Overview of Anti-HIV Drugs

AIDS, Acquired Immune Deficiency Syndrome, is a malignant infectious disease with a very high fatality rate caused by HIV (human immunodeficiency virus). HIV invades the human body and can destroy the human immune system, causing the infected person to gradually lose the ability to resist various diseases, and eventually die. There is neither vaccine for prevention, nor any effective medicine to cure this disease. AIDS was named in 1982, of which the pathogen was discovered in 1983. It is one of the most tricky medical problems. HIV belongs to the primate immunodeficiency virus subgenus in the Lentivirus genus of the Retroviridae family. There are two kinds of HIV discovered. HIV-1 (https://www.creativebiolabs.net/symbolsearch_HIV-1.htm) is a virus strain isolated from Europe and America, which has only about 45% similarity with monkey HIV. It is very pathogenic and is the main pathogen causing the global AIDS epidemic. The similarity between HIV-2 and monkey HIV is as much as 75%. The virulence of HIV-2 is weak, causing longer course of AIDS and the symptoms are mild. HIV-2 mainly occurs in West Africa. Therefore, the research mainly focuses on HIV-1. HIV is a globular virus with a diameter of about 100 nm, which is surrounded by a lipid membrane composed of two layers of lipid that is derived from the outer membrane of host cell with many glycoprotein molecules (mainly gp41 and gp120). The proteins p24 and p18 form the core, which contains a genomic RNA chain, attached by a reverse transcriptase that catalyzes the reverse transcription of viral RNA. According to data released by the CDC, there are currently about 1.1 million people living with HIV in the United States, and about 15% of them do not know they have been infected. In 2016, about 38,700 Americans were newly infected with HIV, among which, homosexuals, bisexuals, and others who have sex with men are at the highest risk of infection, with an estimated 2,600 new infections annually. In 2017, 38,739 people in the United States were diagnosed with HIV infection. Since 2013, the number of new cases in the United States remained stable. In addition, there are regional differences in HIV infection that in 2017, 19,968 (52%) located in the southern United States. The goals of current anti-HIV drugs are: * Reduce the plasma HIV RNA to undetectable levels. * The number of CD4 cells returned to normal levels (immune restoration or reconstitution). The most commonly used treatment is highly active antiretroviral therapy (HAART). There are currently more than 30 related drugs (including compound preparations) in the world, including nucleoside reverse transcriptase inhibitors (NRTIs), non-nucleoside reverse transcriptase inhibitors (NNRTIs), and protease inhibitors (PIs), integrase inhibitors (INSTIs), membrane fusion inhibitors (FIs), and CCR5 inhibitors. According to The Physical Activity Guidelines for Americans issued by the U.S. Department of Health and Human Services (HHS), the choice of treatment should be based on virological efficacy, potential adverse reactions, fertility potential and the use of effective contraceptive measures, drug burden, dosing frequency, drug-drug interaction potential, comorbid conditions, cost, accessibility, and drug resistance test results. For newly treated patients, the combined use of 1 INSTI and 2 NRTIs is recommended. Since 1995, there are 60 anti-HIV drugs on the global market, of which 49 were launched by the United States. Those are mainly chemical drugs. Currently, apart from chemical drugs, only one biological drug and one botanical drug are on the market. The Biopharmaceutical drug is the CD4 monoclonal antibody—Ibalizumab developed by Biogen, which was approved by the FDA in 2018 and approved by the European Union in 2019. The botanical drug is Hiviral from Nerium Biotechnology Inc, a plant extract that was launched in South America in 2007. In 2018, the annual sales of anti-HIV drugs were 31.6 billion USD. North America is the largest market, with a share of 71.7% in 2018. Among anti-HIV drugs, HAART accounted for more than 50% of the market share, followed by nucleoside reverse transcriptase inhibitors. Membrane fusion inhibitors have a market share of less than 1%.