Understanding HIV.
Living with HIV.

HIV is not the same as AIDS. Even today, you still sometimes hear people say a person is 'AIDS-infected' or has an 'AIDS infection'. Both terms are incorrect as HIV is not the same as AIDS.

When a person becomes infected with HIV, the human immunodeficiency virus, their status will then be HIV-positive or HIV-infected. And although, say, flu-like symptoms may be observed during the first few weeks following infection, the infection often goes unnoticed for long periods because the immune system is mostly able to control HIV infection for several years.

The term AIDS (acquired immune deficiency syndrome) only applies when the body's own immune defences become weak enough for opportunistic infections to occur (e.g. shingles, pneumonia, tuberculosis, and others). The time it takes to reach this stage varies from person to person, but is generally several years. If started early, therapy can help the immune system remain intact and prevent AIDS developing from an HIV infection.

The HI Virus

History and some interesting facts

 

History

HIV (human immunodeficiency virus) was first identified in humans in the 1950s. Awareness of the virus increased at the start of the 1980s when homosexual men initially – closely followed by transfusion patients and haemophiliacs – started to develop more cases of infections, cancers, and other conditions typically associated with AIDS, with those infected generally dying within just a few years.

It is assumed that HIV originates from various monkeys and was transmitted to humans by chance (as a result, for example, of eating monkey flesh ('bush meat') or through bites).

 

 

Interesting facts about viruses

Viruses have no metabolism of their own and all rely on other organisms in order to multiply. Viruses force their way into a host cell and use the resources there in order to multiply. But multiplication does not have to take place immediately as viruses can also simply set up home in host cells and 'sleep' there for decades.

Viruses are classified in various ways: by host organism, the type of genetic material involved (RNA or DNA, double- or single-strand), and other characteristics.

 

HIV is a retrovirus from the Lentivirus family and is pathogenic to humans. 

  • Retroviruses, having made it into the host cell, first have to 'transcribe' their genetic material (then in the form of RNA) so it is in a form (DNA) which can be integrated into the host cell's genetic material. The virus brings with it the enzymes required for this purpose (reverse transcriptase, integrase, and protease).
  • Lentiviruses (slow viruses) remain in the host organism for life. They are very clever at evading the immune system and tend to cause diseases associated with slow progression.

 

 By virtue of these properties, HIV is different from other viruses pathogenic to humans, such as cold viruses (these are not integrated into the host cell's genetic material, and colds start within just a few days of infection) or herpes viruses (long-term infections, although herpes viruses are not integrated into the host cell's genetic material). 

 

Epidemiology: HIV worldwide

The HI virus can be found worldwide, with the majority of those infected living in sub-Saharan Africa (some 25 million adults and children). 

The Federal Office of Public Health FOPH estimates there are currently between 13 000 und 20 000 people with HIV in Switzerland who actually know they are infected. Then there are further several hundred people who are not aware they are infected with HIV.

 

Around 500 new cases of HIV are diagnosed each year, of which 30-50% are late diagnoses where immunodeficiency is already advanced. Earlier diagnosis and therefore an earlier start for therapy could improve life expectancy for the person concerned – and both could also reduce the number of new infections.

 

The immune system

Duties of the immune system

The immune system is the body's own defence system and protects the human body against things like bacteria, viruses, fungi, and parasites. Most of the work involved is done by the various groups of white blood cells. These circulate in the blood and lymph vessels and can also be found in various tissues. 

 

Which cells are involved in HIV infection?

 

Killer cells and scavenger cells:

Killer cells (NK cells) are part of our innate immune defences and are able to identify foreign bodies and pathogens directly and eliminate them. Together with scavenger cells, they form the first line of defence against infections. Scavenger cells (macrophages) are mainly found in tissue, where they are able to 'scavenge' for any pathogens that may have infiltrated and subsequently alert and activate T helper cells (part of the acquired immune system) by presenting antigens associated with the (scavenged) pathogens on their surface.

 

Lymphocytes or B cells:

Once activated, B cells, also known as B lymphocytes (the B stands for bone marrow, where these cells are formed), mark pathogens with antibodies so these can be identified by other cells belonging to the immune system. The antibodies produced by B cells are highly specific and only bind a certain type of antigen in each case.

