The mutation associated with reduced susceptibility to tenofovir (the K65R mutation) is more likely to emerge during treatment with abacavir, according to analysis of 999 tenofovir-naive patients attending the Chelsea and Westminster Hospital in London. The findings were presented at the Eighth Annual Conference of the British HIV Association at York University on April 19.
1757 genotypes from 999 patients were analysed for correlates for the presence of the K65R mutation. Seventeen cases were found; nine patients (6.2% of 186 abacavir-exposed individuals; confidence intervals 3% - 11.5%) had received treatment wth abacavir, while 8 patients had not (1% of abacavir-naive individuals; CI 0.4%-2%). Abacavir exposure was found to be the only factor associated with presence of the K65R mutation. No difference in the duration of nucleoside analogue treatment or the number of thymidine analogue (AZT and d4T-associated) mutations was found.
Thymidine analogue mutations were more common in those on abacavir with a high incidence of current thymidine analogue use whereas the K65R mutation was more common in those on abacavir with a lower incidence of thymidine analogue use. This suggests that two different pathways to tenofovir resistance exist, with the K65R mutation more likely to emerge in individuals without a high level of thymidine analogue mutations. Mutations at codons 41L or L210W are associated with a reduced response to tenofovir (Click here to read the report on this research study, presented at the Ninth Conference on Retroviruses and Opportunistic Infections in February.
Winston A et al. The prevalence and determinants of the K65R mutation in HIV reverse transcriptase in tenofovir-naive patients. Eighth Annual Conference of the British HIV Association, York, abstract 012, 2002.