DEBATING AZT
AZT: A Medicine from Heaven

By Desmond Martin

The Citizen 31 March 1999

The Southern African HIV/AIDS Clinicians Society responds to an article AZT: A Medicine from Hell, by Anthony Brink, published in The Citizen on March 17.

Human Immunodeficiency Virus (HIV) disease is a major global health problem and is associated with a significant morbidity and mortality.

The number of people infected with HIV is rapidly increasing; recent estimates indicate more than 30 million adults and 1,1 million children are infected worldwide.  In South Africa it is estimated that in excess of three million people are infected.  It has been predicted that 40 million persons, including four to five million children, will have acquired the infection by the year 2000.  Mother-to-child transmission, the major cause of HIV infection in infants, has led to a 30 percent increase in the mortality rate of infants and children in recent years.

The introduction of highly active anti-retroviral therapy (HAART) has been good news.  In the US the age-adjusted death rate among people with HIV in 1997 was less than 40 percent of what it was in 1995.  This experienced was mirrored in other Western nations where dramatic declines in morbidity and mortality as a result of the increasing use of combination anti-retroviral therapy has occurred; many of these regimens contain AZT.

When AZT and other nucleoside analogues were first introduced they were used as monotherapy (a single drug was used).  Clinical experience quickly showed that the effect of a single drug was short-lived, as resistance to the drug developed.  It was then shown that by using a combination of drugs, a more lasting effect was obtained.

Beneficial

An added advantage of combination therapy was that the drugs acted at different stages of the replication cycle of the virus.  This option therefore made sense; the risk of drug resistance was drastically reduced and long-lasting beneficial effects have been recorded.  AZT together with 3TC and a protease inhibitor is a combination that has been found to be highly effective.

Impaired quality of life associated with the progression of HIV disease has a profound effect on the patient and leads to an increase in the direct medical and non-medical costs of illness. Published studies have shown that patients on combination therapy with AZT and 3TC have been able to maintain or more importantly improve their quality of life.

So effective are combination anti-retroviral regimens in reducing the complications of the disease that there are anecdotal reports emanating from the US that AIDS wards are being emptied of their patients and in some instances wards have been closed.  Clinicians are now treating patients in out-patient settings and the status of the disease has changed to that of a chronic manageable disease.

It is however, in the arena of prevention of HIV infection that AZT has produced dramatic results.

Worldwide, approximately 500 000 infants become infected each year as a result of mother-to-child transmission.  In some African countries 25 percent of pregnant women are infected with HIV.  Without preventative therapy up to a third of their babies may become infected; many of these children will die in their early years.

In 1994 a clinical trial conducted in the US and France (ACTG 076) demonstrated that AZT given to mothers during their pregnancies, intravenously during labour and orally to their babies for six weeks reduced the risk of mother-to-child transmission by 67 percent.  This regimen has been adopted as the "standard of care" in the US.

However, it is unsuitable for developing countries because of its complexity and cost.

To address the problem the Ministry of Health in Thailand introduced a trial of simpler and less expensive regimens of AZT to prevent mother-to-child transmission.  This trial showed that a simpler regimen of AZT given orally to mothers in the last weeks of pregnancy reduced the risk of transmission by 50 percent.  This short course AZT regimen (so-called Thailand regimen) is much more suitable for developing countries than the US-protocol because it is much easier to administer and less costly ($50 v $800).

Preliminary data from United Nation AIDS Programme (UNAIDS)- sponsored studies have also demonstrated that even more abbreviated, affordable, AZT-containing regimens may be equally effective. 

Another instance where preventative AZT therapy is commonly used is in the event of a health-care worker (HCW) sustaining an occupational exposure to blood or body fluids from an HIV infected person (eg. needle-stick injury).

These occurrences are usually charged with much emotion and HCW’s are, quite justifiably, entitled to appropriate post-exposure prophylaxis to be commenced as soon as possible after the injury.  A multinational study conducted among occupationally exposed HCW’s demonstrated a 79 percent reduction in the risk of acquiring HIV infection when AZT was used as post-exposure prophylaxis.

Toxicity

The toxicity of AZT is a very real issue however, the toxicity (particularly bone marrow toxicity) is usually noted in patients with advanced HIV disease whose bone marrow function may already be impaired by HIV disease.  Toxicity does not appear to be a problem during short-term use (post exposure prophylaxis or mother-to-child transmission prevention).

Nevertheless vigilance and monitoring on the part of the clinician is necessary.  If toxicity occurs the drug should be stopped and other drugs substituted and any appropriate management should occur.  Toxicity in most cases is reversible. In addition, careful monitoring of babies whose mothers took AZT during pregnancy has failed to show any significant abnormal findings.

Thus AZT in combination with other drugs has proved to be invaluable for the treatment of those already infected with HIV and has also proved to be a potent preventative agent in the mother-to-child setting and for occupational exposures.  For these very reasons the drug AZT deserves the accolade: AZT: a medicine from heaven.

Desmond J Martin is president of the Southern African HIV/AIDS Clinicians Society.

Note: Dr Martin has no conflict of interest and has not received financial sponsorship from GlaxoWellcome.