Viruses monitored for resistance
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In Norwegian Surveillance System for Antiviral Resistance (RAVN), resistance of influenza viruses, HIV, hepatitis B virus (HBV), hepatitis C virus (HCV), cytomegalovirus (CMV) and herpes simplex virus (HSV) are monitored. Resistance in SARS-CoV-2 will be included in the 2022 surveillance.
The Norwegian Institute of Public Health has systematically monitored resistance to influenza viruses since 2005. Since 2006, samples from all newly diagnosed HIV cases have also been examined for primary resistance. Later, the surveillance was extended to all viral infections where specific antiviral treatment is available. The resistance determinations are performed at the microbiological reference laboratories, and resistance data are submitted to the Norwegian Institute of Public Health and stored anonymised in the RAVN registry.
Surveillance of resistance to HIV infection
The Norwegian Institute of Public Health collects resistance data from all people with newly diagnosed HIV infection in Norway. Most of these have never before been treated with HIV medication. The surveillance provides a useful estimate of the incidence of infection with resistant virus among those who are to start treatment in Norway. Although there is little transmission of resistant HIV in Norway, many are infected in other countries where the incidence is higher. Resistance that occurs during treatment is called acquired resistance and is more common than transmitted resistance (primary resistance). There is currently no systematic surveillance of acquired resistance in Norway.
Genotypic resistance determination of HIV is performed at the National Reference Laboratory for HIV at Oslo University Hospital, Ullevål. Resistance testing is performed by sequencing the regions of the genome that encode the viral proteins targeted by the antiviral agents: reverse transcriptase, protease and integrase. Sequencing looks for mutations that are associated with reduced sensitivity to the various drugs.
Resistance to integrase inhibitors is only studied in patients treated with this class of drugs. Therefore, only gene sequences encoding protease and reverse transcriptase are included in the surveillance.
Norway contributes to various European collaborations, and data from Norway are reported to ECDC's programme for resistance surveillance of HIV and to the European collaborative network SPREAD (Strategy to Control SPREAD of HIV Drug Resistance).
HIV resistance determinations are performed at the Department of Microbiology, Oslo University Hospital, Ullevål.
Influenza resistance
The Norwegian Reference Laboratory for Influenza Viruses at the Department of Virology (NIPH) is also the WHO National Influenza Centre (NIC) Norway. The reference laboratory monitors the occurrence of influenza virus in Norway.
A volunteer network of sentinel doctors submit respiratory tract samples from patients with influenza-like illness. In addition, all the microbiological laboratories in the country send in confirmed strains to the reference laboratory.
Resistance surveillance uses both genotypic analyses and phenotypic resistance testing of cultivable viruses. During the influenza season, weekly results from this resistance surveillance are published on the Norwegian Institute of Public Health's website.
Since 1999, a worldwide network for surveillance of resistance to neuraminidase inhibitors (NISN) has operated.
As part of the framework of European co-operation, resistance testing is performed on viruses which the national laboratories in the European Influenza Surveillance collaboration (EISN) send to the WHO's reference laboratory in England. Work is continuing into standardisation, advice, training and establishing analyses in the countries that want to do their own testing. Norway participates in this surveillance and has sent influenza virus isolates to the WHO Collaborating Centre in England for resistance testing, while also performing analysis here.
Hepatitis B and C infection
The Norwegian Institute of Public Health is a reference laboratory for viral hepatitis and has performed resistance studies of hepatitis B virus (HBV) since 2004 and of hepatitis C virus (HCV) since 2020.
The reference laboratory receives a small number of samples for the determination of HBV resistance from patients with treatment failure during antiviral treatment. In addition, a general surveillance of resistance is performed on a selected sample of samples from patients with chronic infection where genotyping is performed.
The method for resistance determination of HCV was established at the HCV reference laboratory at the Norwegian Institute of Public Health in 2020. The analysis is based on complete genome sequencing of HCV with Next Generation Sequencing, which looks for mutations associated with resistance to the various antiviral agents used against HCV.
Systematic surveillance of resistance mutations among newly diagnosed people in Norway was established in May 2022 according to a model from the Norwegian resistance surveillance of HIV.
Cytomegalovirus (CMV) infection and herpes simplex (HSV) resistance
The preferred treatment of CMV infections among immunosuppressed patients is currently ganciclovir. Usage is increasing as several conditions are currently treated with immunosuppressive or immunomodulatory drugs. In recent years when resistance to ganciclovir was discovered, there have been several new treatment alternatives in addition to foscarnet or cidofovir, which were the only alternatives.
Genotypic resistance determination of CMV is performed in Norway at Rikshospitalet, Oslo University Hospital, which is the national reference laboratory for CMV.
For resistance regulations, contact the Department of Microbiology, Oslo University Hospital.
HSV-1, HSV-2 and varicella zoster virus (VZV) can be treated with acyclovir. Resistance is a minor problem here. Samples for genotypic resistance determination are sent directly to Sahlgrenska University Hospital in Gothenburg, which is the national reference laboratory for the herpes virus in Sweden.
For resistance determination, contact the Clinical Microbiology Business at Sahlgrenska University Hospital.
