Utility of hepatitis C viral load monitoring on direct-acting antiviral therapy.
BACKGROUND
Hepatitis C virus (HCV) RNA loads serve as predictors of treatment response during interferon-based therapy. We evaluated the predictive ability of HCV RNA levels at end of treatment (EOT) for sustained virologic response (SVR12) during interferon-sparing direct-acting antiviral therapies.


METHODS
HCV genotype 1-infected, treatment-naive patients were treated with sofosbuvir and ribavirin for 24 weeks (n = 55), sofosbuvir and ledipasvir for 12 weeks (n = 20), sofosbuvir, ledipasvir, and GS-9669 for 6 weeks (n = 20), or sofosbuvir, ledipasvir, and GS-9451 for 6 weeks (n = 19). Measurements of HCV RNA were performed using the Roche COBAS TaqMan HCV test and the Abbott RealTime HCV assay. Positive predictive value (PPV) and negative predictive value (NPV) of HCV RNA less than the lower limit of quantification (<LLOQ) at EOT for SVR12 were calculated.


RESULTS
All 55 patients treated with sofosbuvir and ribavirin had HCV RNA <LLOQ at EOT by the Roche and Abbott assays, but only 38 achieved SVR12 (PPV, 69%). Among patients treated with sofosbuvir and ledipasvir with or without GS-9669 or GS-9451, 100% (59/59) had HCV RNA <LLOQ by the Roche assay and 1 relapsed (PPV, 98%). By the Abbott assay, 90% (53/59) had HCV RNA <LLOQ, of whom 1 patient relapsed (PPV, 98%). Notably, 6 patients with HCV RNA ≥LLOQ at EOT (range, 14-64 IU/mL) achieved SVR12 (NPV, 0%). Quantifiable HCV RNA (range, 15-57 IU/mL) was measured 2 weeks posttreatment in 4 individuals, and 4 weeks posttreatment in 1 patient (14 IU/mL).


CONCLUSIONS
Contrary to past experience with interferon-containing treatments, low levels of quantifiable HCV RNA at EOT do not preclude treatment success.
Critical Care Medicine Department, National Institutes of Health Clinical Center, National Institutes of Health, Bethesda.
Sreetha
S
Sidharthan
Critical Care Medicine Department, National Institutes of Health Clinical Center, National Institutes of Health, Bethesda.
Anita
A
Kohli
Critical Care Medicine Department, National Institutes of Health Clinical Center, National Institutes of Health, Bethesda.
Zayani
Z
Sims
Institute of Human Virology, University of Maryland, Baltimore Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland.
Amy
A
Nelson
Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland Gilead Sciences Inc, Foster City, California.
Anu
A
Osinusi
Critical Care Medicine Department, National Institutes of Health Clinical Center, National Institutes of Health, Bethesda.
Henry
H
Masur
Institute of Human Virology, University of Maryland, Baltimore Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland.
Shyam
S
Kottilil
D000328:Adult; D000368:Aged; D000998:Antiviral Agents / Q000494:pharmacology / Q000627:therapeutic use*; D016903:Drug Monitoring / Q000379:methods*; D005260:Female; D016174:Hepacivirus / Q000187:drug effects*; D006526:Hepatitis C / Q000188:drug therapy* / Q000453:epidemiology / Q000821:virology; D006801:Humans; D008297:Male; D008875:Middle Aged; D011237:Predictive Value of Tests; D012367:RNA, Viral / Q000097:blood; D019562:Viral Load / Q000187:drug effects*
D000998:Antiviral Agents; D012367:RNA, Viral
HCV RNA; direct-acting antiviral; hepatitis C; viral load