Tenofovir: resistance profile of non-responders becomes clearer

The new antiretroviral drug tenofovir (Viread) launched last month in Europe, is currently licensed for all patients who have experienced failure of at least one treatment regimen. Determining which patients will benefit from tenofovir has been somewhat hindered by a lack of information about precisely which reverse transcriptase mutations are associated with a poor response.

At last week’s Ninth Annual Retroviruses Conference, Gilead scientists presented further analysis from study 907, a 48 weeks study in which tenofovir was added to a failing treatment regimen, and study 902, a dose ranging study of tenofovir.

Patients in the 907 study had an average of 5.4 years of prior antiretroviral treatment, and of the 274 patients assigned to the genotypic resistance sub-study, 24% in the placebo group and 16% in the tenofovir group had nucleoside analogue-associated mutations at baseline.

As has been reported previously, a high degree of nucleoside analogue mutations blunted response to tenofovir in this study, but it was not clear which mutations were most strongly associated with reduced sensitivity to tenofovir.

This study found that mutations at codons 67, 70, 215 or 219 did not compromise response to tenofovir. Only those at codons 41L or L210W were associated with a reduced response.

The M41L mutation is relatively uncommon in people with extensive nucleoside analogue experience because it is a mutation that tends to arise early after the failure of AZT, and it fades once the T215Y mutation is selected. T215Y is not associated with tenofovir resistance.

Phenotypic susceptibility data were also presented to help in the definition of likely non-responders , since genotypic tests may not always pick up every mutation. A reduction in susceptibility of 3.8-fold or more was associated with non-response in this study.