AIDS TREATMENT UPDATE, Issue 38, February 1996
Keith Alcorn

The international study reviewed the records of 710 health care workers in France, the USA and the UK who reported accidental exposure to HIV-infected blood through, for instance, needlestick injuries between 1988 and 1994. Two hundred and fifty-six took AZT after the accident, and they had a reduced risk of HIV seroconversion compared with people who received no treatment. Researchers found that receiving a large quantity of blood, receiving blood from a patient at an advanced stage of AIDS, and not receiving AZT treatment after the accident were each factors significantly associated with subsequent seroconversion.

This is the first study to have looked at a large number of people who have suffered needlestick injuries and to have concluded that AZT may be beneficial. Past studies have included people with other forms of accidental exposure to HIV, or been too small to show a convincing effect. In this study, individuals who did not receive AZT were 79% more likely to seroconvert than those who underwent three to four weeks of AZT treatment immediately after an injury.

AZT seemed to reduce the risk of seroconversion even among those health care workers who were accidentally exposed to blood from an HIV-positive person who was himself taking AZT, and may thus have developed AZT-resistant HIV. However, the numbers involved in this comparison are so small that no conclusion should be based on it.

Although the results are statistically significant, they have not been accepted without question. This was not a randomised study, in which people who suffered needlestick injuries would be randomly allocated either to receive AZT or a placebo. In this retrospective study there could be other differences between the two groups which may explain the association between AZT use and a reduced risk of seroconversion, rather than it being a genuine effect of the drug.

GUIDELINES

Most hospitals have guidelines for staff about AZT post-exposure prophylaxis. These stress the importance of avoiding needlestick injuries in the first instance through good working practices, such as not attempting to replace sheaths on needles after use. Before starting work, staff are often encouraged to weigh up the pros and cons of taking AZT should they have an accident, and to make up their minds in advance, so that they can act promptly if an injury does occur.

ALTERNATIVES

Even if AZT does have genuine benefits as post-exposure prophylaxis, those benefits are partial - infections did occur despite AZT treatment.

One possible explanation relates to the fact that AZT is not active against HIV until it has been taken up by human cells and converted into a slightly different form (phosphorylated). This means there is time lag between the point at which someone starts to take AZT and the point at which the drug begins to inhibit HIV in the body. Some researchers have suggested that this lag may be as long as 48 hours. Anti-HIV drugs which do not require phosphorylation to become active, such as the protease inhibitors, may theoretically be better options for post-exposure prophylaxis.

Recent research with macaque monkeys has studied another potential alternative to AZT. Researchers injected 25 macaques with simian immunodeficiency virus (SIV) then the following day treated them with the drug PMPA. All the PMPA-treated monkeys were protected against full-scale SIV infection, while untreated control monkeys did become infected.

This is a much better success rate than AZT treatment has shown, and trials of PMPA as a post-exposure treatment, as well as an anti-viral drug for people with established HIV infection, are now planned.

REFERENCE

"Case-control study of HIV seroconversion in health-care workers after percutaneous exposure to HIV-infected blood - France, United Kingdom, and United States, January 1988 - August 1994". Morbidity & Mortality Weekly Report Vol. 44 No. 50, 22 December 1995.

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