Usage of Antivirals and the Occurrence of Antiviral Resistance in Norway 2017
Report
|Published
The annual report from Resistance against Antivirals in Norway (RAVN) presents national surveillance data on antiviral resistance for a number of viruses.
Key message
The usage of antivirals
The sales of antiviral drugs continued to increase measured in defined daily doses (DDDs), according to The Norwegian Drug Wholesales statistics database. The cost of antiinfectives for systemic use (ATC group J) has also increased during recent years although the yearly increase has been smaller since 2016. Introduction of new antivirals for treatment of HCV infections has highly influenced the increased costs in this group, but price reduction for some of these drugs has resulted in a relatively lower increase in cost compared to the increase in sales. For HIV drugs the sales measured in number of DDDs have been relatively stable in recent years, but there has been a significant change in the pattern of use with a transition from single ingredient products to fixed combinations.
Influenza virus
No mutations conferring resistance against oseltamivir and zanamivir were detected in the 2017/18 season. Resistance mutations found at the end of the 2015/16 season were apparently not transferred to the few H1N1-viruses circulating this season. All circulating influenza strains are currently resistant to adamantanes. The reference laboratory therefore do not routinely analyse for adamantan resistance. In Norway, only oseltamivir is now available for antiviral treatment of influenza.
HIV-1
Surveillance drug-resistance mutations (SDRMs) were detected in 5.6% of samples from patients with newly diagnosed HIV-1 infection in Norway in 2017. The prevalence of transmitted drug resistance has been stable for the past few years with only minor variation. The introduction of prophylactic treatment (PrEP and PEP) could challenge this situation. RAVN is currently conducting a study which aims to connect epidemiological data from MSIS with resistance data. Preliminary results from this study show that only 30% of the reported cases in 2016 were infected in Norway. In this group, 7.5% of the samples had SDRMs.
Hepatitis B virus
In 2017, 23 patient samples were submitted for HBV antiviral resistance testing. Among these, only two cases of resistance were detected. Among samples submitted primarily for HBV genotyping (N=223), no drug resistance mutations were detected.
The burden of resistance against HBV antivirals seems to be low in Norway given the large number of patients on treatment. However, the data is very limited due to the low frequency of testing and should therefore be interpreted carefully.
Human herpes viruses
In 2017 the reference laboratory received specimens from 27 patients for genotypic analysis of CMV resistance and mutations in the CMV-UL97 gene, conferring resistance to ganciclovir, were recorded in 7 cases (26%). In one patient additional mutations in the Usage of Antivirals and the Occurence of Antivarals Resistance in Norway • Folkehelseinstituttet 9
CMV-UL54 gene conferring foscarnet- and cidofovir resistance were seen. Most cases of treatment failure are thus not due to the development of resistance to anti-CMV-therapy. Aciclovir and its prodrug valacicklovir are extensively used for both treatment and prophylaxis of herpes simplex virus-1 and -2 (HSV) infections. Despite the high consumption of these antiviral drugs treatment failure due to drug resistance is quite uncommon. In 2017 ten specimens were sent from Norway to Folkhälsomyndigheten, Sweden for genotypic resistance testing. Mutations conferring resistance to aciclovir/valaciclovir were seen in two of these specimens.
Hepatitis C virus
In most cases, Hepatitis C can be cured by a 12-week oral regimen with a combination of two direct-acting antiviral drugs (DAAs). Hepatitis C treatment has few side effects and everyone who is infected should be identified and offered treatment. Treatment failure after combination therapy with DAAs is rare and will only occur in approximately 3% of those treated. Predictors of treatment failure include genotype 3 infection, the presence of resistance associated variants (RAVs) and advanced liver fibrosis. With such good response rates to the first-line treatments, there is seldom need for resistance testing before hepatitis C treatment is administered.
Summary
The usage of antivirals
The sales of antiviral drugs continued to increase measured in defined daily doses (DDDs), according to The Norwegian Drug Wholesales statistics database. The cost of antiinfectives for systemic use (ATC group J) has also increased during recent years although the yearly increase has been smaller since 2016. Introduction of new antivirals for treatment of HCV infections has highly influenced the increased costs in this group, but price reduction for some of these drugs has resulted in a relatively lower increase in cost compared to the increase in sales. For HIV drugs the sales measured in number of DDDs have been relatively stable in recent years, but there has been a significant change in the pattern of use with a transition from single ingredient products to fixed combinations.
Influenza virus
No mutations conferring resistance against oseltamivir and zanamivir were detected in the 2017/18 season. Resistance mutations found at the end of the 2015/16 season were apparently not transferred to the few H1N1-viruses circulating this season. All circulating influenza strains are currently resistant to adamantanes. The reference laboratory therefore do not routinely analyse for adamantan resistance. In Norway, only oseltamivir is now available for antiviral treatment of influenza.
HIV-1
Surveillance drug-resistance mutations (SDRMs) were detected in 5.6% of samples from
patients with newly diagnosed HIV-1 infection in Norway in 2017. The prevalence of
transmitted drug resistance has been stable for the past few years with only minor
variation. The introduction of prophylactic treatment (PrEP and PEP) could challenge this
situation.
RAVN is currently conducting a study which aims to connect epidemiological data from MSIS
with resistance data. Preliminary results from this study show that only 30% of the reported
cases in 2016 were infected in Norway. In this group, 7.5% of the samples had SDRMs.
Hepatitis B virus
In 2017, 23 patient samples were submitted for HBV antiviral resistance testing. Among
these, only two cases of resistance were detected. Among samples submitted primarily for
HBV-genotyping (N=223), no drug resistance mutations were detected.
The burden of resistance against HBV antivirals seems to be low in Norway given the large
number of patients on treatment. However, the data is very limited due to the low
frequency of testing and should therefore be interpreted carefully.
Human herpes viruses
In 2017 the reference laboratory received specimens from 27 patients for genotypic
analysis of CMV resistance and mutations in the CMV-UL97 gene, conferring resistance to
ganciclovir, were recorded in 7 cases (26%). In one patient additional mutations in the
Usage of Antivirals and the Occurence of Antivarals Resistance in Norway • Folkehelseinstituttet
9
CMV-UL54 gene conferring foscarnet- and cidofovir resistance were seen. Most cases of
treatment failure are thus not due to the development of resistance to anti-CMV-therapy.
Aciclovir and its prodrug valacicklovir are extensively used for both treatment and
prophylaxis of herpes simplex virus-1 and -2 (HSV) infections. Despite the high
consumption of these antiviral drugs treatment failure due to drug resistance is quite
uncommon. In 2017 ten specimens were sent from Norway to Folkhälsomyndigheten,
Sweden for genotypic resistance testing. Mutations conferring resistance to
aciclovir/valaciclovir were seen in two of these specimens.
Hepatitis C virus
In most cases, Hepatitis C can be cured by a 12-week oral regimen with a combination of
two direct-acting antiviral drugs (DAAs). Hepatitis C treatment has few side effects and
everyone who is infected should be identified and offered treatment. Treatment failure
after combination therapy with DAAs is rare and will only occur in approximately 3% of
those treated. Predictors of treatment failure include genotype 3 infection, the presence of
resistance associated variants (RAVs) and advanced liver fibrosis. With such good
response rates to the first-line treatments, there is seldom need for resistance testing
before hepatitis C treatment is administered.
