HIV Antiretroviral Drugs

Hiv stands for Human Immunodeficiency Virus and leads to the improvement of Acquired Immune scantness Syndrome or Aids. Aids is not a disease itself but a failure of the immune law which leads to a range 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 over whole continents and in this case the world. It is concept that at the occasion there are 40million citizen worldwide, living with Hiv, 70% of them living in sub-Saharan Africa. Although Hiv and Aids are a major question in developing countries and a prominent cause of death it still has a heavy impact here in the Uk: about 63,500 citizen are now living with Hiv.

Drugs For 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 question for a amount of reasons: firstly it can mutate unmistakably so it is difficult for the body to recognise and it is difficult to fabricate a vaccine, secondly it attacks T-helper lymphocyte cells which are a vital part of the body's immune system.

Hiv is transferred straight through the direct transfer 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 surface the body or be carried in a vector so it is only transferred straight through direct contact. However, it is present in corporeal fluids as both a free virus and within infected immune cells. Saliva, sweat and urine do contain Hiv if the man 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.
*

There are 4 stages in Hiv infection, these are:

1. The Incubation Phase:

This stage is often asymptomatic and usually lasts 2-4 weeks.

2. Acute Hiv Infection:

In this stage you fabricate 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 tasteless infection with similar symptoms. The virus replicates rapidly and there is a marked drop in the amount of T-helper lymphocytes. This stage lasts for at least a week and more usually a month.

3. Latency Stage:

The body's natural, strong immune defence reduces the amount 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 amount so cell-mediated immunity is lost. This allows opportunistic infections to occur such as tumours, tuberculosis and pneumonia and it is these infections that unmistakably 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 duplicate strand of Dna. Mutations often occur during transcription. The new Dna is conveyable 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 yield 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 bind 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 separate strands of Hiv manufacture it difficult for the body to recognise and fight them and it is also difficult to fabricate an effective vaccine.

The Immune Response and T-helper Lymphocytes:

T lymphocytes are a definite 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 definite surface receptors, similar to antibodies, which are definite to one antigen (a substance that is foreign to the body). This means that they are able to recognise a single virus or bacterium etc. There are many T cells and separate ones will have separate receptors that recognise a separate antigen. When the cells encounter an antigen in contact with a host cell they come to be activated. Activated T-helper cells issue cytokines, (these are similar to hormones and are complicated in cellular communication,) which stimulate other type of lymphocyte called B lymphocytes. These cells produce definite antibodies for the antigen, which whether 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 man 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 amount 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 usually be detected by T cells flee recognition allowing opportunistic infections to attack.

Prevention and Treatment:

At the occasion there isn't a cure or a vaccine for whether Hiv or Aids. This is in general because the virus effortlessly mutates so there are many separate 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 amount 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 performance 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 citizen and to resolve whether man 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 operate 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 citizen may be unaware that they are infected. In the Uk contact tracing is used where citizen diagnosed with Hiv, if they want to or are able to, identify citizen they may have put at risk or may have infected them so that those citizen 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 costly 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 contain insulin resistance, growth in the risk of cardiovascular disease and birth defects. Since they are costly many infected citizen especially those in developing countries, do not have way to them. At the occasion antiretroviral treatments are used and should be given as soon as possible after exposure to cut the risk of infection.

The main medicine is extremely Active Antiretroviral Therapy or Haart which is a composition of at least three drugs. If used correctly and started at the right time it may growth 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 in general due to non-adherence and non-persistence; Haart involves a complex, definite regime with a amount 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 law to recover so the amount 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 operation so that the viral genetic material can't replicate and the amount of lymphocytes increases.

The drugs that are used for Haart are from some separate classes. They include:

1. Nucleoside Reverse Transcriptase Inhibitors (Nrti): These forestall Hiv from copying its' genetic material and therefore stops it multiplying.

2. Protease Inhibitors: These forestall 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 convert the genetic material.

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