Usage of Antivirals and the Occurrence of Antiviral Resistance in Norway 2021
The annual report from Resistance against Antivirals in Norway (RAVN) presents Norwegian data about antiviral resistance and covers topics related to the treatment of viral infections. The report presents data from the resistance surveillance of viruses for 2021 and provides an overview of the use of antiviral agents in Norway. In addition to the surveillance data, the report contains thematic chapters dealing with the importance of antiviral resistance and resistance studies in the clinical management of patients with HIV, HBV, HCV, CMV and genital herpes infections. These chapters are written by experienced clinicians with a particular interest in these viral infections. They have also supplemented the chapters with interesting case studies from clinical practice that illustrate some of the practical challenges when dealing with antiviral resistance.
The usage of antivirals
According to The Norwegian Drug Wholesales Statistics Database, the sales of antiviral drugs measured in defined daily doses (DDDs) were reduced in 2021, after several years of increase. This reduction was primarily due to a small decrease in sales of antivirals against HIV, which make up a large proportion of the antiviral drugs sold in Norway. There was no decrease in the number of people being treated with HIV drugs compared to previous years, but as a growing proportion of patients is treated with single tablet regimens, the number of drugs sold is reduced.
When looking at the number of persons treated with antiviral drugs, the antiviral treatment received by the highest number of patients are drugs used against herpes viruses. In 2021, the sale of antivirals against herpes virus, especially valaciclovir, increased even further. There was a decrease in the sales of agents against hepatitis C and influenza, while treatments for hepatitis B were unchanged.
Similar to the previous influenza season, the season of 2021/2022 was also unusual, mainly due to the infection control measures implemented in response to the pandemic. There was a very low incidence of influenza at the beginning of the season, followed by a short period with significant spread of infection during the spring of 2021. No drug resistance against neuraminidase inhibitors was detected, but a mutation conferring resistance to the new drug baloxavir marboxil was found in one sample.
Human immunodeficiency virus-1
The decreasing trend in the number of new HIV-infections has continued in 2021, which is also reflected in a reduction in the number of samples received for surveillance of primary drug resistance. A total of 64 samples were analysed as part of the surveillance in 2021, and only 13 of these were from patients infected in Norway.
For the first time, we have been able to classify cases according to site of residence at the time of infection. Among those living in Norway at the time of infection, as much as 88% of the cases reported to MSIS were also reported to RAVN. This indicates that national routines for follow-up of newly diagnosed patients with regard to antiviral resistance are good. Resistance mutations were detected in 11% of the examined samples, which is comparable to previous years. In 2021, only mutations affecting reverse transcriptase inhibitors and none affecting protease inhibitors were found.
Hepatitis B virus
In 2021, a total of 134 samples with hepatitis B virus (HBV) were analysed for resistance mutations. Most of these samples (n=117) had been submitted to the reference laboratory for genotyping prior to treatment. These samples constitute the Norwegian surveillance of primary resistance. The remaining 17 samples were from patients with ongoing antiviral treatment, and were submitted for investigation of resistance as a possible cause of treatment failure. Relevant resistance mutations were found in five of the 17 samples from
patients with treatment failure. No resistance mutations were found in any of the surveillance samples.
Human herpes viruses: Cytomegalovirus
In 2021, 19 samples were submitted for resistance testing at the reference laboratory for cytomegalovirus (CMV). Relevant resistance mutations were detected in five of these samples. Low or moderate resistance to ganciclovir was found in four of these samples, while moderate resistance to the new drug maribavir was found in one sample. There is no systematic surveillance of resistance in CMV, and the true incidence of drug resistance cannot be determined.
Human herpes viruses: Herpes simplex virus
In 2021, only five samples with herpes simplex virus (HSV) were analysed for resistance. Two of the samples had mutations conferring resistance to aciclovir. Despite an increase in the use of aciclovir both as treatment and prophylaxis, samples are rarely submitted for resistance testing. Like CMV, there is no systematic surveillance of HSV drug resistance.
Hepatitis C virus
A systematic surveillance system for newly diagnosed HCV infections was launched in May 2022. In 2021, resistance testing was performed on a limited number of samples submitted for resistance testing. Drug resistance data is cross-referenced with epidemiological data from MSIS to enable comparisons of different subgroups. Resistance associated substitutions were detected in seven out of eight samples analysed for
resistance, two of which were from treatment experienced patients, one sample was from a patient with no previous treatment exposure and the remaining four were from patients where treatment exposure was not known.
Surveillance of antiviral resistance in SARS-CoV-2 has not been collected to RAVN in 2021. Oral drugs for the treatment of COVID-19 will be available in Norway from the autumn of 2022, and a system for surveillance of antiviral resistance will probably be implemented from the beginning of 2023. This surveillance will be based on the same sequence data that is part of the national monitoring of variants.