HIV+AIDS OVERVIEW

1. human immunodeficiency virus (HIV)

HIV is a retrovirus originally isolated in May 1983 by Luc Montagnier of the Pasteur Institute, Paris.

Retroviruses are unusual in that they copy their genetic material (RNA) onto the genetic material of a person ’ s own cell (DNA). HIV prevents the immune system from fighting infection and is able to infect CD4 cells that coordinate the immune system ’ s fight against infection. HIV will also infect cells in the brain and gut.

Infected cells are either destroyed or will no longer work properly. Basically, HIV-infected cells then become virtual HIV factories making thousands of copies of HIV instead of copies of the CD4 cell itself. When the new HIV copies are made they break down the cell wall, the infected cell is destroyed and HIV will then infect new cells.

2. acquired immune deficiency syndrome (AIDS)

AIDS is the result of the depletion of the specific immune cells (CD4 cells), caused by HIV.

Unlike most illnesses, AIDS is not characterised by a set of common symptoms. It is the result of damage to the immune system, the resultant deficiency in the immune function allowing certain specific opportunistic infections or tumours to flourish. A combination of infections with other markers of illness (such as weight loss, diarrhoea etc) can give a diagnosis of AIDS. Some opportunistic infections are, on their own, AIDS-defining as they very rarely affect someone who is not HIV positive (for example, Kaposi ’ s Sarcoma, Cryptoccal meningitis).

3. opportunistic infections (OIs) and cancers  

HIV is a slow-to-medium-acting virus that typically takes a number of years to produce illness in an infected person, in contrast to most viruses that cause disease in a matter of days or weeks.

Over the time during which an HIV positive person ’ s immune defences are gradually becoming undermined, various pathogens in the environment and other viruses, bacteria, fungi and parasites - take advantage of this weakness to attack and cause illness of various kinds. This is why the infections and cancers seen in HIV positive individuals are called ‘ opportunistic ’ .

OIs and tumours are normally not disease-causing but they take the opportunity to cause disease in an individual whose immune system has been damaged. Infections are categorised into four main groups: viral, bacterial, protozoal and fungal.

Over the past few years treatment - either direct or prophylactically - for these infections has improved and some individuals are living longer with HIV without being diagnosed with AIDS .

4. the CD4 count

CD4 cells or T-helper cells are white blood cells, which organise the immune systems response to some micro-organisms, including bacteria, fungal infections and viruses. CD4 count is the measurement of the number of CD4 cells, in a cubic millilitre of blood.

HIV can infect CD4 cells and use them to produce more HIV copies. Even if a person infected with HIV may feel well, millions of CD4 cells are infected by HIV and are destroyed each day and millions more CD4 cells are produced to replace them.

The CD4 count can go up and down naturally in response to infections, stress, smoking, exercise, the menstrual cycle, contraceptive pill, the time of day and season of the year. The CD4 count of a person not infected with HIV may lie anywhere between 500 and 1200 cells per cubic millilitre.

A CD4 count between 500 and 200 indicates that some damage to the immune system has occurred.

If the CD4 count drops below 350, or starts falling rapidly, individuals living with HIV may be asked to consider starting antiretroviral therapy (ART).

If the CD4 count falls below 250-200 they may be asked to also consider commencing prophylaxis for opportunistic infections such as PCP.

5. the viral load

Viral load is the term used to describe the amount of HIV particles in the blood of a person living with HIV. The more HIV in the blood, the faster the destruction of the immune system with a more increased risk to the individual of developing opportunistic infections, which may lead to a diagnosis of AIDS.

The viral load test estimates the amount of HIV RNA in a sample of blood; the number is described as copies of HIV RNA per millilitre. The test result can be anything from undetectable (less than 50 copies) up to millions of copies.

CD4 counts together with viral load testing give clinicians an idea of how the illness is progressing. The aim of antiretroviral therapy (ART) is to increase the CD4 count and drop the levels of HIV RNA in the blood to levels that are undetectable.

Viral load measurements can rise and fall naturally. However, if the number of copies remains high over several months or there is a large increase greater than threefold, ART may be considered, changed or stopped.

Undetectable viral load does not mean that the individual is free from HIV but it is an indication that the HIV has been suppressed by ART or the virus is not active. An undetectable viral load is desirable because there is a very low risk of developing AIDS and low risk of developing resistance to ART.

6. antiretroviral drugs (ARVs)

ARVs work by reducing the level of HIV in the blood or preventing damage to the immune system by interrupting the process of HIV replication. These drugs are not a cure for AIDS, but if they work effectively they can prevent ill health and can extend life.

An untreated person with HIV may have millions of HIV particles in every millilitre of blood. The aim of the treatment is to reduce the amount of HIV to very low levels. ARVs initially were given as monotherapy (AZT being the most well known). Today, drugs are used in combination with an individual taking three or more different types of ARVs.   

The four main types of ARVs are:

(i) nucleoside analogue reverse transcriptase inhibitors (NRTIs)

These target the protein called reverse transcriptase, which is used by HIV when it enters a cell to convert itself into viral DNA. These were the first types of drugs available to treat HIV.

Examples of NRTIs:

§   AZT (Zidovudine, Retrovir)

§   ddi (Didanosine, Videx)

§   3TC (Lamivudine, Epivir)

§   d4t (Stavudine, Zerit)

§   Abacavir (Ziagen)

(ii) non-nucleoside analogue reverse transcriptase inhibitors (NNRTIs)

These also target reverse transcriptase. An NNRTI is often taken with two NRTIs as an alternative to a protease inhibitor.

Examples of NNRTIs:

§   Neviripine (Viramune)

§   Efavirenz (Sustiva)

(iii) nucleotide analogues (NtRTIs)

These also work in a similar way to the two above.

Examples of NtRTIs:

§   Tenofovir (Viread)

(iv) protease inhibitors (PIs)

These target a protein called protease that is used to make new HIV from viral material made in the nucleus. In combination with other ARVs, they are very effective treatments for HIV.

Examples of Pis:

§   Lopinavir/Ritonavir (Kaletra)

§   Indinavir (Crixivan)

§   Amprenavir (Agenerase)

§   Ritonavir (Norvir)

§   Saquinavir (Fortovase)