AZT and d4T Cross-resistance
STEP has reported data in past articles suggesting that a history of either Retrovir® (AZT) or Zerit® (d4T) might create cross-resistance to the other drug. This is due to the specific mutations that can cause resistance to both of these drugs. A study looking at evidence of cross-resistance between the two drugs was presented by Hernandez and colleagues at the Durban conference. In their study, blood samples from 85 people who had received Zerit®, but not Retrovir®, were analyzed. The researchers concluded that 28% of the people studied had mutations that could cause resistance to either or both of the drugs.
A second study conducted by Nicastri and colleagues examined 56 people who had taken either Zerit® and Epivir® (3TC), or Retrovir® and Epivir®, to see what type of mutations had developed. Mutations that could cause resistance for Retrovir® were found in 44% of the people studied who had taken Retrovir® and Epivir® for 18 months. Resistance for Retrovir® was found in 40% of the people who had taken Zerit® and Epivir® for 18 months. This information further supports that use of both Zerit® and Retrovir® can create mutations that cause cross-resistance. This resistance data must be viewed with some degree of caution, however, because clinically, people who have failed Retrovir® seem to respond well to Zerit®, and conversely, people who have failed Zerit® seem to respond well to Retrovir®. Studies in the next year will provide insight into the pathways of common resistance to both of the thymidine analog drugs, Zerit® and Retrovir®.