The prevalence of recurrent viremia was low among patients with hepatitis C who achieved sustained virologic response, data from a recently published study demonstrate.
Among those patients who did experience late recurrent viremia, most had HCV reinfection.
“In recent years, direct antiviral agent therapy has dramatically enhanced rates of sustained virologic response to [more than] 90% of patients with chronic HCV infection,” Infectious Disease News Editorial Board Member Mark S. Sulkowski, MD, of Johns Hopkins University School of Medicine, and colleagues wrote. “To determine true treatment efficacy and to define the most appropriate retreatment for patients with recurrent viremia, it is important to distinguish virologic relapse from reinfection where patients who achieve HCV eradication during treatment become infected with a new HCV strain posttreatment.”
Mark S. Sulkowski
Researchers performed sequencing analyses on 3,004 patients from 11 phase 3 trials of sofosbuvir (Sovaldi, Gilead Sciences) or sofosbuvir and ledipasvir (Harvoni, Gilead). Sulkowski and colleagues defined sustained virologic response as having no detectable HVC RNA 12 weeks after completing treatment; late recurrent viremia was defined as having no HVC RNA 12 weeks after treatment, but a recurrence of HVC at 24 weeks of follow-up. Across all 11 trials, there was a 99.7% concordance between virologic response at 12 and 24 weeks, the researchers wrote.
Twelve patients across all trials had late recurrent viremia, 11 of whom had the same HCV subtype at baseline and at recurrence. Phylogenetic analysis showed that of these 12 patients, seven (58%) of those who achieved HCV eradication later became reinfected with a different strain, according to Sulkowski and colleagues, and five experienced relapse from viruses that continued throughout treatment in the liver or another compartment, but re-emerged after 24 weeks. All five who relapsed were infected with HCV genotype 3a, which researchers said was consistent with a high relapse rate of that genotype. Deep sequencing analysis did not detect any drug resistance variants among the group that relapsed.
Another five patients with late recurrent viremia were found to have a virus that was significantly unrelated to the virus they had immediately posttreatment. Four of those were reinfected with the same subtype they had at baseline, and only one patient was reinfected by a different genotype. Two were reinfected by distantly related viruses.
“Taken together, the prevalence of late recurrent viremia was low in patients achieving sustained virologic response after sofosbuvir-based therapies. Fifty-eight percent of the patients with late recurrent viremia had HCV reinfection,” Sulkowski and colleagues wrote. “This finding has implications for determining true treatment efficacy and selection of optimal retreatment strategies.” – by Andy Polhamus
Disclosure: Sulkowski reports receiving grants from AbbVie, Bristol-Myers Squibb, Gilead, Janssen, Merck and Tobira, as well as fees from AbbVie, Bristol-Myers Squibb, Clinical Care Options Cocrystal, Gilead, Janssen, Merck, Practice Point, Trek and ViralEd. Please see the full study for a complete list of all other researchers’ relevant financial disclosures.