Alovudine is a nucleoside reverse transcriptase inhibitor (NRTI) that resembles AZT (zidovudine, Retrovir). An oral formulation of the drug has been developed, but the history of its development is rather complex.

Alovudine was first developed by the pharmaceutical company Lederle in 1992, but due to the absence of clear benefit over AZT, the company did not pursue further development. However, when information became available on resistance to AZT, researchers at Medivir tested alovudine activity against HIV variants highly resistant to AZT, and found that the compound was active against such viruses. Alovudine’s pharmacological profile makes it a candidate for once-daily dosing.

Medivir purchased the full rights to develop alovudine, completed phase I studies and reported phase II results in 2002. The drug has been developed under the codename MIV 310.

A study in 15 individuals with thymidine analogue resistance and detectable viral load with a median of six NRTI-associated mutations showed that adding alovudine 7.5mg once daily was effective in reducing viral loads. After four weeks, the greatest viral load reduction (1.88 log₁₀) was seen in the eleven individuals who did not receive d4T (stavudine, Zerit), while a smaller reduction was seen in patients who did receive d4T (0.54 log₁₀). There was no significant difference in response according to the number of thymidine analogue mutations^[1].

Alovudine’s earlier development was negatively affected by its side-effect profile, including anaemia and neutropenia, when used at a dose of 20mg a day. However, no serious side-effects were seen in the phase II study^[2].