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Human immunodeficiency virus (HIV) damages cells of the immune system in particular CD4 cells or T cells leading to reduced numbers. This, therefore, lowers the ability to fight off infections and diseases. Over time the immune system becomes weaker and weaker until the final stage of HIV is reached, Acquired immune deficiency syndrome (AIDS). The severity of AIDS makes suffers highly susceptible to life-threatening conditions for example cancers. There is currently no cure for HIV and AIDS, however, it can be managed effectively with the right treatment plans. Through time the way we view and treat HIV has drastically changed. This essay will discuss the symptoms and spread the virus as well as how HIV was dealt with and diagnosed in the past and present. It will also cover possible future advances in treatments for the disease.
Causes, Symptoms and Spread of HIV
The HIV virus is round and has a 100nm diameter with a lipid bilayer membrane envelope (Transfus Med Hemother 2016). It is a retrovirus with two forms HIV-1 and HIV-2, HIV-1 has the highest prevalence. The two forms genomes differ by 55% meaning that a test for HIV-1 will not necessarily detect HIV-2 (Aidsmap 2012). The retroviruses produce a number of regulatory proteins. One of these is called Nef, this protein prevents CD4 being displayed on the host cell surface membrane resulting in deficiency causing reduced immune response. Nef increases pathogenicity more in HIV-1 than HIV-2 due to it having a lower amino acid structure in HIV-1 (Transfus Med Hemother 2016). Infection occurs when the virus enters the host cells it can do this by crossing a mucous membrane, entering damaged skin, entering the skin when pierced with a contaminated object and passed from infected mother to her foetus. HIV is spread via sexual intercourse by the viral cell binding to dendritic cells of the immune system and then pass through the lipid bilayer, replicating inside the dendritic cell using the hosts components.
Early symptoms of human immunodeficiency virus occur 2-6 weeks infection from the pathogen, it is normally in the form of a short illness with similarities to the flu. Following this, there may not be any other signs of HIV for a long period of time even though the virus is still continually destroying CD4 cells weakening the immune response. Symptoms are not particularly specific therefore diagnosis is difficult because carriers do not know they have acquired the disease. Risk is highest in; black Africans, homosexual men and individuals who share needles (NHS 2018). It has a higher frequency in homosexual men due to an increased chance of transmission during unprotected anal sex rather than vaginal or oral intercourse. Prevalence of HIV-2 in black Africans is because high percentages of the population carrying the disease with lack of diagnosis, treatment and education, this also leads to large numbers of children being infected from their mothers during pregnancy.
Past spread and treatment of HIV
Between 1981 and 2003 Human immunodeficiency virus infected 60 million people worldwide causing fatality in more than 20 million of these individuals (Nature Medicine 2003). The HIV virus is thought to have first spread to the human population in the 1920s. The disease originated from Simian immunodeficiency virus (SIV) in African Mangabey monkeys, once this virus passed to humans from consuming infected monkey meat, it mutated leading to HIV-2. Evidence of positive responses to HIV antibodies from isolated SIV in chimpanzees suggests HIV-1 diverged from SIV in chimpanzees located in Gabon (Springer 2018). The epidemic came to worldwide attention in the early 1980s, at this time the first cases of AIDS were identified. The disease caused mass panic and false ideas about the spread of the disease due to the lack of research at the time. HIV was largely associated with the gay male population and drug users creating a stigma around the disease.
In 1983 HIV-1 was isolated for the first time in the Institut Pasteur, Paris, France (Nature Microbiology 2013). The pathogen being identified allowed epidemiological tests to be carried out revealing that HIV was the cause of AIDS. The isolation of the HIV-1 virus allowed antibody structure to be analysed so a diagnostic test for their presence on large scale could be used. This meant blood for transfusion could be successfully screened preventing infection. Testing meant doctors could identify sufferers in the early stages of the disease so the progress of the illness could be monitored, meaning symptoms could be established. In 1984 it was discovered that CD4 class of T lymphocytes were the main receptor for HIV (Nature medicine 2003). Further structural analysis distinguished the presence and structure of; 3 structural gene and 6 regulatory genes, together coding for 15 proteins essential for HIV viral replication. Knowing the method of replication process of the virus was key in identifying effective drug targets (Nature Medicine 2003). The research at this time was extremely important for later development of antiretroviral drugs for the treatment of HIV and AIDs that are available at the present, which are capable of greatly extending life expectancy and quality.
Present treatment and prevalence of HIV
In 2017 approximately 1.8 million people were newly infected by the virus and between 31.1-43.9 million were living with HIV (UNAIDS 2018). At the present day, there is still no definite cure for the disease. Despite this, there is high availability of emergency preventative treatments and antiretroviral drugs. These drugs reduce risk and increase the quality of life for people with the danger of contracting the disease or existing sufferers.