 

T lymphocytes or T cells:

T lymphocytes (the T stands for thymus, where these cells are formed) include T helper cells, regulatory T cells, and cytotoxic T cells. In terms of immune defences against HIV, T helper cells (or CD4 helper cells), which are responsible for coordinating the immune response, are particularly important. T cells carry the so-called T cell receptor on their surface, which enables each cell to recognise its specific antigen based on the lock-and-key principle. This needs to be present on the surface of the body's own cells.

CD4 helper cells 'control' the activities of the immune system by both strengthening general immune defences and stimulating production of specific antibodies. If they are absent or significantly reduced in number the body's own defences will be weakened, which may see ordinarily harmless pathogens lead to potentially lethal infections (opportunistic infections).

HIV infection

History and some interesting facts

 

The course of HIV infection

 

Infection of target cells

HIV mainly attacks the CD4+ helper cells within the immune system. Once cells have been infiltrated, the viral genetic material is transcribed with the help of the reverse transcriptase (the RNA is transcribed into double-strand DNA) so it can integrate into the host cell's genetic material. Integrase – another enzyme which HIV brings with it – is responsible for this step. If HIV has infected active cells, multiplication commences immediately and the host cell is destroyed; if resting cells have been infected, multiplication of the virus and host cell death only occur following activation.

Protease (another viral enzyme) is required in order to create functional and therefore infectious viruses from the proteins created by the host cell.

Acute and chronic phase of HIV infection

As soon as the HI virus has integrated into the host cells, the person in question is infected with HIV. And although, say, flu-like symptoms may be observed during the first few weeks following infection (acute phase), the infection often goes unnoticed for long periods because the immune system is mostly able to control HIV for several years. During this time, there is a certain balance between HI viruses and CD4 helper cells (chronic phase).

As the infection progresses, the number of CD4+ helper cells slowly but steadily declines until the immune system is 'depleted' and the virus has the upper hand.

AIDS

The term AIDS (acquired immune deficiency syndrome) applies when the body's own immune defences become weak enough – because, say, the number of CD4 helper cells has declined – for opportunistic infections to occur (e.g. shingles, pneumonia, tuberculosis, and others). The time it takes to reach this stage varies from person to person, but is generally several years. If started early, therapy can help the immune system remain intact and prevent AIDS developing from an HIV infection.

Life expectancy

HIV infection remains incurable, although it has become more of a chronic condition over the past 30 years, and one which is highly amenable to treatment. Particularly if infection is detected early and therapy begins in good time, life expectancy will be about the same as for the general population – despite the infection.

 

How high is the risk of infection?

Social contact through things like kissing, shaking hands, or using the same objects (glasses, crockery, cutlery, or even the toilet) is harmless. The highest level of risk is associated with unprotected sex with an HIV-positive partner taking no HIV therapy and with sharing needles when 'slamming' or getting a 'fix'.

HIV can mainly be found in blood, sperm, vaginal fluid, maternal milk, and the liquid film covering mucous membranes (e.g. in the vagina, on the penis, or the intestinal mucosa). Those infected with HIV who take their HIV therapy regularly and whose blood shows an undetectable viral load are unlikely to infect a sexual partner, even during sex without a condom. 

However, sexual contact with people infected with HIV but not receiving treatment does carry a risk of HIV infection, and this risk is highest during receptive anal sex. The rate here is 50 HIV infections for every 10,000 contacts. Further examples are listed in the table below:

HIV therapy

HIV is not curable, but is amenable to therapy

 

HIV infection remains incurable, although it has become more of a chronic condition over the past 30 years, and one which is highly amenable to treatment. Particularly if infection is detected early and therapy begins in good time, life expectancy will be about the same as for the general population – despite the infection.

Thanks to studies and data gathered from day-to-day clinical practice, we now know that antiretroviral therapy should begin as early as possible – i.e. preferably within a few weeks of diagnosis. The advantage with this approach is that the immune system is largely preserved, with the risk of developing AIDS or other complications remaining low. These days, all the relevant therapy guidelines recommend starting therapy early.

Starting therapy early not only promises near-normal life expectancy, but also currently means a person will need to take tablets every day for the rest of their life. It is important people are absolutely clear about this before starting therapy. So far, the possibility of a cure remains elusive.

