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All about HIV

HIV is a virus which is most commonly passed on by sexual contact. HIV attacks cells of the immune system. Untreated, the immune system weakens so that the body cannot defend against various bacteria, viruses and other germs. This is when AIDS (commonly now called late-stage HIV infection) develops. However, early detection and treatment with antiretroviral therapy (ART) means that people living with HIV can lead active, healthy lives, although they may get side-effects from the treatment.

What are HIV and AIDS?

HIV stands for human immunodeficiency virus. This is a virus in the group of viruses called retroviruses. HIV destroys cells in the body called CD4 T cells. CD4 T cells are a type of lymphocyte (a white blood cell). These are important cells involved in protecting the body against various bacteria, viruses and other germs. HIV actually multiplies within CD4 cells. HIV cannot be destroyed by white blood cells, as it keeps on changing its outer coat, so protecting itself.

AIDS stands for acquired immunodeficiency syndrome. This is a term which covers the range of infections and illnesses which can result from a weakened immune system caused by HIV. Because ART has altered the way we think about the condition, the term late-stage HIV is being increasingly used instead of AIDS.

Note: HIV and AIDS are not the same thing and people who get HIV infection do not automatically develop AIDS. AIDS is unlikely to develop in people who have been treated in the early stages of HIV infection. Even in people who do not receive treatment, there is usually a time lag of several years between first being infected with HIV and then developing infections and other AIDS-related problems. This is because it usually takes several years for the number of CD4 T cells to reduce to a level where your immune system is weakened.

People with HIV can pass the virus on to others whether or not they have any symptoms.

How do you become infected with HIV?

Sexual transmission. This is the most common way to pass the virus on. In 2010, it accounted for about 19 in 20 new confirmed cases in the UK. Semen, vaginal secretions and blood from an infected person contain HIV. The virus can enter the body through the lining of the vagina, vulva, penis, rectum or mouth during sex. Having vaginal or anal sex with an infected person is the most common route. Oral sex carries a much lower risk but this can increase if you have a condition which affects the defence barriers of the mouth, such as ulcers, bleeding or damaged gums or a sore throat. You cannot be infected with HIV by coming into contact with the saliva of an infected person (for example, through kissing or coming into contact with spit). HIV is not passed on by coughing or sneezing.
Needle sharing. HIV (and other viruses such as hepatitis B and hepatitis C) can be passed on by people who are dependent on injectable drugs and share needles, syringes and other injecting equipment which is contaminated with infected blood. However, needle-exchange services run by hospital, clinics and drug dependency units and the more ready availability of medicines taken by mouth (such as methadone) have drastically reduced needle-sharing as a source of infection.
Infected blood. In the past, quite a number of cases occurred from infected blood transfusions and other blood products. This is now rare in the UK, as since 1985 all blood products are checked for HIV before being used. It is still a significant problem in developing countries.
Accidental needlestick injuries. There have been no cases of HIV infection from needlestick injuries in a healthcare setting in the UK since 1999. HIV infection from a needlestick injury outside of a healthcare setting has never been recorded anywhere in the world.
From mother to child. HIV can be passed to an unborn child from an HIV-positive mother. However, with appropriate treatment the risk of transmission of HIV from mother to baby can be reduced to less than 1 in 100. This means that, with appropriate treatment, the vast majority of babies born to HIV-positive mothers will not have HIV. Achieving this depends on detecting HIV before pregnancy, or, in early pregnancy, when anti-medicines can be taken by the mother. Having a Caesarean section to deliver the baby reduces the risk even further. HIV can occasionally be passed to babies through breast milk during breast-feeding. If formula milk is available, mothers with HIV are encouraged not to breast-feed.
Note: to become infected with HIV, some infected blood, semen or vaginal secretions would have to get into your body. You can not catch HIV from ordinary contact with someone with HIV, such as hugging, shaking hands or touching, or from sharing food, towels, utensils, swimming pools or telephones.

How common is HIV?

The number of new people diagnosed with HIV in the UK peaked at 8,000 in 2006 and dropped to 6,660 in 2010. The total number of people living with HIV in the UK in 2010 was 91,500. Of these, About 9 in 20 resulted from men having sex with men and about 9 in 20 were due to heterosexual sex. HIV infection is much more common in many other countries in the world.

How does HIV cause problems in the body?

