+VE DRUG WATCH
 
IN THE BEGINNING THERE WAS AZT

 This is the first of many articles looking at the different drugs currently available in the treatment of HIV. Tracy Barnes starts with the first ever licensed drug.

DRUG NAME:	Zidovudine (AZT)
DRUG CLASS:	Nucleoside reverse transcriptase inhibitors (NRTIs), nucleoside analogues or 'Nukes'.
BRAND NAME:	Retrovir®

ALSO INCLUDED IN:
Lamivudine (3TC or Epivir) to produce Combivir.
Lamivudine (3TC/Epivir and abacavir/Ziagen) to produce Trizivir.

HOW NRTIs WORK:
AZT (or azidothymidine) belongs to the family of drugs referred to as nucleoside reverse transcriptase inhibitors (NRTIs) or nucleoside analogues. This class of drugs combat viral replication by disrupting the essential transcription process of HIV genetic material (RNA) into DNA.

HISTORY:
AZT is often referred to by its generic name zidovudine. Its trade name is Retrovir and it was the first licensed drug for the treatment of HIV infection.

In the past when AZT was the only available treatment for HIV it was prescribed to be taken as a single drug treatment (monotherapy).

Today, apart from the use of AZT in pregnancy (to reduce the risk of transmission from mother to child), it is only used in combination with other drugs to suppress viral replication.

COMBINATION THERAPY:
For most people the corner stone of triple therapy consists of a combination of two nucleoside analogue reverse transcriptase inhibitors (NRTIs), such as AZT and ddI; d4T and 3TC etc.

AZT based combination therapy, has, until recently, been the most commonly prescribed therapy for those starting treatment for the first time. The most common alternative option is d4T.

Patients will be prescribed either AZT or d4T, they will never be put on both as they are incompatible.

AZT DOSING:
AZT is produced as both a 100mg and 250mg capsule. A daily dose of either 500mg or 600mg is usually prescribed and should be taken either twice a day or three times a day.

A twice daily dose of 250mg capsule is the most common prescribed regime with an additional 100mg capsule for dose differences. AZT should be stored at room temperature.

DOSING RESTRICTIONS:
There are no food restrictions or recommendations with AZT and the dose may be taken with or without food.

Some studies have shown an increased drug efficacy when you take AZT on an empty stomach (this may not be possible if other drugs in your combination have to be taken with food.

INCREASED LEVELS:
It has been illustrated that methadone and other opiate drugs double the level of AZT in the blood, resulting in necessity for only half the standard dose.

SIDE EFFECTS OF AZT:
As with most anti-retroviral treatments, side-effects more commonly occur when treatment is first commenced and often decrease or disappear after 4 or 5 weeks of treatment.

THE MOST COMMONLY REPORTED SIDE EFFECTS OF AZT INCLUDE:
nausea and vomiting, headache, fatigue, weakness, muscle pain.

OTHER LESS COMMON SIDE-EFFECTS MAY INCLUDE:
rash, severe muscle pain and inflammation, insomnia, nail discolouration, kidney disorders.

Because AZT may damage the bone marrow, patients may occasionally develop anaemia and/or low white blood cell counts, for this reason blood should be tested frequently, especially at the start of an AZT-based treatment regime. These blood anomalies are more likely to occur in individuals with advanced HIV infection or who are already prescribed medications associated with them.

COMBATING SIDE EFFECTS:
Very often side-effects can be combated with simple measures and/or over the counter treatments.

Taking AZT prior to eating and making small adjustments to diet often reduces nausea and vomiting. Eating little and often, avoiding fried, spicy and sweet foods, eating more cool foods and drinks may also help, as could increasing fluid intake.

While the above side-effects should cause little concern and are relatively easy to remedy it should be noted that some side effects should be taken more seriously. Severe abdominal pain, shortness of breath, excessive tiredness or weakness, unusual bleeding or bruising, sore throat, high temperature or delayed healing of any injury should be reported immediately to a physician as a matter of precaution.

PRE-EXISTING CONDITIONS:
If there is a pre-existing liver or kidney problem additional monitoring may be necessary to ensure the condition does not worsen, in these instances it may also determine dose reductions.

PROLONGED TREATMENT:
Treatment with AZT over a prolonged period of time presents a small chance of muscle damage, occurring, particularly relating to the hips, thighs and buttocks. Symptoms usually include some pain, muscle wasting and weakness.

RARE SIDE EFFECTS:
Much rarer side effects to AZT include enlarged fatty liver and increased levels of lactic acid in the blood, more likely to occur in those at risk of liver disease and obese females.

DOSING FOR DRUGS CONTAINING AZT:
AZT is contained in:

• Combivir - a 450mg tablet requiring twice daily dosing with or without food (300mg of AZT combined with 150mg of 3TC/lamivudine).
• Trizivir - a 750mg tablet requiring twice daily dosing with or without food (300mg AZT with 150mg 3TC/lamivudine and 300mg Ziagen/abacavir).

PAEDIATRIC USE OF AZT:
AZT is also used for the treatment of HIV in children from the age of 3 months.

Where appropriate 100mg and 250mg tablets or capsules will be prescribed.

Dosages for children are weight-based and divided into three or four doses per day, with a maximum dose allowance of 200mg every six hours.

AZT TREATMENT DURING PREGNANCY:
For some time AZT has been used during pregnancy and labour to reduce the incidence of mother-to-baby transmission. Studies have revealed that neither mother or child experience significant short-term side effects. Long term effects on mother and child are still under investigation.

AZT RESISTANT HIV:
Unfortunately cross resistance among NRTIs is common, significantly reducing future drug options within the NRTI class.

If AZT-resistant strain of HIV develops, it will persist for some time after AZT has been discontinued.

USING AZT AND 3TC TOGETHER:
It has been illustrated that by using AZT and 3TC in combination, AZT-resistant strains are less likely to develop.

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