Transmission of drug resistance – at 11% in Europe and 17% in the UK

Confirmation of the increase in transmission of drug resistance was presented in several studies, and in pooled results in one large European study. The CATCH study (Combined Analysis of resistance Transmission over time of Chronically and acute HIV-infected patients in Europe) whose title doesn’t exactly trip off the tongue provided evidence of an alarmingly high rate of transmission of drug resistance in Europe.

Wensing and colleagues presented results from an analysis of more than 1,400 baseline genotypic samples collected between 1996 and 2002 in 16 countries.

Reverse transcriptase (RT) and protease (PI) sequences were received from the following countries: Austria (60), Belgium (61), Denmark (132), Finland (8), Germany (62), Greece (40), Israel (104), Italy (296), Luxembourg (163), the Netherlands (25), Norway (23), Poland (35), Portugal (124), Serbia-Montenegro (10), Spain (23) and Switzerland (262). Mutations conferring resistance to nucleosides were seen in 6.9% of isolates, resistance to NNRTIs in 2.6% of cases and to PIs in 2.2%. Multi-drug resistant virus was observed in 1.7% of subjects.

Population characteristics were available for 975 samples, and primary drug mutations associated with protease inhibitors and reverse transcriptase were detected in 11% and 9% respectively from these treatment naïve individuals. Primary mutations were detected in 11% (63/596) of seroconverters (infected <1 year) and 8% (30/379) of those with chronic infection. Thirty-one percent of the sequences were classified as non-B and in all countries except Israel, resistance was higher in subtype B sequences than non-B (12% versus 5%).

The UK appears to have higher levels than shown in this European study: the British picture was detailed in an abstract by Deenan Pillay on behalf of the UK HIV Drug Resistance Database – a collaboration between virology laboratories and major clinical centres to pool resistance data in the UK.

Firstly reporting on treatment experienced patients, just over 9,800 test results from around 7,000 patients were available from 1996 to March 2003, and the results were divided into three time periods: 1996-1998, 1999-2000 and 2001-2003. As resistance testing in widely used in early treatment failure, it is not unexpected that around 70% of samples in each period from treatment experienced patients showed at least one key RTI mutation. PI resistance in this group was detected in 26, 32 and 27% of the samples in each period and NNRTI resistance is still increasing in prevalence at 20, 40 and 48% of experienced patients over time – reflecting the prescribing practice for NNRTI first-line therapy in the UK.

Key resistance mutations in treatment naïve individuals (to compare to the CATCH study) were detected in 10, 16 and 17% of samples for the 1998-1999, 1999-2001 and 2001-2003 periods respectively.

Comment

These data support the decision in the BHIVA Treatment Guidelines to now recommend baseline resistance testing in the UK for all newly diagnosed individuals, even when immediate treatment is not being considered.

UK guidelines also now recommend resistance testing for chronically infected patients prior to initiation of therapy due to this increasing prevalence and the low cost.

With the high rate of transmitted drug resistance now in circulation this would seem entirely prudent. For those citing cost as an obstacle, deferral of commencement of treatment for just one month will cover the cost of assay.