Dose adjustment of ribavirin
Anaemia is a common side-effect of RBV therapy and dose adjustment is often required. Patients whose haemoglobin Hb level falls below 10 gdL should have
their RBV dose reduced. A patient whose Hb level falls below 8.5 gdL should discontinue therapy. For patients with a history of stable cardiovascular disease,
RBV dose reduction is required if the Hb decreases by ≥2 gdL during any
4-week period. In addition, for these patients, if the Hb remains 12 gdL after 4 weeks on a reduced dose, the patient should discontinue combination therapy.
The dose of RBV in patients with renal failure must also be adjusted; patients with creatinine clearance 50 mLmin should not be treated with RBV and those
on dialysis must have the dose lowered to 200 mg per day or take it three times per week. Increased monitoring is required in this group.
Dose adjustment of interferon
Discontinuation of PEG-IFN α2b is recommended if the Hb is 8.5 gdL or 12
gdL after 4 weeks of dose reduction in patients with cardiac failure, total white blood cell count 1.0 x 10
9
L, neutrophil count 0.5 x 10
9
L, platelet count 25 x 10
9
L in patients with genotype 1 infection or 50 x 10
9
L in those with non- genotype 1 infection, bilirubin direct 2.5 x upper limit of normal, total bilirubin
4 mgdL for 4 weeks, creatinine 2.0 mgdL or ALTAST 2 x baseline and 10 x upper limit of normal.
Discontinuation of PEG-IFN α2a is recommended if the platelet count is 25 x
10
9
L, Hb 8.5 gL or the Hb is 12 gdL despite 4 weeks of dose adjustment in patients with cardiac failure.
In patients with end-stage renal disease creatinine clearance 20–40 mLmin, a starting dose of PEG-IFN
α2a of 135 μg once a week should be used.
8.3 Monitoring for efficacy
Stopping rules and recommended duration of treatment depends on the stage of disease cirrhosis versus mild-to-moderate disease, previous treatment
failure response null response, partial response or relapse, genotype and on the results of HCV viral load testing while on treatment Figure 8.2. Treatment
recommendations on stopping rules and monitoring for eficacy are illustrated further in Appendix 5 for persons with genotype 1 infection receiving PEG-IFN
RBV and either boceprevir or telaprevir. Longer treatment regimens may be given in slow virological responders and persons with HIV or cirrhosis. For example, in
the PRESCO study, higher weight-based dosing of RBV was used and treatment duration was extended from 48 to 72 weeks. This improved the SVR rate in
genotype 1-infected HIV-positive persons 53 versus 31.
189
Premature
treatment discontinuation was common, however, and occurred in 45 in the prolonged treatment arm 2.6 due to severe anaemia. Extension of treatment
duration from 24 to 48 weeks in genotype 23 infection also resulted in a higher SVR rate 82 versus 67.
FIGURE 8.2A
Duration of pegylated interferon and ribavirin therapy for infection with HCV genotypes 1 and 4
FIGURE 8.2B
Duration of pegylated interferon and ribavirin therapy for genotypes 2, 3, 5 and 6
PEG-IFN and RBV used in combination to treat genotypes 1 and 4 chronic HCV infection may be given for varying durations depending on treatment response. If the viral load drops less than 2 log at 12 weeks or is detectable at 24 weeks of therapy, treatment should be
stopped. An extended rapid virological response eRVR is associated with a high likelihood of SVR and therefore a reduced treatment duration of 24 weeks can be considered if the baseline viral load is 400 000–800 000 IUmL. Conversely, if patients have a slow virological
response with a detectable viral load at 12 weeks of treatment and a ≥2 log drop with a negative viral load at week 24 delayed virological
response; DVR, a prolonged 72-week course of therapy can be considered.
Pegylated IFN and RBV used in combination to treat chronic HCV infection with genotypes 2, 3, 5 and 6 may be given for varying durations depending on treatment response. If the viral load drops by less than 2 log at 12 weeks or is detectable at 24 weeks of therapy, treatment
should be stopped. An extended rapid virological response eRVR is associated with a high likelihood of SVR and therefore a reduced treatment duration of 24 weeks can be considered. Conversely, if patients have a slow virological response with a detectable viral load at
12 weeks of treatment and a ≥2 log drop with a negative viral load at week 24 delayed virological response; DVR, a prolonged 48-week
course of therapy can be considered. a. A shortened course of 12–16 weeks of therapy may be considered in patients with HCV genotypes 2 and 3 and an RVR there is a slight
reduction in inal SVR rates. Viral load
End of treatment if baseline Viral load 400 000-800 000 IUml
PEG-INFRBV Negative
Negative Week
24 12
4
Viral load
End of treatment
Positive Negative
Negative or
STOP treatment
Week
24 12
4
Viral load Positive
≥2log drop or STOP treatment
Negative or
STOP treatment
Week
24 12
4 48
72
End of treatment
Viral load End of treatment
Negative
a
Week
24 12
4
Viral load
End of treatment
Positive Week
24 12
4 48
PEG-INFRBV
≥2log drop or STOP treatment
Negative or
STOP treatment
9. SPECIAL CONSIDERATIONS FOR SPECIFIC POPULATIONS
