17th International HIV Drug Resistance Workshop 10-14 June 2008, Sitges, Spain

GENOTYPIC ANALYSIS OF PATIENTS ENROLLED IN STUDY AVX-201 AND TREATED WITH APRICITABINE FOR 24 WEEKS

Antivir Ther. 2008; 13(Suppl. 3):A22 (abstract no. 20)

S Cox, J Southby and S Moore
Avexa Ltd, Melbourne, Victoria, Australia

BACKGROUND: Apricitabine is a novel cytidine analogue nucleoside reverse transcriptase inhibitor (NRTI). Apricitabine retains activity in the presence of the M184V mutation in HIV-1 reverse transcriptase (RT) alone or when accompanied by thymidine analogue mutations (TAMs – by either pathway) or other nucleoside analogue mutations (NAMs), such as L74V. AVX-201 is a 48-week study of apricitabine compared with lamivudine in patients failing therapy with M184V, with or without additional mutations. Genotypic analysis of patient isolates was performed at baseline, after 21 days of functional monotherapy with apricitabine and after 24 weeks of treatment with apricitabine together with an optimized background to search for any development of resistance to apricitabine.

METHODS: The approved Bayer Trugene® HIV-1 genotyping assay was used to sequence HIV-1 RT from plasma samples of patients enrolled in the AVX-201 study at screening, baseline, day 21 (after 21 days on functional monotherapy with apricitabine), week 12 and week 24. Background therapy was optimized on day 21 according to the screening genotype.

RESULTS: At baseline, the distribution of genotypes (n=50 in total, all M184V) was M184V alone, n=17; M184V plus the following: 74V, n=7; 1 TAM, n=3; 2 TAMs, n=3; 3 TAMs, n=14; 4 TAMs, n=6; 5 TAMs, n=4; 6 TAMs, n=1; and 41L/210W, n=13. No patients had K65R present at baseline. Evidence of non-NRTI resistance was common. At day 21, 38/38 genotypes obtained had M184V. At week 12, 10/14 had M184V, 2/14 had M184M/V and two had reverted to 184M. At week 24, 6/9 had M184V and three had reverted to 184M. Very few other changes were seen and no patients developed K65R. Individual genotypes will be presented.

CONCLUSIONS: No additional mutations developed in patients treated with apricitabine either during a 21-day period of functional monotherapy, nor up to 24 weeks in combination with an optimized background. The M184V mutation was maintained in the majority of patients where a genotype could be obtained. No development of K65R, L74V, TAMs or other NAMs was seen.

2008-06-10
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