Modeling hepatitis C virus therapies combining drugs and lectin affinity plasmapheresis.
Hepatitis C virus (HCV) infection can be cured by standard pegylated interferon (IFN) + ribavirin drug therapy in 30-50% of treatment-naïve genotype 1 HCV patients. Cure rate is defined as a sustained viral response measured 6 months after the end of treatment. Recently, Fujiwara et al. [Hepatol Res 2007;37:701-710], using a double-filtration plasmapheresis (DFPP) technique, showed that simple physical reduction in circulating HCV using a 1-week pretreatment increased the cure rate for treatment-naïve type 1 HCV patients from 50 (controls) to 78% (treated). For previous nonresponders, the cure rate increased from 30 to 71%. This effect occurs even though the DFPP per treatment HCV viral load reduction averaged 26%. In clinical studies discussed here, a lectin affinity plasmapheresis (LAP) device caused an estimated 41% decrease in viral load as previously reported. A more detailed analysis using normalized data to correct for any variations in initial viral load gave an average 29% per treatment viral load reduction in 5 HCV-positive dialysis patients. The latter data indicate that continuous application of LAP could bring HCV viral load to undetectable levels in 4.1 days. Compared to DFPP, the LAP approach has the advantage that no plasma losses are incurred. In addition hemopurification can be carried out for extended periods of time analogous to continuous renal replacement therapy for the treatment of acute kidney failure, making the process much more effective. Calculations based on these data predict that continuous hemopurification would substantially increase the rate of viral load reduction (approx. 14-fold) and therefore increase the cure rate for HCV standard-of-care drug therapies without adding additional drugs and their associated side effects.
Tullis
Richard H
RH
Aethlon Medical Inc. San Diego, Calif., USA. rhtullis@aethlonmedical.com
Duffin
R Paul
RP
Ichim
Thomas E
TE
Joyce
James A
JA
Levin
Nathan W
NW
D000998:Antiviral Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D002986:Clinical Trials as Topic; D003131:Combined Modality Therapy; D004359:Drug Therapy, Combination; D019698:Hepatitis C, Chronic / Q000150:complications / Q000188:drug therapy / Q000628:therapy*; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000008:administration & dosage / Q000627:therapeutic use*; D007676:Kidney Failure, Chronic / Q000150:complications / Q000628:therapy; D037241:Mannose-Binding Lectins / Q000494:pharmacology*; D008954:Models, Biological; D037121:Plant Lectins / Q000494:pharmacology*; D010956:Plasmapheresis / Q000379:methods*; D011092:Polyethylene Glycols / Q000008:administration & dosage / Q000627:therapeutic use*; D011994:Recombinant Proteins; D006435:Renal Dialysis / Q000379:methods; D012254:Ribavirin / Q000008:administration & dosage / Q000627:therapeutic use*; D016060:Sorption Detoxification / Q000379:methods*; D016896:Treatment Outcome; D019562:Viral Load; D014766:Viremia / Q000188:drug therapy / Q000628:therapy*
D000998:Antiviral Agents; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D037241:Mannose-Binding Lectins; D037121:Plant Lectins; D011994:Recombinant Proteins; C063117:snowdrop lectin; D011092:Polyethylene Glycols; D012254:Ribavirin; C417083:peginterferon alfa-2b