A pan-European group of virologists, clinicians and treatment advocates published European guidelines on resistance testing in the journal AIDS last week. Led by Dr Veronica Miller of the Centre for Internal Medicine at JW Goethe University in Frankfurt, members from the UK and Ireland included Prof. Clive Loveday, Prof. Andrew Phillips and Dr Mike Youle of the Royal Free Hospital School of Medicine, Dr Deenan Pillay of Birmingham University Medical School and the PHLS Antiviral Susceptibility Reference Unit, and Dr Fiona Mulcahy of St James's Hospital, Dublin.
Summary of recommendations for testing
Treatment naïve patients
Resistance testing should always be considered in treatment naïve patients before starting therapy. It is also advisable to store plasma samples as soon as possible after the identification of infection, since resistant mutants acquired during infection may decline below detectable levels in the absence of selective drug pressure.
In primary infection or recent infection, test for resistance if the local transmission rate of drug -resistant virus is high, or there are grounds to suspect transmission of drug-resistant virus.
In cases of post-exposure prophylaxis, treatment should not be delayed while the result of resistance testing of the index case is awaited, but should be adjusted later if resistance is detected. The test results should be made available before PEP is normally terminated i.e. within 28 days.
Changing treatment
Resistance testing is recommended for all patients experiencing treatment failure if a change of treatment is being considered.
The guidelines do not recommend specific genotypic or phenotypic assays, but do recommend that all resistance test results should be supplied to clinicians with the following information:
- A list of genotypic and/or phenotypic changes detected and their relevance for particular drugs
- Adequate expert interpretation of the changes to allow a new regimen to be chosen
In pregnancy
Expectant mothers with detectable viral load on treatment should be screened for resistance and treatment should be adjusted before delivery (taking into account the need to avoid exposure to certain drugs during pregnancy or during the first trimester).
Treatment naïve expectant mothers should be screened for resistance if they present before delivery, and maternal treatment and infant prophylaxis should be tailored according to drug susceptibility.
Mothers presenting at a very late stage should receive resistance screening if at all possible, but this should not delay the initiation of therapy. Treatment can be adjusted according to the results of a resistance test, if necessary.
In all cases, viral load should be monitored frequently [editor's note: interval not currently defined] and any suboptimal response should lead to further investigation of adherence and other factors.
In children
Children born to mothers with detectable viral load should receive resistance testing. Responses to treatment chosen on the basis of resistance testing are currently being evaluated in the PENTA 8 study.
Recommendations of the EuroGuidelines group for future development
- A European surveillance system should be set up to monitor differences in transmission of drug-resistant virus between regions and risk groups.
- Resistance testing guidelines and educational material need to be disseminated in an integrated manner across Europe in order to ensure an integrated standard of care.
Reference
The EuroGuidelines Group for HIV resistance. Clinical and laboratory guidelines for the use of HIV-1 drug resistance testing as part of treatment management: recommendations for the European setting. AIDS 15: 309-320, 2001.