In the Journals

HCV RNA levels during treatment not predictive of SVR12 in DAA era

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March 10, 2015

Low levels of HCV RNA at the end of treatment are not predictive of treatment response among patients with hepatitis C virus infection treated with interferon-free regimens, according to data published in Clinical Infectious Diseases.

“Patients receiving direct-acting antiviral therapy for short durations may go on to achieve a cure even if tests show the presence of low levels of HCV RNA in blood during and after treatment, Shyamasundaran Kottilil, MBBS, PhD, co-director of the Institute of Human Virology’s Clinical Research Unit at the University of Maryland, told Infectious Disease News. “This is important because in the past with interferon-based therapies, on-treatment HCV RNA levels were used to guide duration of treatment.”

Kottilil and colleagues evaluated 120 patients with HCV genotype 1 who were enrolled in one of two clinical trials. In one, 60 patients received Sovaldi (sofosbuvir, Gilead Sciences) with weight-based or low-dose ribavirin for 24 weeks. In the second trial, 60 patients were assigned Harvoni (sofosbuvir/ledipasvir, Gilead Sciences) alone for 12 weeks or with GS-9669 or GS-9451 for 6 weeks. This analysis included 114 patients with evaluable data, including HCV RNA measurements at week 4, end of treatment and 12 weeks after treatment was completed.

Shyamasundaran Kottilil

Roche’s COBAS TaqMan HCV test and the Abbott RealTime HCV assay were used to measure HCV RNA levels. Fifty of the patients (96%) treated with sofosbuvir and ribavirin had week-4 HCV RNA less than the lower limit of quantification (LLOQ) on the Roche assay, and among those, 35 achieved SVR12, a positive predictive value (PPV) of 70%. On the Abbott assay, 34 patients (62%) had an HCV RNA less than the LLOQ, and 24 met SVR12, with a PPV of 71%. The sofosbuvir/ledipasvir-based regimens had similar values.

At the end of treatment, all 55 patients who received sofosbuvir and ribavirin had an HCV RNA less than the LLOQ by both assays, but only 38 patients achieved SVR12 for a PPV of 69%. All patients treated with sofosbuvir/ledipasvir-based regimens had HCV RNA less than the LLOQ by the Roche assay, and only one relapsed for a PPV of 98%. On the Abbott assay, 53 patients (90%) had HCV RNA less than the LLOQ at the end of treatment and 52 patients achieved SVR, a PPV of 98%.

There were six patients at the end of the 6-week, sofosbuvir/ledipasvir-based regimens who had HCV RNA at or above the LLOQ at the end of treatment. All went on to achieve SVR12, four at 2 weeks post-treatment and one at 4 weeks post-treatment.

“Providers should not stop or extend therapy in patients who have detectable HCV RNA at 4 weeks into treatment with direct-acting antivirals,” Kotillil said. “This was a small study, and we would like to see these results confirmed using a larger number of patients, particularly patients who have liver cirrhosis and have prior treatment experience.” – by Emily Shafer

Disclosure: Kottilil reports no relevant financial disclosures. One of the researchers is an employee of Gilead Sciences.

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