Scientists from Gilead, devlopers of tenofovir, have reported that their new nucleotide anlaogue compound does not appear to provoke new resistance mutations in people who add the drug to a failing regimen. At the highest dose studied (300mg once daily) tenofovir reduced viral load by 0.75 log.
Tenofovir was studied in 189 individuals with detectable viral load (average 5,000 copies) at baseline. Patients were randomised to add one of three doses or a placebo to their existing therapy, and after 24 weeks genotypic resistance tests were carried out to see if tenofovir resistance had developed in patients with detectable viral load. It was not possible to test for genotypic mutations in the 23 individuals who achieved viral load below 50 copies after adding tenofovir, because resistance tests typically need viral load of 1,000 copies or above in order to reliably detect mutations.
The researchers found that only two of the patients with detectable viral load had developed a K65R mutation, which has been previously defined as associated with nucleotide analogue use. In both cases they were also taking ddI and abacavir, drugs also associated with this mutation. No other mutations that could be attributed to tenofovir were detected. Other mutations related to nucleoside analogues such as AZT and to protease inhibitors did continue to develop in individuals with detectable viral load.
These findings suggest that it may be possible to use tenofovir as salvage therapy to limit viral rebound without necessarily compromising its future combination with new drugs. Tenofovir is likely to enter clinical trials in the UK towards the end of 2000.
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Reference
Miller M et al. HIV-1 RT mutations in patients after 24 weeks of tenofovir disproxil fumarate (formerly PMPA prodrug) therapy added to stable background ART. Abstract 740a, Seventh Conference on Retroviruses, san Francisco 2000.