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UND during tx, DETECTED at EOT 8 years 4 weeks ago #13816
Hello, Dr. Freeman. I have a question about what happened to korean patients on generic tx. Two hard-to-explain cases happened. One patient, who is GT2a and on sof-rib, was UND at wk4, 8, but detected at wk12. Another patient, who is GT1b and on sof-led, was UND at wk4, but detected at wk12. As far as I know, these are called virus break-through. how come did it happen? what do you recommend as next-step for those who experienced virus break-through? hep-c for 20yrs. GT1a. Started twinvir(sof-led) 05/03/16. Before tx: VL=1.7mil. AST, ALT in normal range 2nd week of tx: VL <15. AST, ALT in normal range 6th week of tx: VL < 15. AST, ALT in normal range The following user(s) said Thank You: dacngvn | |
UND during tx, DETECTED at EOT 8 years 4 weeks ago #13822
Assuming that the patients were taking their medication daily, and that their medication was good quality, and that it's not a <15 detected (because this may SVR - Tina here was <15 DET at EOT, UND @ SVR2 and UND @ SVR4) Virological breakthrough happens when the patient's remaining HCV virus is not efficiently killed by the medications being taken and can continue to grow in their presence. Resistant mutants are not created by taking DAAs. They are created because the HCV replication process does not reliably produce accurate copies of the original RNA genetic code. Most of these inaccurate copies (mutants) produce nonfunctional, or poorly functional viruses, however some may be resistant to drugs. When we give drugs all the other HCV gets killed, and like weeds in a garden the mutants now have a chance to grow. Although Sofosbuvir resistance is rare it is possible. In the original dose scoping trial for Sofosbuvir a dose of 200 mg suppressed virus on treatment to < LLOQ for 100% , but at EOT only 94% were still < LLOQ. SVR was 90%. On the dose of 400 mg on treatment and EOT were 100%. Interestingly SVR was only 1% higher - 91% The next step for patients who have relapsed depends on how sick they are. If they are not sick careful consideration should be given to waiting - as more people fail DAAs we learn more. If they are sick and must be treated urgently: 1b - Sof+Dac+/-Riba, Sof+Dac+Simeprevir or Viekira Pak would be reasonable options 2 - Sof+Dac+/-Riba, Sof+Dac+Simeprevir would be a reasonable options (note that the total reported trials for Sof+Dac in GT2 are 49/53 although I have some unpublished data that will increase those numbers) Note that Simprevir is active against all but GT3 - www.catie.ca/en/treatmentupdate/treatmen...ifferent-strains-hcv (GT1 is not mentioned but it is in the guidelines for GT1 with Sof) In broad terms for retreatment we would pick at least one, probably 2, and maybe all 3 of: 1) Use different drug(s) - the resistance profile for each varies a bit 2) Treat for longer 3) Add something extra - (proven) Riba, Simeprevir (not GT3), or (experimental) Chlorcyclizine YMMV | |
UND during tx, DETECTED at EOT 8 years 4 weeks ago #13823
I appreciate it, Dr. Freeman. I will let them know your advice. As far as I know, the doctor who takes care of 1b patient decides to treat him with sof-led for more 12wks, adding ribavirin. hopefully, they will get cured next time. jay hep-c for 20yrs. GT1a. Started twinvir(sof-led) 05/03/16. Before tx: VL=1.7mil. AST, ALT in normal range 2nd week of tx: VL <15. AST, ALT in normal range 6th week of tx: VL < 15. AST, ALT in normal range | |
UND during tx, DETECTED at EOT 8 years 4 weeks ago #13827
Daclatasvir is active against L31M mutation. Ledipasvir is not, so Daclatasvir is better. 12 weeks + Riba is only one change - 2 changes would be better - Daclatasvir or 24 weeks (or both). Resistance Profiles:
YMMV | |
UND during tx, DETECTED at EOT 8 years 4 weeks ago #13828
Thank you, Dr. Freeman. I will let the patient know Dac is more rational choice than 12wks Sof/Led + Riba. I just got news about the GT2 patient who was detected at EOT. She went to another lab to get blood test again, and found previous test result to be wrong. Now UND. good for her. Thank you for your kind advice, Dr Freeman hep-c for 20yrs. GT1a. Started twinvir(sof-led) 05/03/16. Before tx: VL=1.7mil. AST, ALT in normal range 2nd week of tx: VL <15. AST, ALT in normal range 6th week of tx: VL < 15. AST, ALT in normal range The following user(s) said Thank You: Hazel | |
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