The Biology of AIDS

HIV is the virus which causes the fatal disease of the immune system, Aids.
At least 28 million people worldwide have died from Aids – their bodies' defence systems ravaged by the HIV virus to the point where everyday infections become life-threatening.
More than 20 years since HIV was first recognised, there remains no vaccine against HIV and no cure for Aids, although a new generation of drugs has dramatically extended the life expectancy of those who contract HIV.



The HIV virus attacking an immune cell

THE HIV VIRUS
HIV - the Human Immunodeficiency Virus - targets the immune system, the very system which would normally defend the body against infections.
The virus attacks a particular type of white blood cells called CD4+ cells. It hijacks the cell, inserts its own genes into the cell's DNA and uses it to manufacture more virus particles. These go on to infect other cells.
The CD4+ host cells eventually die, although scientists do not know exactly how.
The body's ability to fight diseases decreases as the number of CD4+ cells drops, until it reaches a critical point at which the patient is said to have Aids - Acquired Immune Deficiency Syndrome.
HIV is a particular kind of virus – a retrovirus. While simpler than ordinary viruses, retroviruses tend to be harder to defeat.
They embed their genes into the DNA of the cells they target, so that any new cells that the host cell produces also contain the virus genes.
Retroviruses also copy their genes into the target cell with a high level of error. In combination with HIV's high replication rate, this means the virus mutates at speed as it spreads.
Furthermore, the "envelope" the HIV virus particle is contained inside is made of the same material as some human cells, making it difficult for the immune system to distinguish between virus particles and healthy cells.
HOW HIV REPLICATE:

Virus attaches: Proteins on the HIV virus "dock" with CD4 receptors on the target cell.
Genes copied: The HIV virus makes a copy of its own genetic material.
Replication: The virus inserts this copy into the host cell’s DNA. When the cell reproduces, it manufactures the parts of the HIV virus.
Release: The parts are assembled and form a "bud", which breaks off to become a new HIV virus.

CD4+ cell
An immune system cell which plays a key role in orchestrating the way the immune system attacks foreign invaders. HIV infection leads to the destruction of these cells, leaving the immune system less able to fight infection. A normal CD4+ count in a healthy, HIV negative adult is usually between 600 and 1200 per cubic millimetre of blood. In an Aids patient it is usually below 200.

THE INFECTION
HIV is present in the blood, sexual fluids and breast milk of people who are infected with the virus.
It is passed on when these infected fluids get into another person's system.
You can contract HIV by:
· Having unprotected sexual intercourse with someone who is infected
· Sharing needles or body piercing equipment with someone who is infected
· Being given a transfusion of infected blood
· Allowing infected fluids to get into a cut or sore anywhere on your body
· Babies born to HIV positive women can be infected during pregnancy and birth, or through breast feeding
HIV is present in the saliva of an infected person, but not in quantities sufficient to transmit infection. Once infected fluids have dried, the risk of them transmitting the virus is considered to be close to zero.
The key methods of preventing the transmission of HIV are by not having sex with anyone who is, or may be, HIV positive, or by using latex condoms.
Latex condoms are essentially impermeable to HIV-sized particles. If used properly and consistently, they are considered highly effective in reducing the risk of transmission – although no protective method other than abstinence is 100% safe.
Injecting drug users can reduce the risk of contracting HIV by not sharing needles

The HIV virus - present in blood and sexual fluids

HIV myths
HIV cannot be caught:
· through the air, or by coughing and sneezing
· by kissing, touching or shaking hands
· by sharing crockery or cutlery
· through contact with toilet seats
· through insect or animal bites
· through swimming pools
· by eating food prepared by someone with HIV

