Here we will answer questions about the most important scientific achievements and future directions for the development of therapy for the treatment of HIV infection.
Prepared by: Bratislav Prokić, September 2022
Review: Dr. Jovana Milić,
Metabolic clinic for HIV in Modena, Italy
What is the future of HIV therapy?
Research is underway on long-acting antiretroviral drugs, broadly neutralizing antibodies, and a therapeutic vaccine. The main goal of these researches is to develop a long-acting therapy, which would not require daily use, and which could be less toxic and more cost-effective.
What are long-acting HIV drugs?
Unlike today’s antiretroviral drugs in the form of pills that must be dosed every day, long-acting drugs allow for less frequent administration (once every few months). Long-acting drugs are most often in the form of injections, but patch and implant forms are also being investigated.
How far have we come in the development of long-acting drugs for HIV?
The first long-acting HIV therapy has been approved in the US and the EU. These are injections that contain two antiretroviral drugs (cabotegravir and rilpivirine) and are given once every two months (in the EU). Phase II and III of other long-acting drugs studies are in progress.
What are HIV broadly neutralizing antibodies (bNAbs)?
These are antibodies that can prevent a wide range of HIV strains from infecting human cells.
How do HIV broadly neutralizing antibodies work?
In the context of treatment, bNAbs can act in three ways: 1) bind directly to HIV and prevent it from entering the cell, 2) bind to the HIV-infected cell to stimulate and facilitate the part of the immune system (cytotoxic T lymphocytes) that is in charge to kill cells, 3) bind to a key part of HIV to stimulate immune system cells in a vaccine-like manner, preparing the immune system for future encounters with the virus.
How far have we come in the development of HIV neutralizing antibodies (bNAbs)?
So far, clinical studies in people living with HIV have shown that infusions of certain antibodies can suppress the virus, but only to a certain extent, and that treatment with one type of antibody encourages the emergence of strains of the virus that are resistant to those antibodies – just like with antiretroviral drugs. It appears that eventual antibody therapy will require a combination of multiple antibodies or a combination with long-acting antiretroviral drugs.
What are therapeutic vaccines for HIV?
Unlike vaccines that would prevent infection, therapeutic vaccines would stimulate the immune system of people living with HIV to control the virus at an undetectable level and thus end or limit the need for further therapy, with possible periodic booster doses.
How far have we come in the development of therapeutic vaccines?
Previous attempts to create effective therapeutic vaccines against HIV have been unsuccessful. Further efforts will depend on advances in science to better understand the evolution of the virus and the immune responses that effectively suppress HIV, and on improving the potential of those responses.
What are the future directions for the development of antiretroviral drugs for daily use?
Studies of innovative antiretroviral drugs for daily use, which have unique mechanisms of action, are ongoing: nucleoside reverse transcriptase translocation inhibitor (NRTTI), maturation inhibitors (MI) and others. These drugs are likely to be effective against strains of HIV that are resistant to other types of drugs.
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