Post-exposure prophylaxis (PEP) is an emergency medication for patients who believe they may have come into contact with the virus. After taking PEP when HIV enters the cell activity of reverse transcriptase is reduced meaning it is less likely for the virus to be able to replicate. Replication is decreased because nucleoside reverse transcriptase is inhibited leading to termination of the replicating chains after they have been integrated into viral DNA. Research shows that the medication can reduce chances of contraction by over 80% (Canadas source for HIV and hepatitis c information 2018).
For patients who are already HIV positive, antiretroviral drugs play a key part in treatment. Each particular group of these drugs for HIV carriers have different targets to cause action including; reverse transcriptase inhibitors, viral protease inhibitors, integrase inhibitors, maturation inhibition and viral entry inhibitors. Reverse transcriptase inhibitors can be used in HIV sufferers as well as in emergency medicine and work via the same method as explained in PEP to reduce replication. Protease inhibitors target viral proteases e.g. HIV aspartyl protease, these enzymes cleave new precursor proteins. When the proteases are inhibited viral polyproteins cannot get split into smaller proteins, therefore, do not gain their functional or structural roles. Integrase inhibitors; MK-0518 and GS-9137 being the most common have the ability to prevent the strand transfer reaction. This reduces the stability of the viral genome as well as hindering expression of genes. 3-O-(32, 32-dimethylsuccinyl)-betulinic acid (Bevirimat) can act as a maturation inhibitor. It interferes with the processing of HIV group-specific antigen (gag proteins) which make up 50% of viral particle mass (Trends in MIcrobiology 2013). This interference stops maturation of capsid protein p25 rendering the HIV particle non-infectious. Viral entry inhibitors block non-specific interaction with heparan sulphates on the membrane of CD4 cells preventing HIV from fusing and subsequently entering. The use of medication can be successful in reducing symptoms and occurrence of the disease, however, the prevalence of HIV is still significant at this time.
Future Treatment of HIV
For the first time, there is evidence pointing towards the possibility of cures for HIV. With the development of gene editing and transplanting techniques in recent years, studies are now being done to attempt to utilise them in HIV treatment. In 2007 the first man became HIV free after a bone marrow transplant to treat cancer (New scientist 2019). One other person has been cured of the disease in the same way, with another reported but not confirmed in March 2019. All three of these patients were suffering from leukaemia or Hodgkin’s lymphoma and received a bone marrow transplant. As part of the method of the transplants, large quantities of their immune cells were destroyed via radiotherapy or medications and have to be replaced with donor cells. In these cases, the cells of donor bone marrow have a mutation in the CCR5 gene (New scientist 2019). The mutation is a 32 nucleotide deletion in a gene coding for beta chemokine receptor. The deletion provides resistance To HIV-1, however, is rare with 0.0808 frequency in Caucasians (Nature medicine 1996). Although this has the possibility of being a cure, the risks associated are extremely high and therefore should only be used as a last resort. However, the discovery of this has shown the potential of using genetic engineering to treat HIV/AIDs.
CRISPR/CAS9 is a part of DNA which contains short tandem base repeats. It can be used as a genetic engineering tool that uses the CRISPR sequence and its associated proteins to edit DNA. CRISPR sequences can be modified allowing it to recognise sections of bases in HIV-1 promoters. This means that the promoter sequence can be excised from host DNA. Modified CRISPR has been used in the lab on T-lymphocyte cell lines containing integrated HIV-1 and green fluorescent marker proteins. HIV-1 gene expression was inhibited in these cells (Nature 2016). Gene editing also could have the ability to give immunity to HIV. This could be done by using CRISPR/CAS9 to edit B-cells. Edited B-cell could produce improved versions of antibodies in vitro, these antibodies potentially would be given to people with a high risk of contracting the virus in the form of injection (New Scientist 2019). After the occurrence of HIV being cured, action has been taken to find less harmful techniques for use on the general population.
In conclusion, the way we treat and view HIV/AIDS has changed. When first cases appeared little was known and there was fear around the virus due to the high chance of fatality. The disease is no longer the life sentence it once was. Biomedical research has played a key part in saving millions of lives. New treatments allow people who have contracted the disease to live longer and people at risk of the disease to live with less danger. Discoveries from the past of the action and targets of virus have been built on giving the medications we have today. With greater technology, research to develop a cure can occur. This differs from the present where we can only prevent transmission and reduce symptoms once infected. The future for people suffering from HIV/AIDS looks promising, however, it may be some time before a worldwide cure can be established.
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