EARLY STAGES
About half of people who contract HIV suffer flu-like symptoms within the first two to four weeks of infection.
These include fevers, fatigue and rashes, sore joints, headaches and swollen lymph nodes.
The graph on the right shows the course of a typical HIV infection over time. The CD4+ cell count is the number of CD4+ cells per cubic millimetre of blood, and decreases as the virus progresses.
A healthy immune system has 600 – 1200 cells per cubic millimetre of blood. If this drops as low as 200, the patient is considered to have Aids.
The "viral load" is the number of virus particles per millilitre of blood. Initially, this peaks as the virus replicates rapidly in the bloodstream.
Within six to twelve weeks of infection, the body starts producing a specific type of antibody, or disease-fighting protein.
While not very effective in fighting the virus, the antibody is a reliable indicator of whether someone is infected.
The most common HIV test detects the antibodies. This means that a person may infect others as soon as he or she becomes infected, but will not test positive for several weeks.
Some people with HIV may live for several years before developing Aids, feeling healthy and with no outward signs of the virus.
Others may suffer symptoms such as weight loss, fevers and sweats, frequent yeast infections, rashes and short-term memory loss while living with HIV
THE PROGRESSION OF HIV


AIDS DEVELOP
As the immune system becomes damaged, it loses its capacity to fight disease and infections can become life-threatening.
People who are HIV positive are more susceptible to widespread diseases such as tuberculosis, malaria, pneumonia and shingles. Their vulnerability increases as their CD4+ cell count drops.
HIV patients also become vulnerable to a host of "opportunistic infections". These are infections caused by common bacteria, funguses and parasites which healthy bodies can fight, but which can cause illness and in some cases death in people with damaged immune systems.
Some of these are likely to occur at higher CD4+ counts than others. Most become active below CD4+ counts of 200, the point where Aids develops.
If full medical care is available, patients can be given drugs which treat and guard against some of these infections, although these are sometimes expensive and can cause side effects.











Anti-HIV Drugs
Since the start of the HIV epidemic, a series of drugs have been developed which significantly prolong the lives of people who are HIV positive
Called "antiretroviral drugs", they block the virus's ability to replicate.
They can delay the onset of Aids by slowing the loss of patients' CD4+ cells, but they are not a cure.
There are four main classes of drugs, operating at different points in the HIV cycle, as shown on the diagram on the right.
A wide range of side effects are associated with antiretroviral therapy.
Many patients experience nausea, vomiting, headaches, fatigue, rashes, diarrhoea, insomnia, stomach pain and numbness around the mouth.
Inflammation of the pancreas, damage to the liver and nerves, changes in body shape, anaemia and muscle pain can also result from some of the drugs.
Antiretroviral drugs should be taken in combination. Usually three different drugs, from at least two different classes, are used at once.
As HIV mutates, some versions of the virus become resistant to drugs. The chances of keeping it in check are therefore much higher if several drugs are used.
Pill-taking regimes can be complicated and involve taking tablets at very specific times during the day.
If such programmes are not followed properly, the likelihood of the virus growing resistant to the drugs increases.
Some people are now becoming infected with strains of the virus which are already resistant to particular drugs.

Entry inhibitors bind to the proteins on the outside of the HIV virus and stop it from entering the target cell (Fuzeon only).
Nucleoside reverse transcriptase inhibitors stop HIV copying its genes into the cell. Nucleosides are the building block for genes. The drugs supply faulty versions of these building blocks (drugs include abacavir, AZT, ddI, 3TC).
Non-nucleoside reverse transcriptase inhibitors also block the gene-copying process. They disable the enzyme that controls it (drugs include nevirapine and efavirenz).
Protease inhibitors disable protease, an enzyme which plays a key role in the formation of the new virus (drugs include amprenavir, lopinavir, ritonavir, nelfinavir).


HIV GLOSSARY
Acquired Immunodeficiency Syndrome (Aids)
The most severe result of HIV infection, occurring when the immune system is effectively disabled.
People with Aids often have infections of the lungs, brain, eyes and other organs. They may often also experience severe weight loss, diarrhea and certain types of cancer.

Antibodies
Proteins produced by the immune system to neutralise infections or malignant cells.

Antigen
Any foreign substance, such as a virus, bacterium or protein, that triggers an immune response by stimulating the production of antibodies.

Antiretroviral drugs
Substances used to kill or inhibit the multiplication of retroviruses such as HIV.

CD4+ cell
An immune system cell which plays a key role in orchestrating the way the immune system attacks foreign invaders. HIV infection leads to the destruction of these cells, leaving the immune system less able to fight infection. A normal CD4+ count in a healthy, HIV negative adult is usually between 600 and 1200 per cubic millimetre of blood. In an Aids patient it is usually below 200.

