Tenofovir: low resistance risk for new drug after six months therapy

Keith Alcorn
Estimated reading time 2 minutes
This article is more than 24 years old.

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.

Glossary

detectable viral load

When viral load is detectable, this indicates that HIV is replicating in the body. If the person is taking HIV treatment but their viral load is detectable, the treatment is not working properly. There may still be a risk of HIV transmission to sexual partners.

nucleotide

A building block of DNA or RNA, chemical structures that store genetic information. 

salvage therapy

Any treatment regimen used after a number of earlier regimens have failed. People with HIV who have experienced side-effects and/or developed resistance to many HIV drugs receive salvage therapy, sometimes consisting of a large number of medications.

placebo

A pill or liquid which looks and tastes exactly like a real drug, but contains no active substance.

nucleoside

A precursor to a building block of DNA or RNA. Nucleosides must be chemically changed into nucleotides before they can be used to make DNA or RNA. 

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.

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