IAS: AZT-related anaemia is rare, but may be less prevalent with fixed-dose combinations, meta-analysis shows

An analysis of 54 clinical trials including over 12,000 patients has concluded that severe anaemia is a rare side-effect of AZT (zidovudine) treatment, but that the risk is enhanced by a high viral load or low haemoglobin level before starting therapy. These findings were presented today at the Third International AIDS Society Conference on HIV Pathogenesis and Treatment in Rio de Janeiro.

The meta-analysis also suggested that patients taking AZT as Retrovir were more likely to become anaemic than those taking it as part of the ‘fixed dose combination’ tablets Combivir or Trizivir. Combivir also contains 3TC (lamivudine), while Trizivir is a combination of 3TC and abacavir in addition to AZT.

Anaemia is caused by having a low number of red blood cells, and is a well-known side-effect of AZT treatment. In order to compare the incidence of anaemia between patients taking and not taking AZT and to identify risk factors, investigators from the drug’s manufacturer, GlaxoSmithKline, gathered data from the 54 clinical trials involving AZT that were sponsored by the company between 1995 and 2004. These trials included AZT combined with various other anti-HIV drug regimens.

All of the trials lasted more than 24 weeks, and included a total of 12640 patients: 5565 took AZT and 7075 controls did not take the drug. All of the studies used AZT at the currently recommended dose of 250 or 300mg twice daily.

The researchers found that patients who were naïve to antiretroviral therapy had slightly higher rates of grades 2 to 4 anaemia if they took AZT (1.5 vs. 1.1%). However, in treatment-experienced patients, there was a wider gap between the patients who took AZT and those who did not (1.8 vs. 0.6%).

Using a ‘multivariate analysis’ to assess the impact of a range of factors on the risk of anaemia, the investigators calculated that taking AZT increased the risk 2.27-fold.

In addition, each 1 log₁₀ increase in viral load at the start of therapy increased the risk of anaemia by 36%, while a higher level of haemoglobin reduced the risk. Haemoglobin is the red oxygen-carrying molecule found in red blood cells.

However, the investigators did not examine the effect of other drugs included in the patients' regimens in their analysis of risk factors for anaemia.

Anaemia was more common among the patients taking Retrovir than those taking either Combivir or Trizivir (2.0 vs. 1.2%). “Reasons for this finding are not known but may include variability in the baseline characteristics that were identified as risk factors for the development of anaemia,” explain the investigators.