| Wednesday, April 16, 2008 |
| HIV - Aids |
HIV stands for Human Immunodeficiency Virus and leads to the development of Acquired Immune Deficiency Syndrome or AIDS. AIDS is not a disease itself but a failure of the immune system which leads to a collection of rare, life-threatening opportunistic infection.
Since AIDS was first recognised on 1st December 1981 it is estimated to have killed 25million people. HIV/AIDS is now pandemic which means it has spread across whole continents and in this case the world. It is thought that at the moment there are 40million people worldwide, living with HIV, 70% of them living in sub-Saharan Africa. Although HIV and AIDS are a major problem in developing countries and a leading cause of death it still has a massive impact here in the UK: about 63,500 people are now living with HIV.
HIV is a pathogen which is an organism that causes infectious disease; more specifically it is a retrovirus which means it breaks down DNA in cells and reassembles it in order to make copies of itself. HIV is such a problem for a number of reasons: firstly it can mutate easily so it is difficult for the body to recognise and it is difficult to develop a vaccine, secondly it attacks T-helper lymphocyte cells which are a vital part of the body's immune system.
HIV is transferred through the direct exchange of:
* Blood
* Semen
* Vaginal fluid
* Pre-ejaculate
* Breast milk
It can be transmitted by:
* Unprotected sexual intercourse
* Contaminated needles
* Breast milk
* Vertical transmission (from the mother to the baby at birth)
* Blood transfusions or blood products
HIV can't survive outside the body or be carried in a vector so it is only transferred through direct contact. However, it is present in bodily fluids as both a free virus and within infected immune cells. Saliva, sweat and urine do contain HIV if the person is infected but not in a high enough quantity to transfer the infection.
Symptoms of HIV:
* Fever
* Swollen glands
* Sore throat
* Rash
* Painful muscles and joints
* Headache
* Nausea and vomiting
* Ulcers
* Flu-like symptoms.
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There are 4 stages in HIV infection, these are:
1. The Incubation Phase:
This stage is often asymptomatic and normally lasts 2-4 weeks.
2. Acute HIV Infection:
In this stage you develop an influenza-like illness with symptoms such as fever, weight loss, thrush and neurological symptoms. These symptoms are very non-specific so it is often not recognised as an HIV infection and can be diagnosed incorrectly as a more common infection with similar symptoms. The virus replicates rapidly and there is a marked drop in the number of T-helper lymphocytes. This stage lasts for at least a week and more normally a month.
3. Latency Stage:
The body's natural, strong immune defence reduces the number of viral particles in the blood and the infection seems to clear. This stage can last any time between 2 weeks and 20 years.
4. AIDS:
The T-helper lymphocytes decline in number so cell-mediated immunity is lost. This allows opportunistic infections to occur such as tumours, tuberculosis and pneumonia and it is these infections that actually kill the person.
Replication Cycle of HIV:
HIV has surface receptors called glycoprotein 120 and glycoprotein 41. Glycoprotein 120 attaches to the CD4 antigen receptors on the host cell. The virus releases an enzyme called lysozyme which digests part of the membrane, the viral envelope and the host's cell membrane fuse together. The virus' genetic material, RNA, is injected into the host cell along with the enzymes reverse transcriptase, protease, integrase and ribonuclease. In the cytoplasm reverse transcriptase makes a complimentary strand of DNA from the virus' RNA genome; it then makes a second complementary strand of DNA to form a double strand of DNA. Mutations often occur during transcription. The new DNA is transported to the cell nucleus and integrated into the host's DNA. When the cell replicates it also replicates the viral DNA which codes for the production of proteins to make new viruses. IT can lie dormant in the host's cell DNA or it can be activated by the host. When it is activated RNA is made from DNA to make the viral RNA genome. The RNA is translated to make viral enzymes and proteins, some functional proteins are formed by using the enzyme protease to cleave or cut a long polypeptide chain. Newly formed glycoproteins 120 and 41 are inserted into the host's cell membrane, the structural proteins surround the viral RNA forming a core and the virus is released from the cell by budding off. The rate of replication is fast, and therefore so is the rate of mutation. This means that there are many different strands of HIV making it difficult for the body to recognise and fight them and it is also difficult to develop an effective vaccine.
