While there is currently no cure for the human immunodeficiency virus (HIV) virus , researchers believe they are heading towards it. HIV, which causes acquired immunodeficiency syndrome (AIDS), can be controlled with antiretroviral therapy (ART). ART is currently the only available form of HIV treatment.
In 2018, 37,832 people were diagnosed with HIV in the United States and approximately 1.7 million people worldwide became infected with HIV. HIV prevention tools, such as vaccines , are important in limiting the spread of HIV. However, there is still no vaccine that can prevent or cure infection with this virus, although scientists are working to create one .
In a 2009 study, an experimental HIV vaccine was found to be 31% effective. The National Institutes of Health is conducting two late multinational clinical trials to develop a preventive HIV vaccine that will hopefully work for different populations. Researchers at the University of Pittsburgh similarly began clinical trials of a vaccine to treat HIV infection after finding a treatment that targets HIV that lurks in cells and then kills it in 2019.
These advances are promising, but the problems posed by the virus have long hampered research efforts to find a cure or vaccine.
Researchers have spent time and money developing a cure for HIV and AIDS for more than 30 years. They are still working to understand HIV and AIDS.
Discovering a cure and vaccine for HIV requires a lot of research and commitment on the part of scientists. However, a 2013 study found that young scientists believe the HIV landscape is overcrowded and should focus their research elsewhere. Research in this area has not yet led to the search for a cure or vaccine, so more work is still needed in these studies.
The virus also presents several problems that explain why a cure or vaccine for HIV has not been developed.
HIV is a moving target because it replicates rapidly, making hundreds of new copies of the virus every day and mutating in the process. These mutations can lead to errors that make the virus resistant to ART. Because of this, some strains of the virus attack the human immune system more aggressively than other strains. This leads to constant viral evolution and genetic variability of the virus in populations and among humans.
For HIV-1, just one strain of HIV, there are 13 different subtypes and subtypes that are geographically related, with a 15-20% variation within a subtype and up to 35% variation between subtypes. The genetic diversity of HIV viruses makes it difficult to develop a vaccine that elicits immune responses that can provide protection against a wide variety of variants.
HIV also has the ability to hide in tissues throughout the body and bypass the immune system. HIV is usually found in the blood, where it can be detected with an HIV test . However, when the virus enters a proviral state , when the virus is dormant (inactive) and hiding, the body's immune system is not warned about this. In this state, the virus will insert its genetic material into the material of its host cells (living cells infected by the virus) and will replicate as host cells (living cells infected by the virus) replicate.
The virus can lie dormant for a long time, leading to a latent infection. The term " latent reservoirs " is used to describe host cells that are infected but not actively producing HIV. While ART can lower blood levels of HIV to undetectable levels, hidden reservoirs of HIV may still exist. When a latently infected cell is reactivated, the cell begins to produce HIV again. For this reason, ART cannot cure HIV infection.
So, when developing a drug, scientists are trying to target hidden reservoirs by following the concept of "kick and kill" (also called "shock and kill"): they want to remove the virus from its hiding place and kill it. The challenge is to find out which cells contain HIV.
Two types of HIV drugs are currently being developed that can eradicate reservoirs of HIV.
- Functional treatment : controls long-term HIV replication without treatment.
- Sterilizing agent: eliminates the virus.
Antigens , the part of the virus that triggers an immune response, work after CD4 helper cells, which are also known as helper T cells or T cells (white blood cells that fight infection). T cells are responsible for killing infected host cells and regulating the immune system. However, constant exposure to high levels of antigens on T cells during HIV infection can lead to a serious dysfunctional T cell condition called immune depletion.
It becomes incredibly difficult for the immune system to fight HIV infection when T cells are depleted. In the final stages of depletion, T cells will die. The loss of these protective cells leaves the immune system defenseless against HIV infection, leading to the development of AIDS.
Scientists are investigating the feasibility of developing a T-cell HIV vaccine to treat HIV infection, as data shows that T-cell-mediated cellular immunity can maintain long-term control of HIV without disease or transmission. A vaccine that stimulates T cells has the potential to help kill HIV-infected cells and reduce HIV levels in infected people. Unfortunately, a vaccine that induces T cell production can increase susceptibility to infection because some T cells are important reservoirs for HIV-infected cells. None of the T-cell vaccine concepts tested to date has demonstrated sufficient efficacy.