Combination therapy
Two or more antiretroviral drugs or treatments used together to achieve optimum results against HIV infection and/or Aids. Combining drugs has proved to be more effective at reducing the amount of the HIV in the body than the use of single drugs by themselves. An example of combination therapy would be the use of two nucleoside analogue drugs plus either a protease inhibitor or a non-nucleoside reverse transcription inhibitor.

Fusion inhibitors
A class of drugs which prevent HIV from penetrating the host cell. There is currently just one fusion inhibitor available, Fuzeon.

DNA
Deoxyribonucleic acid (DNA) molecules are known as the building blocks of life. They carry the genetic information necessary to create cells and to ensure that they function in the right way.

Enzymes
Proteins that stimulate particular chemical reactions.

Highly active antiretroviral therapy (HAART)
A combination of three or four different drug treatments which has been found to be an effective way to block the progress of HIV, and to reduce the amount of virus to the level where it becomes undetectable in a patient's blood.

Human immunodeficiency virus type 1 (HIV-1)
The virus which is thought to cause most cases of Aids. Infection occurs when the virus inserts its own genetic material into a host cell, preventing it from carrying out its natural functions and turning it into an HIV factory.

Human immunodeficiency virus type 2 (HIV-2)
A virus closely related to HIV-1 that has also been found to cause Aids. It was first isolated in West Africa.

Immune system
The body's defence mechanism, which seeks out and destroys foreign invaders.

Integrase inhibitors
Drugs currently under development which interfere with HIV's integrase enzyme. Integrase plays a key role in the process where the HIV virus inserts its own genetic material into the host cell in order to use the cell to make new virus particles.

Kaposi's sarcoma
A type of cancer closely associated with Aids. It usually appears as pink or purple painless spots on the skin or inside the mouth. It can also attack the eyes and occur internally.

Long-term non-progressor
An individual who has been living with HIV for at least 7 to 12 years and has a stable CD4+ cell count despite not having had antiretroviral therapy.

Macrophage
A large immune cell that devours infectious material and other foreign invaders, as well as stimulating other immune cells. Macrophages can harbour large quantities of HIV without being killed, acting as reservoirs of the virus.

Opportunistic infection
An infection which occurs in people with defective immune systems and is caused by an organism that does not usually cause illness in people with healthy immune systems.

Protein
A large molecule composed of one or more chains of smaller molecules called amino acids. Proteins are required for the structure, function and regulation of the body's cells, tissues and organs. Examples are hormones, enzymes, and antibodies.

Protease inhibitors
A class of antiretroviral drugs, designed to interfere with the action of HIV's protease enzyme. Protease works as "chemical scissors" to cut up newly created chains of protein into smaller pieces. These pieces are then used to build new HIV virus particles.

Resistance
Experts are concerned that HIV is becoming immune to previously effective drugs. This is because the virus has the ability to mutate rapidly.

Retrovirus
A rudimentary form of virus which carries its genetic information in the form of RNA. This means that it can easily be copied into the DNA of the host cell's chromosomes. HIV is a retrovirus - some other members of the retrovirus family cause cancers.

Reverse transcriptase inhibitors
Drugs which interfere with an enzyme called reverse transcriptase, which HIV needs in order to copy its genes into the host cell and reproduce itself. These are the oldest class of antiretroviral drugs, and come in three different forms, each of which has a slightly different mode of action. The three types are: nucleoside reverse transcriptase inhibitors, nucleotide reverse transcriptase inhibitors and non-nucleoside reverse transcriptase inhibitors.

RNA
A molecule similar in structure to DNA which transmits genetic information from DNA to other parts of the cell, and controls certain chemical processes within the cell.

T cell
A white blood cell which orchestrates the immune system's response to infected or malignant cells. CD4+ cells, which HIV targets, are a particular type of T cell.

Transmission
The process by which the virus is passed from one individual to another. HIV is transmitted through body fluids, particularly blood, semen, vaginal secretions and breast milk. The most common forms of transmission are through unprotected sexual intercourse, by sharing needles when injecting drugs and from mother to child when breastfeeding.

Viral load
The amount of HIV in the blood, measured in the number of copies of the virus per millilitre of blood plasma.

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One
Hova.

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One
Hova.

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