Once HIV is in your body the virus attaches to and gets into the CD4 T cells. The virus then uses the DNA (the genetic code inside the cell) to replicate (make copies of itself). As new virus particles break out of a CD4 T cell, the cell dies. The new virus particles then attach and enter new CD4 T cells and so the process continues. Millions of new virus particles are made in CD4 T cells each day and millions of CD4 T cells die each day.

To counter the virus destruction the body continues to make new CD4 T cells each day. However, over time, the virus usually wins and the the number of CD4 T cells gradually falls (usually over several years). Once the level of CD4 T cells goes below a certain level, your immune system is weakened. If your immune system is severely weakened by HIV infection then you are likely to develop various opportunistic infections. These are infections caused by germs which are commonly around us. You would not normally develop infections from these germs if you have a healthy immune system. A low level of CD4 T cells also increases the risk of developing other conditions which the immune system helps to prevent such as certain cancers.

What are the symptoms of HIV and AIDS?

Primary infection with HIV
When you first become infected with HIV it is known as the primary infection. About 8 in 10 people develop symptoms at this time. The three most common symptoms (sometimes known as the classic triad) are sore throat, fever and a blotchy red rash. Other symptoms can include feeling sick, diarrhoea, swollen glands, headache, tiredness and general aches and pains. The symptoms can last up to three weeks and are often just thought of as flu or a mild viral illness.

After the primary infection
After any primary infection settles, you can remain without any symptoms for several years. Early testing and treatment has revolutionised our concept of HIV infection which is now considered a long-term disease (see ‘What is the prognosis (outlook)?’, below). Even without treatment, there are often no symptoms for a long time (often up to ten years) and many people do not realise that they are even infected. However, the virus continues to multiply, the number of CD4 T cells tends to gradually fall and you can pass on the virus to others. During this time some people with HIV who are otherwise well may develop persistent swollen lymph glands (persistent generalised lymphadenopathy) or night sweats.

In time you may start to develop problems such as recurring mouth ulcers, recurring herpes or shingles infections, or seborrhoeic dermatitis (a skin condition caused by a yeast). Old tuberculosis (TB) infection may reactivate in some cases even before AIDS develops, especially in people in the developing world. Other symptoms of HIV that may occur before AIDS develops include diarrhoea, skin rashes, tiredness and loss of weight.

Symptoms of AIDS
The term AIDS is used to describe the most advanced stages of HIV infection and is being overtaken by the term late-stage HIV. People who are treated early in an HIV infection do not develop this stage. AIDS is a general term which includes various diseases which can result from a very weakened immune system. Typically, a person with AIDS has:

A very low level of CD4 T cells (around 200 cells per cubic millimetre of blood or below), and/or
One or more opportunistic infections such as Pneumocystis jirovecii pneumonia, severe thrush in the vagina or mouth, fungal infections, TB, Mycobacterium avium complex, toxoplasmosis, cytomegalovirus, etc. These infections can cause a range of symptoms including sweats, fever, cough, diarrhoea, weight loss and generally feeling unwell.
In addition, people with AIDS have an increased risk of developing other conditions such as:

Certain cancers. Kaposi’s sarcoma is a cancer which is usually only seen in people with AIDS. There is also an increased risk of developing cancer of the cervix and lymphoma.
An AIDS-related brain illness such as HIV encephalopathy (AIDS dementia).
A severe body wasting syndrome.
Many different symptoms can develop from the above conditions. Children with AIDS can develop the same opportunistic infections and problems as adults. In addition, they may also develop severe common infections of childhood such as severe ear infections or severe tonsillitis.

What tests are done?

Most sexual health clinics offer a rapid blood test for HIV and can give results within thirty minutes. Even if rapid testing is not available, the results are usually back within a week. Modern tests will pick up the infection a month after first being infected (as opposed to three months with the older tests). GPs can also arrange blood tests but the result will go on your health record. It is recommended that all gay and bisexual men should be tested every year, more often if they have anal sex without a condom, multiple partners, have been diagnosed with another sexually-transmitted disease or develop symptoms of primary or late-stage HIV.

Assessing the extent of disease
If you are confirmed to have HIV then your doctor may do a blood test to check the amount of virus in your blood (the viral load) and the number of CD4 T cells in your blood. These tests may be done from time to time to assess how far the disease has progressed (and the response to treatment).

Tests to diagnose AIDS-related conditions
There is no test for AIDS but you may have a range of other tests to detect opportunistic infections or other AIDS-related conditions. These will depend on the type of symptoms that you develop.

