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This case report underscored the importance of performing accurate genotyping before initiation of therapy.
A 70-year-old male patient of Vietnamese descent requested treatment for hepatitis C virus (HCV) infection following the approval of the NS3/4A protease inhibitors. He had been treated 13 years earlier with interferon alfa monotherapy. Seven years ago, he was treated with pegylated interferon alfa-2b and ribavirin combination therapy. Both treatments were unsuccessful.
When his primary care doctor sent a blood sample for genotyping, the results indicated a mixture of HCV genotypes 1a and 6c. The physician decided to prescribe triple therapy of peginterferon alfa-2a (self-administered subcutaneously once weekly) and ribavirin (an oral regimen taken every morning and afternoon) for four weeks. At the fifth week, the patient was prescribed boceprevir to be taken orally every eight hours, along with the original dual therapy.
At first the patient’s serum HCV RNA viral load was 15,700,000 IU/mL (7.2 log). After four weeks of dual-therapy treatment, the viral load climbed to 22,700,000 IU/mL (7.36 log). At week 8, the viral load dropped to 462,882 IU/mL (5.67 log), but it increased at week 12 to 16,500,000 IU/mL (7.22 log). The physician decided to increase the ribavirin dosage, but by week 16, the viral load hit 21,000,000 IU/mL (7.32 log). The doctor stopped the triple therapy for HCV and referred the patient to an outpatient HCV clinic for care.
“A blood sample was sent to an alternative laboratory services company for confirmatory HCV genotype testing. The results indicated genotype 6 HCV rather than genotype 1a/6c disease (as previously determined), indication that the patient didn’t have a mixed-genotype HCV infection,” stated Linda M. Spooner, PharmD, BCPS, and colleagues who published this case report in the February issue of the American Journal of Health-System Pharmacists.
“We concluded that this patient was not a candidate for triple therapy in the first place but received it due to misgenotyping. We continue to follow this patient in the hope that he may be a candidate for future non-interferon-based therapies with directly acting agents,” the authors said.
The most common genotypes for HCV infection in the United States are genotype 1, followed by genotypes 2 and 3. HCV genotypes 4, 5, and 6 are not seen very often in the United States, said Spooner, who is associate professor of pharmacy practice, School of Pharmacy, MCPHS University, Worcester, Mass.
In patients from Asia and Asian immigrants to the United States, the most common HCV genotypes are 5 and 6. The genotype in the patient from Vietnam was 6.
“So when his physician tried to treat him as if he had a genotype 1 infection and the treatment failed, the case proved that the treatment for genotype 1 infection is not the same treatment that we do for genotype 6,” Spooner told Drug Topics.
This case report demonstrated that accurate genotyping must be made before initiation of therapy. It is also important to note that genotype assays are not always accurate, Spooner said.
“The older line probe assays cannot effectively differentiate between genotype 1 subtypes and genotype 6 subtypes. Therefore, in a patient of Southeast Asian descent, it may be preferable to conduct genotyping with the newer line probe assays,” the authors wrote. And if results indicate a mixed infection with HCV genotype 1 and 6 subtypes, providers should consider making another test to confirm this.
Spooner plans to start treatment soon for an Asian patient from China who has HCV genotype 6 infection, using the newly approved sofosbuvir (Solvaldi). Although the drug has been approved for patients with HCV genotypes 1-4, it is active against all the genotypes (1-6), so Spooner will use sofosbuvir off-label for HCV genotype 6 infection.
“Even though the drug is super-expensive [$1,000 per pill], it is going to be the standard of care, and insurance companies are going to have no choice but to cover it,” she said. “In the grand scheme, sofosbuvir is still less expensive than the cost of a liver transplant or the treatment for someone with liver cancer.”
In the case of the Vietnamese patient, he may be a candidate for sofosbuvir used off-label as well, Spooner said.
More hepatitis C drugs are in the pipeline and expected to become available early next year, she said. So if a patient’s treatment of interferon and ribavirin fails, it doesn’t necessarily mean future failure is inevitable.
“Pharmacists can play a really big role in helping determine patients’ drug regimens and in teaching patients about the importance of taking [their medications] every day, as well as how to avoid side effects,” said Spooner.