused on neutral sphingomyelinase 2 (nSMase2), an enzyme that plays a role in forming the protective envelope around the HIV virus.

The goal of the study was to determine whether blocking nSMase2 could prevent the formation of infectious HIV particles or prevent the resurgence of the virus that occurs when people stop taking antiretroviral medications.

Using mice with a humanized immune system, the team blocked nSMase2 using a new compound and then monitored the spread of the HIV virus in the mice. The results showed that blocking nSMase2 prevented the formation of infectious HIV particles by disrupting the formation of the viral envelope, so the virus was unable to develop into its mature, infectious form.

Next, they divided the mice into two groups, treating one with regular antiretrovirals and the other with the new nSMase2-blocking compound. HIV viral load decreased in both groups, but when treatment was stopped, the viral load in the antiretroviral-treated mice quickly rebounded, while the mice treated with the nSMase2 blocker showed no viral rebound—in fact, the virus was undetected up to four weeks after the treatment was stopped.

The team is optimistic that the discovery may lead to new treatments for HIV.

An HIV Drug to Treat Dementia?

While some researchers are looking for new treatments for HIV, others are exploring new uses for existing HIV drugs.

Researchers from the University of Cambridge have found that maraviroc, an FDA-approved antiretroviral drug used to treat HIV infection, is able to help the brain clear out damaging proteins associated with dementia in mice models.

Maraviroc, sold under the brand names Selzentry in the United States and Celsentri in Europe, was shown to slow brain cell death and the progression of memory loss in mice genetically altered to develop either Huntington’s disease or another type of dementia characterized by a buildup of tau protein.

The buildup of tau proteins is associated with the death of healthy brain cells, with results in symptoms including confusion, memory loss, and mood swings. The researchers were able to identify a mechanism that prevents the brain from being able to clear these proteins and use maraviroc to reverse it. The team is hopeful that the treatment could have implications for humans.

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