What is the treatment for HIV infection?

Although there is still no cure for HIV, treatment is now effective at allowing people with HIV to live their lives as normally as possible. Since the introduction of medicines to treat HIV, the death rates from AIDS has reduced dramatically. With effective treatment, very few people go on to develop AIDS.

It is not uncommon for people with HIV to feel low or even depressed, especially soon after the diagnosis is made. If you have any feelings of depression then you should speak to your doctor.

Treatment to tackle the virus itself
HIV is now a treatable medical condition and most people with the virus remain fit and well on treatment. Since the 1990s a number of medicines have been developed called antiretroviral medicines. Antiretroviral medicines work against HIV infection by slowing down the replication of the virus in the body. Newer medicines are more effective than medicines used in the past. There are several classes of these medicines which include: nucleoside reverse transcriptase inhibitors (NRTIs), nucleotide reverse transcriptase inhibitors (NtRTIs), protease inhibitors (PIs) and non-nucleoside reverse transcriptase inhibitors (NNRTIs). Newer classes of medicines have recently been introduced which are integrase inhibitors, fusion inhibitors and CCR5 antagonists. The medicines in each class work in different ways but all work to stop the HIV from replicating itself. This method of treatment is called antiretroviral therapy (ART). You may still occasionally see this referred to as highly active antiretroviral therapy or HAART.

There is a growing body of evidence that taking ART reduces the risk of passing the HIV infection on to others.

Taking three or more antiretroviral medicines at the same time, each attacking HIV at different points in its cycle of replication, is more effective than one or two medicines alone. Taking a combination of different medicines also reduces the risk that the virus will become resistant to any individual medicine. In 2008 the first one pill a day treatment was launched. Each pill contains three different medicines. This is popular, as it is convenient to take and has few side-effects.

The choice of medicines is considered and chosen for each individual patient. The treatment for HIV can be complicated but the majority of people diagnosed with HIV now take anti-retroviral treatment in a combination-format just once or twice a day. A team of healthcare professionals is usually involved in looking after you and giving you your treatment.

The aim of treatment is to reduce the viral load to low levels. In most people who are treated with ART, the viral load reduces to very low levels and the number of CD4 T cells rises. This means your immune system is no longer as weakened and you are not likely to develop opportunistic infections. However, it is vital to take the medication regularly and exactly as prescribed to maintain success, and to help to prevent the virus from becoming resistant to the medicines.

As with other powerful medicines, antiretroviral medicines can cause side-effects in some cases. In addition, some of these medicines can react with other commonly used medications. It may be necessary to change an initial combination of medicines to a different combination because of problems with side-effects, reactions or resistance of the virus to an initial medicine. Therefore, different people with HIV can often take different combinations of medicines. Common side-effects include nausea, vomiting and headaches.

When is treatment with antiretroviral medicines started?
As a general rule, antiretroviral medicines are usually started if:

Your CD4 T cells fall below a certain level (around 350 cells per cubic millimetre of blood or less) – even without symptoms. The exact level when treatment is started depends on various factors which your doctor will discuss with you. These include any symptoms present and the rate of decline of the CD4 T cells.
Opportunistic infections or other AIDS-related problems develop.
However, the treatment of HIV is a rapidly changing area of medicine. Trials are underway to assess whether antiretroviral medicines should be started earlier in people who have no symptoms, even as early as when first infected with HIV. The trials aim to show whether there are benefits from treatment before symptoms develop, which outweigh the risk of side-effects from the medicines. You are likely to have regular blood tests to monitor for side-effects whilst taking treatment.

Treatment and prevention of infections
Wearing a condom when having sex is very important to protect against other sexually transmitted infections, including herpes and hepatitis. People with HIV are usually vaccinated against hepatitis A and hepatitis B, influenza and the pneumococcus (a common cause of pneumonia).

Opportunistic infections are usually treated with antibiotics, antifungals or anti-TB medicines, obviously depending on which infection develops. Even if you have not developed an infection, once the CD4 T cells fall to a low level, you will normally be advised to take a regular dose of one or more antibiotics or other medicines to prevent certain opportunistic infections from developing.

How can infection with HIV be prevented?

There is no vaccine to prevent HIV. Development of one is proving to be very difficult, as the HIV virus is constantly mutating and changing. Therefore, the main way to prevent infection by HIV is to avoid activities that put you at risk, such as sharing needles and having sex without a condom.

