Treatment

 

Main principles of treatment

What is HIV antiretroviral treatment?

This is the main type of treatment for HIV or AIDS. It is not a cure, but it can stop people from becoming ill for many years. The treatment consists of drugs that have to be taken every day for the rest of someone's life.

HIV is a virus and like other viruses when it is in a cell in the body it produces new copies of itself. With these new copies, HIV can go and infect other previously healthy cells. It is easy for HIV to spread quickly through the billions of cells in the body if it is not stopped from replicating.

Antiretroviral treatment for HIV infection consists of drugs which work against HIV infection itself by slowing down the replication of HIV in the body. The drugs are often referred as:

antiretrovirals;

anti-HIV drugs;

HIV antiviral drugs.

What is Combination Therapy, what is HAART?

For antiretroviral treatment to be effective for a long time, it has been found that you need to take more than one antiretroviral drug at a time. This is what is known as Combination Therapy. The term Highly Active Antiretroviral Therapy (HAART) is used to describe a combination of three or more anti-HIV drugs.

When HIV replicates it often makes mistakes. This means that within any infected person there are many different strains of virus. Occasionally, a new strain is produced that happens to be resistant to the effects of an antiretroviral drug. If the person is not taking any other type of drug then the resistant strain is able to replicate quickly and the benefits of treatment are lost.

Taking two or more antiretrovirals at the same time vastly reduces the rate at which resistance develops.

The Treatment of Opportunistic Infections

When a person's immune system is damaged by HIV, then certain infections or cancers will develop which the body would normally "fight off" quite easily. These are known as Opportunistic Infections. Treatment for Opportunistic Infections is usually provided when antiretrovirals are not available, or when the antiretrovirals drugs are no longer effective as the person is resistant to them.

The Groups of Antiretroviral Drugs

There are four main groups of anti-HIV drugs. Each of these groups attacks HIV in a different way.

Nucleoside/Nucleotide Reverse Transcriptase Inhibitors

The first group of antiretroviral drugs are the Nucleoside/Nucleotide Reverse Transcriptase Inhibitors (NRTIs). These were the first type of drug available to treat HIV infection in 1987 and are better known as nucleoside analogues or nukes. (Note: the difference between "nucleotide" and "nucleoside" is rather subtle; tenofovir is the only currently approved nucleotide RTI).

Once it has entered a human cell, HIV uses an enzyme called reverse transcriptase to begin the process of replication. The enzyme is used to make a DNA copy of the virus RNA (genetic material), which acts as the blueprint for producing components of new viruses. But NRTIs make sure that the DNA copy is faulty, so the process of HIV replication cannot continue. NRTIs are sometimes called the "backbone" of combination therapy because most regimens contain at least two of these drugs.

Non-Nucleoside Reverse Transcriptase Inhibitors

The second group of antiretroviral drugs are the Non-Nucleoside Reverse Transcriptase Inhibitors (NNRTIs). These drugs started to be approved in 1997 and are generally referred as non-nucleosides or non-nukes.

Like the nukes, NNRTIs stop HIV from replicating within cells by intefering with the reverse transcription process. They do this by inhibiting the action of the enzyme reverse transciptase.

Protease Inhibitors

The third type of antiretrovirals is the Protease Inhibitor (PI) group. They were first approved in 1995. Protease inhibitors, as the name says, inhibit protease. Almost every living cell contains some type of protease, which is a digestive enzyme that breaks down proteins.

In the final stages of HIV replication, the infected human cell produces long chains of viral proteins. These must be cut up into smaller pieces from which to construct the cores of mature virus particles. Protease inhibitors prevent a special type of HIV protease from carrying out this process, and so prevent the production of mature, infectious virus particles.

Fusion or Entry Inhibitors

The fourth group of antiretrovirals is comprised of Entry Inhibitors, including Fusion Inhibitors. One of these drugs - commonly called T-20 - has been licensed both in the US and in Europe since 2003, but only for use by people who have already tried other treatments. The T-20 fusion inhibitor differs from the other antiretrovirals in that it needs to be injected (otherwise it would be digested in the stomach).

In order to enter a human cell, HIV must first attach itself to the cell's surface and then fuse its envelope with the cell's membrane. The attachment process typically involves the binding of an HIV surface protein called gp120 with a human cell surface protein called CD4, and the fusion process involves an HIV surface protein called gp41. Entry inhibitors interfere with these proteins. For example, T-20 sticks to gp41 to prevent fusion. So unlike the three other classes of drugs, entry inhibitors act against HIV before it has entered a cell.

The names of antiretroviral drugs

There are currently more than 20 approved antiretroviral drugs in the UK (including combined formulations) and many more in the expanded access programmes and trials. Most antiretroviral drugs have at least three names.

Sometimes a drugs is referred to by its research or chemical name, such as AZT. The second name for the drug is the common name for all the drugs with the same chemical structure, for example AZT is also known as zidovudine. The third name is the brand name given by the pharmaceutical company; one of the brand names for zidovudine is Retrovir. Lastly, an abbreviation of the common name might sometimes also be used, such as ZDV, which is the fourth name given to zidovudine.

Nucleoside/Nucleotide Reverse Transcriptase Inhibitors (NRTIs):

Combined NRTIs:

Non-Nucleoside Reverse Transcriptase Inhibitors (NNRTIs):

Protease Inhibitors (PIs):

Fusion or Entry Inhibitors: