Anti-Hiv

Background


Immunodeficiency is a state in which an immune system's capability of protecting oneself from infectious diseases is weakened or absent. HIV is short for Human immunodeficiency virus, which is a member of the genus lentivirus, part of the family retroviridae. Two type of HIV have been characterized: HIV-1 and HIV-2. HIV-1 (Human immunodeficiency virus type 1) is a retrovirus that may produce an acute, usually self-limited mononucleosis-like syndrome but more inevitably causes a broad array of progressive clinical manifestations, widely known as the acquired immunodeficiency syndrome (AIDS). HIV-2 (Human immunodeficiency virus type 2) causes a similar but far less widespread infection and a generally more indolent chronic disease. The four major routes of transmission are unprotected sexual intercourse, contaminated needles, vertical transmission or mother-to-child through breast milk. Additionally, viral infection may occur through the transfer of blood, semen, vaginal fluid or pre-ejaculate.

HIV life cycle and targets of therapeutic

HIV-1 is a spherical, enveloped virus approximately 120 nm in diameter. The virus is comprised of two copies of its single-stranded RNA genome that encodes the virus' nine genes. Of these nine genes, the gag, pol and env genes are essential in viral infection and replication as they contain the information needed to make the structural proteins required for new virus particles production. Upon entry into the target cell, the viral RNA genome is transcribed to a doublestranded DNA intermediate by the virally encoded reverse transcriptase and then integrated into the host cell genome by the HIV-1 encoded integrase. Once inside the cell, two pathways are possible: the infection may become a. latent; or b. productive, where a large number of virus particles are synthesized and viral infection spreads

HIV-1 is also well known for its genetic diversity. Phylogenetic analysis of env gene sequences (either whole gene or partial) of HIV-1 isolated obtained from various countries has lad to the classification of HIV-1 into two groups of viruses: M (main) and O (outlier). Within group M, at laest 10 HIV-1 subtypes (A-I) have been identified that are equidistant genetically, forming a starlike phylogeny. Different subtypes of HIV-1 are prevalent in various geographical regions. Subtype B is predomainant in Europe and America, subtype A, C, and D in Africa, and subtype E is encountered mainly in Asia. Knowledge of HIV-1 subtype distribution in a particular country is of importance with respect to possible differences in biological properties as well as to diagnostic problems that may arise when specific subtypes are not recognized by standard screening serological assay or molecular assays used for the detection of viral load.

HIV-2 is a spherical enveloped virus with a diameter of approximately 110 nm. The HIV-2 envelope is encoded by the env gene and consists of a lipid bilayer containing a transmembrane glycoprotein of 36 KDa (gp36) which anchors an outer surface glycoprotein with 125 KDa (gp125). In the mature HIV-2 virion, these heterodimers associate as trimers (gp1253/gp363). In the infected cell, HIV-2 envelope glycoproteins are produced as a 97 KDa polyprotein by translation of a single-spliced mRNA in ribosomes bound to the endoplasmic reticulum.

HIV affects a type of lymphocytes (leukocytes), called CD4 cells (T-helper cells or T-cells), directly in blood. CD4 cells play a important role in protecting body from infecting. The CD4 cells send signals to activate body’s immune reponse when they detect viruses or bacteria. So when a person is infected with HIV, the virus begins to attack and destroy the CD4 cells of the person’s immune system. Then the CD4 count is a test that measure the number of CD4 cells in a sample of the blood, which can help the infected person decide when to start antiretroviral therapy (ART). ART involves taking a combination of HIV medicines every day. It prevents HIV from multiplying and destroying CD4 cells. ART can’t cure HIV, but it can reduce the risk of HIV transmission.

The HIV medicines can be classed into six according to how they fight HIV. They are as blow:

1. Non-nucleoside reverse transcriptase inhibitors (NNRTIs) inhibit reverse transcriptase by binding to an allosteric site of the enzyme. Such as rilpivirine, nevirapine, efavirenz, dapivirine, etravirine, delavirdine, lersivirine, etravirine and so on.

2. Nucleoside reverse transcriptase inhibitors (NRTIs) inhibit reverse transcription. For example abacavir, emtricitabine, tenofovir, zidovudine and zalcitabine.

3. Protease inhibitors (PIs) prevent new HIV from becoming a mature virus that can infect other CD4 cells. Including amprenavir, darunavir, fosamprenavir, indinavir and lopinavir.

4. Fusion inhibitors prevents HIV from entering the CD4 cell.

5. Inteqrase stand transfer inhibitors (INSTIs) inhibit the viral enzyme integrase, which insert its viral DNA into the DNA of the host CD4 cell. Such as elvitegravir, cabotegravir, cobicistat, dolutegravir, and so on.

6. CCR5 antagonists block the CCR5 coreceptor on the surface of certain immune cells. cenicriviroc is this kind of medicine.

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