A key reason why life-long therapy is required is the fact that HIV also infects 'sleeping' immune cells (CD4 cells, macrophages, and dendritic cells) and then only becomes activated or infectious when the host cell becomes active too. 

Another reason is that although some organs and cells are easy for medicines to reach, there are others where some medicines find it harder or even impossible to penetrate – such as the brain or genital tract.

 

This means the most important objectives in terms of modern HIV therapy are:   

  • Keeping the viral load as low as possible (no evidence of the virus) in the whole body
  • Keeping the number of CD4 helper cells as high as possible.

 

Investigations at the start of therapy

To ensure therapy is 'right' from the very start, it is a good idea – besides determining the CD4 cell count and measuring the viral load – to perform a number of investigations before commencing, such as a resistance test (genotyping). This will ensure that the preferred therapy is effective too and should be performed as early as possible (preferably straight after HIV diagnosis). It also maximises the chances of discovering any infection with a resistant HI virus and makes it possible to adapt the therapy accordingly.

 

Modern HIV therapy is a combination therapy

HIV therapy – also referred to as antiretroviral therapy (ART for short) or sometimes even HAART (highly active antiretroviral therapy) or cART (combination antiretroviral therapy) – currently takes the form, as a rule, of a combination therapy with medicines from various classes of active ingredients. The thinking behind this is to attack different points important to viral multiplication – at the same time – and thereby minimise the probability the virus will 'escape'. As such, the only successful way of suppressing viral multiplication over the long term is to base therapy on a combination of several medicines from different classes with different mechanisms of action. Three medicines from different classes are combined as a rule. The decision regarding which medicines to use is made on a case-by-case basis.

The most important classes of active ingredients are NRTIs (nucleoside reverse transcriptase inhibitors), NNRTIs (non-nucleoside reverse transcriptase inhibitors), INIs (integrase inhibitors), and PIs (protease inhibitors). Therapy has been made easier in the last 20 years with the development of combination therapies. Often, it only takes one tablet a day to keep the virus in check.

 

Reverse transcriptase inhibitors (NRTIs or NNRTIs) inhibit the virus's own enzyme known as reverse transcriptase, which is responsible for transcribing the viral genetic material. Here, the copying process required for the viral genetic material to integrate into the human cell is interrupted. Another enzyme belonging to the HI virus, known as integrase, is also responsible for integration of the viral genetic material. Integrase inhibitors can stop integration taking place. Ideally therefore, NRTIs, NNRTIs, and INIs can prevent long-term infection of the host cell. Protease inhibitors (PIs) take effect in cells already infected and ensure HIV protease is unable to cut the various viral proteins properly.  This means no infectious new viruses are created.

How frequent are side effects?

Side effects can occur with any medicine, of course, but modern HIV medicines are far easier to tolerate than their precursors, which paved the way for antiretroviral therapy in the 1990s.

Side effects can vary significantly, and people may experience them in very different ways too. What one person might find to be a minor irritation may prove unacceptable to someone else. Given there are now so many different antiretroviral medicines, it is possible in many cases to switch therapy – although the patient must inform their doctor of any side effects. The important thing is that the therapy must suit the patient as this is the only way to ensure medicines will be taken consistently.

 

Why is it important to think about interactions?

It is important that patients think about possible interactions as – besides other prescription medicines – herbal preparations, over-the-counter medicines, recreational drugs, and multi-vitamin preparations may also interact with HIV therapy. Typical examples include St John's wort or medicines taken for stomach complaints. 

Interactions may change (increase or decrease) the effective level of any medicines or recreational drugs taken. If the concentrations of active ingredients rise, this may result in side effects – if concentrations fall too low, the medicines may no longer work.

It is important therefore that people inform their doctor about any substances they are taking or injecting with a view to avoiding any unnecessary risks.

 

Monitoring therapy

To monitor whether HIV therapy is working, it is a case of determining the viral load (number of viruses in the blood) and the CD4 cell count (the state of the immune system).

If therapy is working well, the viral load should be below 50 virus copies per millilitre of blood and the CD4 cell count should recover until the normal range (500-1,400 cells per microlitre of blood) has been reached.

Both values are measured every 3 months or so, when starting or switching therapy, or more often.

There are also other investigations to determine whether renal function and liver values are normal and that blood lipids are not too high.