Introduction to HIV
Human immunodeficiency virus (HIV) is a virus that causes defects in the human immune system. HIV destroys the body's T lymphocytes, thereby blocking the process of cellular immunity and humoral immunity, resulting in paralysis of the immune system, resulting in the spread of various diseases in the human body, eventually leading to acquired immunodeficiency syndrome (AIDS). The incubation period of HIV in the human body can reach more than 10 years. During the incubation period of HIV, patients can live and work for many years without any symptoms. Due to the extremely rapid mutation of HIV, it is difficult to produce a specific vaccine, and there is no effective treatment method so far. AIDS has become a public health problem that seriously threatens the health of people in the world.
Current Status of HIV
Since the beginning of the AIDS epidemic, 79.3 million people have been infected with HIV and 36.3 million people have died from AIDS-related diseases. According to statistics, in 2020, there will be 37.7 million people living with HIV globally, including 36 million adults and 1.7 million children aged 0-14. In 2020, there will be 1.5 million new HIV infections globally, and about 680,000 people will die from AIDS-related diseases. In 2020, some 6.1 million people still do not know they have HIV.
Transmission of HIV
There are three main routes of HIV transmission: sexual contact, blood transmission, and mother-to-child transmission. Ordinary contact does not transmit AIDS.
Clinical Manifestations of HIV
There is a complete natural process from HIV infection to onset. Clinically, it can be divided into four periods. Not every infected person will have a full four-stage performance. The different manifestations of the four periods are a gradual and coherent course of development.
- Acute infection phase: The first stage of HIV infection. After 2 to 4 weeks of HIV infection, infected people will experience cold-like symptoms, such as fever, swollen lymph nodes, pharyngitis, rash, diarrhea, vomiting, and fatigue. Serum HIV antibodies were positive 2-6 weeks after infection.
- Incubation period: This stage is generally 8 to 10 years. Infected people generally do not have obvious symptoms. A small number of infected people develop swollen lymph nodes.
- Pre-AIDS: During this stage, the infected person has persistent or intermittent systemic symptoms and mild opportunistic infections. Systemic symptoms include persistent generalized lymphadenopathy, fatigue, anorexia, fever, weight loss, and thrombocytopenia. Minor infections are mostly manifested in infections of the oral cavity, skin and mucous membranes, including oral candidiasis, gingivitis, skin fungal infections, herpes zoster, folliculitis, and pruritic dermatitis.
- AIDS stage: The immune function is completely collapsed, and the patient will develop pneumonia, esophagitis, lymphoma, pulmonary or extrapulmonary tuberculosis, and HIV-related wasting syndrome, etc., until death.
Treatment of HIV
HIV treatment is expensive. According to the US Centers for Disease Control and Prevention, the lifetime medical costs of a person living with HIV are approximately $485,500. HIV remains one of the world's greatest public health challenges to date.
In terms of AIDS prevention and treatment, patients can currently use high-efficiency antiretroviral therapy for drug control, but it is extremely difficult to cure. At the end of 2020, 27.5 million people worldwide were receiving antiretroviral therapy. At present, there are five main classes of antiretroviral drugs for AIDS: nucleoside reverse transcriptase inhibitors, non-nucleoside reverse transcriptase inhibitors, protease inhibitors, integrase inhibitors, entry inhibitors.
- HIV Reverse Transcriptase Inhibitors
HIV reverse transcriptase is an enzyme necessary for HIV replication. HIV reverse transcriptase reverse-transcribes viral RNA into DNA, which is further reintegrated into the genome of normal cells. HIV reverse transcriptase inhibitors prevent the virus's reverse transcriptase from accurately replicating its RNA into DNA. Without DNA, HIV cannot replicate itself.
Nucleoside reverse transcriptase inhibitors are typically nucleoside/nucleotide analogs of cytidine, guanosine, thymidine, and adenosine. Such drugs can inhibit viral replication by competitively binding to the binding site of reverse transcriptase with the substrate.
Non-nucleoside reverse transcriptase inhibitors inhibit reverse transcriptase by binding to non-substrate-binding allosteric regions. These drugs have low cytotoxicity and fewer adverse reactions.
HIV protease inhibitors can block the necessary protein synthesis in the process of HIV replication and maturation, thereby inhibiting HIV replication and making HIV progeny non-infectious. At present, HIV protease inhibitors have achieved certain clinical effects.
HIV Entry Inhibitor is a new experimental antiretroviral drug. These drugs act on the process of viral adhesion, co-receptor binding and membrane fusion, and can effectively block HIV from invading cells and inhibit viral infection. The use of HIV entry inhibitors alone or in combination with reverse transcriptase inhibitors and protease inhibitors can help improve drug efficacy, reduce toxic side effects, and is expected to save the lives of AIDS patients who are resistant to existing anti-HIV drugs. There are three main classes of HIV entry inhibitors: adsorption inhibitors, coreceptor inhibitors and fusion inhibitors.
HIV integrase inhibitors can prevent the integration of HIV viral DNA with host cell DNA, which is a key step in inhibiting HIV infection and replication in other cells. HIV integrase inhibitors do not harm normal cells and therefore have high selectivity and low toxicity.
- HIV Gag Protein Fragments
The role of Gag molecules provides a new idea for the study of targeting HIV. The Gag protein is one of three gene products encoded by retroviruses. Assembly of HIV is primarily controlled by Gag proteins. Gag proteins recruit viral genomic RNA to virions during viral assembly. Gag protein has self-assembly function and can stimulate humoral and cellular immunity.
- HIV Rev and TAT Fragments
Both TAT and REV are essential viral regulatory proteins for HIV replication. Together, they act as regulators of HIV and play a pivotal role in HIV gene expression. The TAT protein increases the expression of all HIV genes. The REV protein selectively promotes the expression of genes encoding viral structural proteins, promotes the virus from the early stage of infection to the late stage, and acts as a switch to control viral gene expression.
- Cycloviolin Related Peptides
Experiments have shown that cycloviolins are a class of macrocyclic peptides with significant anti-HIV activity.