Testing for resistance after starting treatment

Standard genotype assays generally are unable to detect mutations unless they are present in over 10-20% of the virus population, and provide optimum results while the virus remains under selective pressure of the resistant drug.

Transmitted drug resistance that impacts on viral fitness generally reverts to wild-type during the months and years after infection which will often limit the chance of detection with routine genotype tests. However, selective pressure from treatment that include resistant drugs, is likely to force resistant mutations to return to detectable levels within a few weeks of starting treatment.

Shealey and colleagues from Vanderbilt University Medical Center compared the results of pre-treatment testing compared to genotype tests after starting treatment in 24 chronically infected adults who had stored samples prior to starting treatment, and 3 months afterwards.

3/24 patient samples detected resistant mutations prior to treatment, with three additional patients showing resistance during initial drug pressure after a median 43 days (range 7-114).

The authors concluded that using resistance tests after starting treatment doubled the detection of resistance in chronically infected individuals form 12.5 to 25%, but that larger studies were required, and these studies could look at whether specific mutations are better detected post therapy than pre-therapy.

Comment

This is an interesting study and some clinicians may already use resistance testing 4 weeks after starting therapy in patients with suspected resistance that is unlikely to still be detected at baseline.

However this is probably only appropriate is a limited group and delaying resistance testing for all patients would subject those patients with detectable mutations to an unnecessary period of suboptimal treatment.

Current UK guidelines already recommend resistance testing after 4-12 weeks in patients with sub-optimal viral responses.

Shealey W, Shepard B, Sutton L et al. An alternative timing strategy for resistance genotyping. XV International HIV Drug Resistance Workshop, Sitges, Spain, July 2006. Abstract 166.