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Ronald C. DeRosier, University of Miami

(CONVERSATION) Antiretroviral therapy has had a huge impact on the treatment of HIV infection worldwide. The millions of people who are currently taking these treatments under medical supervision can reasonably be expected to reduce their viral load imperceptible levels, eliminate the risk of transmission and live a normal life expectancy. However, antiretroviral therapy is not without drawbacks. People must take these medications regularly throughout their lives, and low compliance can lead to drug resistance.

A promising new option is on the horizon. I a a researcher studying AIDS treatmentsand I believe it monoclonal antibodies can be a game changer in HIV treatment.

HIV creates problems for antibodies

Antibodies these are proteins that serve as key players in the immune system’s response to disease-causing pathogens and allergens that cause allergic reactions. Antibodies recognize specific markers, or antigens, on potentially harmful substances and help the body eliminate them.

Over the past few decades, researchers have been able to isolate individual antibodies specific to the particular pathogen or allergen they are meant to attack. With this advance, monoclonal antibodies made in the laboratory became a a major segment of the pharmaceutical industry. You can see many ads on television or in magazines promoting monoclonal antibodies for the treatment of osteoporosis, autoimmune diseases, and various cancers.

Antibodies can also be used to treat viral infections, including COVID-19. But using antibodies gets more complicated with HIV, the virus that causes AIDS in humans.

One reason is that HIV has a huge number of options spread worldwide and even in one infected person. In fact, the genetic variation of HIV in a single patient exceeds the genetic variation of all the flu strains that circulate throughout the world during the entire flu season.

The immune system of an HIV-infected person creates antibodies to neutralize the virus. However, because these antibodies usually only recognize one particular strain, they are unable to neutralize other strains of HIV circulating in the population. In addition, HIV can mutate inside an infected person and avoid antibodies specific to the variant causing the original infection.

This ability to mutate and evade ongoing immune responses is a critical factor in the virus’s ability to reproduce continuously, a hallmark of AIDS. It also complicates the development of antibody treatments, which may account for the enormous genetic variability of HIV.

Broadly neutralizing antibodies show promise

The discovery of rare people who produce antibodies against HIV that can be effective against up to 80% of circulating strainshowever, has raised the prospect of anti-HIV antibody treatment.

These broadly neutralizing antibodiesor bnAbs, gave impressive results. A monkeyresearch found that a single administration of bnAbs could prevent infection with SHIV, the primate version of HIV. One study found that two broadly neutralizing antibodies were able to reduce the viral load to an undetectable level in infected monkeys.

In people, one administration study two bnAbs suppression of HIV replication and virtually undetectable viral load were also observed. one an early phase clinical trial in 2021 showed that a single bnAb could potentially offer protection against HIV infection.

Prolonged production of antibodies

All of the monkey and human studies mentioned above required re-administration of broadly neutralizing antibodies approximately every three weeks to maintain effective concentrations. This faces the same problem that antiretroviral therapies face, in that a person needs to take the drug frequently throughout their life. But researchers have found a potential solution.

The use of a small virus that does not cause disease is called an adeno-associated virus, to deliver broadly neutralizing antibodies to the body, can stimulate muscle cells to continuously produce these antibodies. Because muscle cells have a long life expectancy and can last an average of 10 to 16 years, they can be turned into factories that produce antibodies for virtually a lifetime.

One study that my colleagues and I did using adeno-associated virus showed that one monkey was able to produce these antibodies to more than six years after one injection.

Another monkey that the researchers named “Miami Monkey” is considered functionally cured, meaning that his viral load has been at an undetectable level for extended periods even without continuous antiviral therapy. Two other monkeys were also cured of AIDS using this approach.

Adeno-associated viral vectors for HIV antibody therapy still face another hurdle: anti-drug antibodies, or antibodies that the body produces in response to antibodies during treatment. Drug antibodies can occur when the body registers the antibody treatment as foreign and mounts an immune response against it, rejecting the treatment. They also caused problems with antibody treatment cancer and autoimmune disorders. This may be particularly true of broadly neutralizing antibodies that have unusual structures that deviate from the normal appearance of antibodies.

Researchers are working hard to develop simple and affordable approaches to help patients develop tolerance to broadly neutralizing antibodies. Some of these approaches include delivering treatment to other areas that have greater immune tolerance than muscle, e.g. to the liver and through the mouth.

Stay tuned for updates.

This article is republished from The Conversation under a Creative Commons license. Read the original article here: https://theconversation.com/hiv-therapies-currently-need-to-be-taken-regularly-for-life-longer-lasting-antibody-treatments-could-one-day-offer-an-equally-effective- disposable alternative-189867.

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