Hepatitis C viral load testing during treatment can be used
to predict which patients have been cured after a shorter course of treatment,
potentially cutting the cost of treatment by up to half, researchers from Loyola
University Chicago report in the Journal
of Hepatology.
HCV viral load (RNA) testing is usually carried out at the
end of treatment and again 12 weeks after the completion of treatment in order
to check response and to determine whether the response to treatment has been
sustained. A sustained virological response 12 weeks after completion of treatment
(SVR12) is now considered to be evidence that hepatitis C infection is cured.
Until the introduction of direct-acting antiviral treatment,
viral load measurement during treatment and response-guided therapy were customary
in hepatitis C treatment. Lack of viral response during treatment strongly predicted
failure of interferon-based treatment and was a reason for stopping treatment.
Very high response rates to interferon-free regimens reduced interest in
measuring viral load during treatment, since early viral load changes did not
appear to predict treatment failure.
But, noting that virtually all people treated with
direct-acting antivirals have virus levels below the limit of quantification by
the end of treatment and achieve a sustained virological response 12 weeks
later, American and French researchers asked when people are cured of hepatitis
C during treatment, and whether a mathematical model derived from frequent
measurements of viral load during treatment would allow the duration of
treatment to be reduced for others, saving money on direct-acting antivirals.
The researchers used retrospective data from 58 consecutive
patients who received hepatitis C treatment with 12 weeks of treatment with sofosbuvir
and ledipasvir (n = 20), sofosbuvir and simeprevir (19) or sofosbuvir and daclatasvir
(19) at three clinics in France. Viral load was measured at baseline, day 2,
every other week, at the end of treatment and 12 weeks after completion of
treatment.
The study population included a high proportion of patients
considered harder to treat and more likely to be in need of a prolonged course
of treatment, possibly including ribavirin. 76% were treatment-experienced, 57%
had cirrhosis and 43% had advanced fibrosis (F3). Baseline viral load was high,
averaging 6.07 log IU/ml. None were treated with ribavirin. Ninety-eight per
cent were cured and one patient experienced virological relapse after
completing treatment and prior to post-treatment week 12.
Based on a median baseline viral load of 6.07 log IU/ml the
researchers calculated that it took a mean of 6.9 weeks for study participants
to be cured, with 43% clearing HCV within 6 weeks, 30% within 6-8 weeks, 13%
within 8-10 weeks and the remaining 9% within 12 weeks.
Speed of treatment response was not associated with
cirrhosis or with previous treatment response (non-response vs relapse or
previously untreated), nor with pre-treatment viral load.
Time to HCV RNA < 15 IU/ml was strongly associated with
the projected time to cure, such that 92% of those who reached HCV RNA < 15
IU/ml at day 14 would be cured by week 6 and 100% of those who reached HCV RNA
< 15 IU/ml at day 28 would be cured by week 10.
The researchers then calculated how much response-guided
therapy might save, assuming an average treatment cost of 58,671 euros per
patient based on 2015 French prices.
Adjusting treatment duration to 6 weeks for those achieving HCV
RNA < 15 IU/ml at day 15 (n = 28) would have reduced the total cost of
treatment in this cohort by 43%. Adjusting treatment duration to 10 weeks for
those achieving HCV RNA < 15IU/ml at day 28 (n = 23) would have reduced the
total cost of treatment by 17% for this group of patients. For the remainder, a
standard 12-week course of treatment would have been needed.
The study authors conclude that rather than studying shorter
durations of treatment for numerous different regimens, a response-guided treatment
model which uses viral load measurements at weeks 2 and 4 to guide the duration
of treatment may be a more rational approach to reducing the cost of treatment
and minimising adverse events.