Acquired immunodeficiency syndrome or AIDS is the deadliest disease caused by human immunodeficiency virus or HIV. Since its first documentation in 1981, HIV/AIDS has become the most persistent pandemic condition, despite having groundbreaking advancement in treatment strategies.
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What is HIV?
HIV is a virus that attacks and destroys a particular type of white blood cell called CD4+ T cells, which play an immensely important role in fighting against infections. This impairment in the immune system leads to the development of severe opportunistic infections and even cancer.
The virus is transmitted through certain body fluids of an infected person, especially semen, blood, and breast milk. Without treatment, people with acute HIV infection can gradually progress toward the development of AIDS, which is the most advanced and lethal stage of HIV infection.
What is the general treatment for HIV?
Although there is no complete cure for HIV yet, the condition can be effectively controlled by appropriate treatment. People suffering from HIV are treated with antiretroviral therapy (ART), which is very effective in reducing the amount of virus in the blood to an undetectable level.
People who follow ART exactly as prescribed can achieve an undetected virus load and continue to live a healthy life without any risk of sexually transmitting the virus to their partners.
For HIV-negative people, pre-exposure prophylaxis and post-exposure prophylaxis medicines are considered very effective in preventing possible HIV transmission.
What are the recent advancements in HIV treatment?
Given the significant improvement in HIV management by ART, today’s research mainly aims at developing antiretroviral medicines with long-lasting effects. Unlike currently available drugs with daily dosing, the future long-lasting drugs are expected to have weekly, monthly, or even less frequent dosing.
The long-lasting ART can be of different formulations, including pills, injections, patches, or implants. Also, to have fewer side-effects, such formulations are expected to improve treatment adherence and reduce treatment-related costs.
Another important approach is to develop broadly neutralizing antibodies that can facilitate HIV treatment in many ways. These antibodies can directly bind to the virus and prevent their entry to the cells; thus, increasing the rate of virus elimination.
In addition, they can trigger an immune response in HIV-infected cells to ensure the killing of the virus. Most importantly, the antibody by binding to a key viral fragment can form a complex that can initiate an immune response similar to a vaccination, which subsequently will help develop immunity against future viral encounters.
Similar to ART that includes a combination of drugs, an antibody-based treatment should include a combination of multiple antibodies or a combination of drugs and antibodies. Studies conducted on monkeys have shown that a combination of complementary antibodies can effectively suppress HIV infection for a prolonged period.
Although no vaccine is still available to prevent HIV infection, the development of therapeutic vaccines that can be given to already infected people is going on. By stimulating the immune system, these vaccines will prepare the body to gain control over HIV infection for a prolonged period.
Also, the development of new drugs for the usual daily ART is going on. Some drugs that are under investigation include nucleoside reverse transcriptase translocation inhibitors (inhibit HIV reverse transcriptase and prevent DNA synthesis) and maturation inhibitors (halt viral maturation by targeting HIV lifecycle).
Moreover, drugs that bind to viral surface protein (gp120) to inhibit virus-mediated immune cell infection, as well as drugs that inhibit capsid (protein shell to cover viral genome) formation are under investigation.
Is there any HIV cure in development?
Several attempts have been taken for developing a permanent cure for HIV. Of them, the most potential one is the development of drugs that can inhibit viral replication by binding to a specific RNA sequence of the virus. The main goal of this approach is to target the HIV reservoir that remains in a dormant form inside the cells.
Another important method is to develop drugs that can activate the dormant viral reservoir first, followed by the killing of the virus by the usual ART. Similarly, a double vaccine approach has been developed, wherein one vaccine targets the reservoir, while the other triggers the synthesis of antibodies that inhibit viral replication.
However, the currently available drugs are capable of activating only 5% of the viral reservoir, which is the major drawback of this approach.
HIV immunotherapy is another vital approach that includes drug-mediated activation of the viral reservoir and vaccine-mediated induction of HIV-specific robust immune response. In this context, the most potential vaccine is the one that triggers antibody production against the HIV protein 3S, which prime T cells to recognize and kill the virus in a more effective way.
Gene editing is another potential approach that introduces a specific mutation in the human genome, which makes them resistant to HIV infection. About 1% of the world population who are naturally immune to HIV possess this mutation.
This genetic mutation causes the development of an immune cell surface protein (CCR5) that is structurally different from the wildtype protein. The virus cannot bind the altered protein; as a result, it becomes impossible for the virus to enter the immune cell and infect it.
In the future, such mutations can be introduced in a much easier way through the CRISPR-Cas9 gene-editing tool.
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