Some cases of HIV can be prevented in other ways – for example:

If you are an injecting drug user then do not share needles or other injecting equipment. If available, use local needle exchange schemes.
If you think they have been exposed to HIV through sharing needles or sexual contact you should contact your GP or a sexual health clinic as soon as possible. If it is thought that there is a high risk that you may pick up the infection you will be offered a course of anti-HIV medicines. These are most effective when taken as soon as possible after exposure and certainly within 72 hours.
Healthcare workers should follow local guidelines to reduce the chance of needlestick injury. If you do have an injury, see your occupational health specialist urgently. A course of anti-HIV medicines started as soon as possible and no later than 72 hours after the injury may prevent infection with HIV developing.
If you are pregnant and have HIV infection then you need special antenatal care to reduce the risk of passing on the virus to your baby. HIV treatments can be taken during pregnancy. An HIV test is offered to all pregnant women in the UK.
What is the prognosis (outlook)?

People with HIV who are diagnosed in good time can expect to lead a near-normal lifespan. A study to predict the life-expectancy of men infected with HIV at 30 years of age in 2010 found that they could expect to live to 75, based on access to current treatments. Those who are diagnosed late (with a CD4 count below 350 – the point at which treatment should commence), are more likely to have a poor prognosis. However, even when someone has been diagnosed with a low CD4 count, treatment can effectively bring them back to a good level of health. Life expectancy also depends on other factors such as smoking, alcohol intake and use of other medicines.

In short – for people who have access to modern medicines, the outlook (prognosis) has improved greatly in recent years.

Further help and information

HIV aware
Web: http://www.hivaware.org.uk
Developed by NAT, the website provides all the basic facts about HIV plus additional information and real stories from people living with HIV.

National Aids Trust
New City Cloisters, 196 Old Street, London, EC1V 9FR
Tel: 020 7814 6767 Web: http://www.nat.org.uk
Aims to promote a wider understanding of HIV and AIDS, develop and support efforts to prevent the spread of HIV and improve the quality of life of people affected by HIV and AIDS.

Terrence Higgins Trust
314-320 Grays Inn Road, London, WC1X 8DP and various offices around the country (see website)
Tel: 0808 802 1221 for an adviser or 020 7812 1600 for switchboard Web: http://www.tht.org.uk
A national HIV and sexual health charity. Their helpline offers information and support to anyone living with HIV, affected by HIV indirectly or concerned about their sexual health.Once you’re infected with the HIV virus, it most commonly attacks your T-cells, which are also known as CD4 cells. When one of these cells is infected, and if it is untreated, it goes through several steps to reproduce and copy itself to create more of the virus.

The HIV life cycle process is commonly broken up into the following steps:

Binding and Fusion:

This is the process by which HIV binds to a specific type of CD4 receptor (a protein present on the outside of infection-fighting white blood cells, CD4 receptors allow HIV to fuse to and enter cells) and one of two co-receptors (another protein, one known as CCR5 and the other known as CXCR4) on the surface of the CD4 cell. Once this occurs, HIV can fuse with the host cell (CD4 cell) and release its genetic material, its RNA, into the host cell.

HIV drugs that are used to block this particular step are called Entry Inhibitors. Entry Inhibitors work by preventing HIV from entering healthy T-cells. There are currently two FDA approved Entry and Fusion Inhibitors – Selzentry and Fuzeon.

Reverse Transcription:

An enzyme called Reverse Transcriptase changes the genetic material of the virus (from single-stranded HIV RNA to double-stranded HIV DNA) so it can be integrated into the host DNA.
This Reverse Transcription process can be blocked by two HIV drug categories: Nucleoside Reverse Transcriptase Inhibitors (NRTIs or Nukes) and Non-Nucleoside Reverse Transcriptase Inhibitors (NNRTIs or Non-Nukes).

There are currently 7-different NRTIs approved for use by the FDA, two of which are considered “Preferred” – Emtriva and Viread.

Four different NNRTIs are approved by the FDA. The “Preferred” drug in this category is Sustiva.

The drugs in these two categories are also co-formulated with drugs from other HIV-fighting categories in single-pill regimens such as Atripla, Complera and Stribild or combination pill regimens like Truvada.

