What are Nucleoside/Nucleotide Reverse Transcriptase Inhibitors (NRTIs)?

When HIV infects a CD4 cell in a person's body, it copies its own genetic code into the cell's DNA. The cell is then "programmed" to create new copies of HIV.

HIV's genetic material is in the form of RNA. In order for it to infect CD4 cells, it must first convert its RNA into DNA. HIV's reverse transcriptase enzyme is needed to perform this process.

NRTIs (sometimes called nucleoside analogues or nukes) contain faulty versions of the building blocks (nucleotides) used by reverse transcriptase to convert RNA to DNA. When reverse transcriptase uses these faulty building blocks, the new DNA cannot be built correctly. As a result, HIV's genetic material cannot be incorporated into the healthy genetic material of the cell – this prevents the cell from producing new virus.

While nucleotide analogues are technically different than nucleoside analogues, they act very much the same way. In order for nucleoside analogues to work, they must undergo chemical changes (phosphorylation) to become active in the body. Nucleotide analogues bypass this step, given that they are already chemically activated.

Nucleoside/Nucleotide Reverse Transcriptase Inhibitors (NNRTIs)

NNRTIs (also known as non-nucleosides or non-nukes for short) attach themselves to reverse transcriptase and prevent the enzyme from converting RNA to DNA. As a result, HIV's genetic material cannot be incorporated into the healthy genetic material of the cell – this prevents the cell from producing new virus.

What are Protease Inhibitors (PIs)?

When HIV infects a CD4 cell in a person's body, it copies its own genetic code into the cell's DNA. The cell is then "programmed" to make new HIV genetic material and HIV proteins.

These proteins must be cut up by the HIV protease (a protein-cutting enzyme) to make functional new HIV virus. PIs block the protease enzyme and prevent the cell from performing this action.

It is recommended that PIs be used in combination with at least two other HIV medications to treat HIV infection.

What are Entry Inhibitors (including Fusion Inhibitors)?

Entry Inhibitors work by preventing HIV from entering healthy CD4 cells in the body. They work differently than many other HIV medications, which are active against HIV after it has infected a CD4 cell.

Entry inhibitors work by attaching themselves to proteins on the surface of CD4 cells or proteins on the surface of HIV. In order for HIV to bind to CD4 cells, the proteins on HIV's outer coat must bind to the proteins on the surface of CD4 cells. Entry Inhibitors prevent this from happening. Entry Inhibitors prevent this from happening. Some Entry Inhibitors target the gp120 or gp41 proteins on HIV's surface. Some entry inhibitors target the CD4 protein or the CCR5 or CXCR4 receptors on a CD4 cell's surface. If Entry Inhibitors are successful in blocking these proteins, HIV is unable to bind to the surface of CD4 cells and gain entry into the cells.

In New Zealand. Fuzeon (enfuvirtide, also known as T20) is the only approved medication in this class at present (although other medications in this class are in development).

HIV positive people who have become resistant to PIs, NRTIs, and NNRTIs will likely benefit from Entry or Fusion Inhibitor medications, as they are a different class of medications.

What are Intergrase Inhibitors?

When HIV infects a CD4 cell in a person's body, it copies its own genetic code into the cell's DNA. The cell is then "programmed" to create new copies of HIV.

HIV's genetic material is in the form of RNA. In order for it to infect CD4 cells, it must first convert its RNA into DNA. HIV's reverse transcriptase enzyme is needed to perform this process.  The RNA is thenintegrated into the CD4 cell.

HIV positive people who have become resistant to PIs, NRTIs, and NNRTIs will likely benefit from Integrase Inhibitor medications (especially those who have developed HIV resistance to drugs that target HIV's two other major enzymes, reverse transcriptase and protease), as they are a different class of medication.

Isentress (raltegravir) has been approved for use in New Zealand by Med-Safe and is currently awaiting Pharmac funding.

Side-effects

Current HIV treatments are very effective and there's now good evidence that thanks to anti-HIV medication you can live a healthy and normal life.  Medications have improved dramatically since the introduction of HAART (Highly Active Antiretroviral Treatment) in 1996 and are more powerful, easier to take, and cause fewer side-effects than the older anti-HIV medications.

You may never experience a side-effect, however, every medicine can cause unwanted side-effects in some people.  If you are taking a lot of medications, there is a greater chance you may develop some side-effects.

A lot of side-effects are mild, can be controlled with other medicines, and lessen or even go away over time. There's also a good chance that you may be able to change from the treatment that is causing your side-effect.

Mood and sleep problems

 Many people taking a combination of antiretrovirals may have included the NNRTI efavirenz (Stocrin). The most notable side-effects of the drug, however, are changes in mood and sleep.

Some people taking efavirenz report feeling “spaced out”, dizzy, or experience changes in their mood (including sadness and depression). Sleep disturbances have also been reported by people taking efavirenz; these can include vivid dreams, nightmares and insomnia.

You may not experience these side-effects if you are taking efavirenz, and if they do develop they tend to be mild.  Generally, they go away over time. Taking efavirenz at bedtime helps some people cope with the dizziness the drug can cause. A small number of people find it difficult to cope with these side-effects. Your doctor may be able to prescribe other treatment to help you (for example, antidepressants or sleeping tablets).

Telling your doctor about problems that you are experiencing can also give you an opportunity to discuss other treatment options that may be available to you.

Dizziness, mood and sleep problems have also been reported as rare side-effects of other HIV drugs.

You should always check with your HIV specialist if you are experiencing any side effects from your anti-retroviral medications. Never stop taking them without consulting your HIV specialist; make an appointment as soon as possible to talk to them about your problems.

Treatment adherence

If you do not take your HIV medications as instructed, they may not work effectively.  This may result in an increase in your viral load, a fall in your CD4 cell count and a greater risk of becoming ill because of HIV.

HIV can become resistant to the drugs used to treat it quite quickly. If the level of an anti-HIV medication in your blood drops too low, it will be unable to stop HIV reproducing.  This gives the virus an opportunity to develop resistance to the medication. The drug-resistant strains of the virus will become dominant.

If you become resistant to one medication, it is likely that you will become resistant to other medications in it’s class – this is called cross-resistance.  Although the risk varies from medication to medication, cross-resistance can occur in all classes of medication used to treat HIV.

If you have problems taking your medication you can talk to your HIV specialist, a Clinical Nurse Specialist or one of the NZAF therapeutic staff who may be able to assist.