HIV has been cured in one person, Timothy Ray Brown, also known as the Berlin Patient. In 2006 he was diagnosed with acute myeloid leukemia. He lived with HIV for many years and treated it with medicine. After a long cycle of chemotherapy, he decided to undergo two bone marrow transplants from an HIV-resistant donor. Brown has recovered from leukemia and HIV.
However, other HIV patients who have received similar treatment have not been cured. Brown is a scientific anomaly, and researchers can't figure out what changed his situation. To date, he is the only person functionally cured of HIV.
Another case involves a Mississippi baby (nicknamed "Mississippi Baby") who was born with HIV. Doctors treated her and she was HIV free until her mother stopped giving her antiretroviral therapy, after which the HIV finally returned. Before the HIV test, the boy went 27 months without positive results. He is currently back on antiretroviral therapy and is likely to stay for life. Researchers are fascinated by his remission period. The case of the Mississippi baby gives doctors hope that early and aggressive therapy can control HIV.
These cases allowed researchers to understand what they might need to study to create an effective drug and vaccine. The theoretical 'kick and kill' strategy is a two-step strategy that has the potential to be a cure for HIV. By activating latent infection with drugs that reverse the latency period, HIV emerges from its hiding place. The reservoir cells are then destroyed by other cells of the immune system.
AIDS Research Foundation has developed a research plan called CURE, which identifies four key scientific questions that represent the main barriers to curing from HIV:
- Determination of the exact location of the viral reservoirs that are stored in the body.
- Understand how HIV persists in reservoirs
- Registering the amount of viruses in them
- Virus limitation
While the kick-and-kill method can remove the virus from its hiding place, researchers also need to find ways to eradicate the virus before it can mutate or create new reservoirs. A combination of treatments can be a drug to completely kill the virus and save the immune system.
Latency Reversal Agents
Histone deacetylase (HDAC) inhibitors are used in hematologic cancers as chemotherapeutic agents. The FDA has approved the anticancer drugs Zolinza (Vorinostat), Farydak (Panobinostat), and Istodax (Romidepsin) for use in patients with HIV. These HDAC inhibitors clear the latent reservoirs of HIV.
While this sounds promising, the drugs also dampen the body's immune response. Because the reservoirs are automatically renewed and extensive, treatment may be more successful when combined with other treatments. This method is undergoing clinical trials in the hope that it will lead to the complete eradication of HIV infection.
It was once thought possible to reverse immune depletion with HDAC inhibitors, but research has shown that antigens mutate and escape the drug, making this an unlikely solution.
Broadly neutralizing antibodies
A group of people (one in 300) infected with HIV have an undetectable HIV viral load without using ART or any other HIV drugs. These people, known as elite controllers , have a low risk of infection and a well-developed immune system. A class of antibodies called broadly neutralizing antibodies (BNabs), which kill different genetic types of HIV, are produced by elite controllers faster than ordinary people, which means that these antibodies are capable of destroying the broader network of HIV. By contrast, it will take the average person years to produce BNab, and by then HIV will already be hiding in hidden deposits.
Although elite controllers fight HIV faster, they are twice as likely to be hospitalized for non-HIV-related illnesses as non-elite controllers. While BNab's research may lead to a vaccine, more clinical trials are needed to assess the potential of these antibodies in treating HIV.
Immune agents can help attack and kill HIV after the virus emerges from reservoirs and hiding places. Moderna, a biotech company, is developing an HIV vaccine that has been tested in monkeys. The vaccine is designed to teach the body to recognize variants of HIV and to stimulate the production of virus-like particles (VLPs) in the body. A similar vaccine that has proven successful is the human papillomavirus vaccine , which also uses VLPs.
The antibiotic concanamycin A is another immune strategy that researchers are studying. A research team focused on a protein called Nef, which HIV uses to evade the body's immune system. Pleycomacrolide, or a class of antibiotics called concanamycin A, has been found to interfere with the action of Nef. Researchers believe that when combined with ART, this type of therapy can remove HIV from the body.
Get the word of drug information
Most HIV drug or vaccine research is currently done in vitro or in animals, or is in the early stages of clinical trials. The search for a definitive cure for HIV continues and new discoveries continue to emerge in scientific research. Currently, antiretroviral therapy is the only treatment available for people infected with HIV. Until a cure or vaccine for HIV is developed, prevention of HIV infection through safe methods, post-exposure therapy, and pre-exposure therapy, along with testing to identify active cases, it is still the only way to avoid contracting the virus.