The Immune Response and T-helper Lymphocytes:
T lymphocytes are a specific type of white blood cell which are produced in the bone marrow and mature in the thymus. Mature lymphocytes circulate in the blood. T cells have specific surface receptors, similar to antibodies, which are specific to one antigen (a substance that is foreign to the body). This means that they are able to recognise a particular virus or bacterium etc. There are many T cells and different ones will have different receptors that recognise a different antigen. When the cells encounter an antigen in contact with a host cell they become activated. Activated T-helper cells release cytokines, (these are similar to hormones and are involved in cellular communication,) which stimulate another type of lymphocyte called B lymphocytes. These cells produce specific antibodies for the antigen, which either attract other immune cells to the site so that they can kill them or they help break up the antigen themselves. Cytokines can also stimulate a third type of immune cell, called macrophages, to kill the foreign particles. As well as secreting cytokines T-helper cells also divide to form memory cells so that if the person is infected by the same antigen the immune response will be quicker and more effective. . So although T-helper cells don't fight the antigens themselves they play a key role in recognition and stimulating attacks and when their numbers are low the body is unable to defend itself properly.
HIV infects and destroys cells which express a surface protein known as CD4. This includes primarily T-helper cells, but also macrophages and dendritic cells (other immune cells). The number of CD4+ T-helper cells drops meaning that the full range of antigens that could be detected aren't recognised. This is the core symptom of AIDS: pathogens that would normally be detected by T cells escape recognition allowing opportunistic infections to attack.
Prevention and Treatment:
At the moment there isn't a cure or a vaccine for either HIV or AIDS. This is mainly because the virus readily mutates so there are many different strands and although there might be a vaccine for one strand there will be other strands that are resistant and can continue to replicate and infect people. Therefore the best defense against HIV is prevention and avoiding exposure to the virus.
This can be done in a number of ways:
* Using condoms and not having unprotected sexual intercourse.
* Not breast-feeding your children if you are HIV+.
* Not sharing needles or other drug paraphernalia.
* Using sterile equipment, for example those used in surgery, tattooing and body piercing.
People at high risk are:
* Male homosexuals
* Prostitutes
* Injecting drug users
* Sexual partners of infected people.
In developed countries blood and blood products, such as organs, from donors are screened for HIV and heat-treated to kill any infections before they are used. However, this is not widely practised in the developing world and anybody undergoing an operation or blood transfusion in these countries is often asked to use their own blood for the operation.
Blood tests can be used to detect antibodies for HIV to identify infected people and to determine whether someone is HIV+ (infected). However antibodies to HIV can take up to three months to appear in the blood after infection, so you may test as negative but still be infected with HIV, also testing negative doesn't mean that you can't be infected by HIV.
It is difficult to control the spread of the HIV infection because it has a long latent stage between being infected and developing AIDS, also HIV can be asymptomatic so people may be unaware that they are infected. In the UK contact tracing is used where people diagnosed with HIV, if they want to or are able to, identify people they may have put at risk or may have infected them so that those people can be offered HIV tests.
Drug therapy has also been developed to slow the onset of AIDS, but it doesn't cure you or stop you from infecting other people. The drugs are expensive and have side effects such as: rashes, headaches and diarrhoea which are mild and temporary as well as nerve damage and abnormal fat distribution which are severe and permanent. Other side effects include insulin resistance, increase in the risk of cardiovascular disease and birth defects. Since they are expensive many infected people especially those in developing countries, do not have access to them. At the moment antiretroviral treatments are used and should be given as soon as possible after exposure to reduce the risk of infection.
The main treatment is Highly Active Antiretroviral Therapy or HAART which is a combination of at least three drugs. If used correctly and started at the right time it may increase the life expectancy by an average of 32 years from the time of infection. Without HAART the progression of HIV to AIDS is about 9-10 years, and the survival expectancy after developing AIDS is about 9.2months. However, in some circumstances HAART is effective in less then 50% of patients. This is mainly due to non-adherence and non-persistence; HAART involves a complex, strict regime with a number of drugs such as how many pills to take and when. It may also be due to medication intolerance, side effects or infection by drug resistant strains.
HAART prevents the virus from replicating and allows the immune system to recover so the number of viral particles in the blood is reduced. The drugs used are similar to DNA nucleotides, which are the bases that make up the sequence of the genetic code. The drugs bind to the viral enzyme reverse transcriptase and block its action so that the viral genetic material can't replicate and the number of lymphocytes increases.
The drugs that are used for HAART are from several different classes. They include:
1. Nucleoside Reverse Transcriptase Inhibitors (NRTI): These prevent HIV from copying its' genetic material and therefore stops it multiplying.
2. Protease Inhibitors: These prevent the virus from assembling its' protective protein coat as it stops protease from cleaving the long polypeptide chain into functional proteins so it isn't fully formed and can't operate.
3. Non-Nucleoside Reverse Transcriptase Inhibitors (NNRTI): These are similar to NRTIs.
4. HIV-fusion inhibitors: these stop HIV from fusing to the host's cells so it can't enter and change the genetic material. |
| posted by Healthy Life @ 9:36 AM |
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