Integration:

The virus’ new genetic material enters the nucleus of the CD4 cell and uses an enzyme called Integrase to integrate itself into the host cell’s own genetic material, DNA, where it may “hide” and stay inactive for several years producing few or even no new copies. This integrated HIV DNA is called Provirus.

The drugs in this HIV drug category that are meant to stop this process are called Integrase Inhibitors. Isentress is “Preferred” by the FDA but 2 new drugs are awaiting approval in this category – one of which, Elvitegravir, is already present in single pill, once-daily Stribild.

Transcription:

When the host cell receives a signal to become active, the provirus uses a host enzyme called RNA polymerase to create copies of the HIV genetic material and shorter strands of RNA called messenger RNA (mRNA). The mRNA is used as a blueprint to make long chains of HIV proteins.

Assembly:

An enzyme called Protease cuts the longer HIV proteins into individual proteins. As the smaller HIV proteins come together with copies of HIV’s RNA genetic material, a new virus particle is assembled.

This viral assembly can be blocked with the HIV drug category called Protease Inhibitors. There are currently 8-drugs approved by the FDA in this category. Reyataz and Prezista are listed as “Preferred” in this category.

Budding:

This is the final stage of the virus’ life cycle. The virus pushes itself out of the host cell, creating “buds,” taking with it part of the membrane of the cell. This outer part covers the virus and is covered with protein/sugar combinations called HIV glycoproteins. These HIV glycoproteins are necessary for the virus to bind CD4 and co-receptors. The new copies of HIV can now move to infect other cells.

STAGES OF HIV

The HIV virus has a progression. It’s important to understand that if you are infected with HIV, you don’t have Acquired Immune Deficiency Syndrome (AIDS). However, if you don’t get treatment, HIV will eventually overtake your immune system—and this will lead to your being diagnosed with AIDS. Here are the common stages of untreated HIV:

Acute Infection:

Within 2-4 weeks after being infected with HIV, you can experience an acute illness that can often feel like severe flu symptoms. This is called Acute Retroviral Syndrome (ARS) or Primary HIV Infection and it’s the body’s natural natural response to fighting the HIV infection. According to the U.S. Department of Health and Human Services, not everyone develops ARS and it can take up to 3 months for it to appear in some people.

During this period of infection, large amounts of virus are being produced. The virus uses CD4 cells to replicate and destroys them in the process. Because of this the CD4 count can fall rapidly. Eventually the immune response will begin to bring the level of virus back down to a level called a Viral Set Point, which is a relatively stable level of the virus. At this point, the CD4 count begins to increase, but it may not return to pre-infection levels.

Clinical Latency:

After the acute stage of HIV infection, the disease moves into a stage called Clinical Latency. This period is also called Asymptomatic HIV Infection or Chronic HIV Infection. During this stage, HIV reproduces at very low levels, although it is still active. An undetectable viral load and a healthy CD4 cell count may be maintained during the earlier years of this phase. There may not be symptoms. This period can last up to 8 years or longer.

While some people progress through this phase faster than others, it is important to remember that HIV is still able to be transmitted to others during this phase.
Toward the middle and end of this stage, the viral load will begin to rise and the CD4 cell count will begin to drop. When this happens, their may be constitutional symptoms of HIV (fever, night sweats, weight loss and fatigue) as the virus levels increase.

AIDS:

If the number of CD4 cells falls below 200 cells per cubic millimeter of blood or an opportunistic infection is developed, a person is considered to have AIDS. A normal CD4 count is between 500 and 1,600 cells/mm3. This is the stage of infection that occurs when your immune system is badly damaged and you become vulnerable to opportunistic infections. At this stage, it is important to know that treatment is still absolutely possible yet extremely urgent.

Aidsmap website
Web: http://www.aidsmap.com
A comprehensive web-based resource on matters relating to HIV and AIDS.

Averting AIDS and HIV (AVERT)
Web: http://www.avert.org
An international HIV and AIDS charity with lots of useful information on its website.
Tel: 01403 210202 or email info@avert.org.

References | Provide feedback
Original Author: Dr Tim Kenny Current Version: Dr Laurence Knott Peer Reviewer: Dr John Cox
Last Checked: 15/03/2012 Document ID: 4832 Version: 39 © EMIS
Disclaimer: This article is for information only and should not be used for the diagnosis or treatment of medical conditions. EMIS has used all reasonable care in compiling the information but make no warranty as to its accuracy. Consult a doctor or other health care professional for diagnosis and treatment of medical conditions. For details see our conditions.

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