Early monitoring of ribavirin serum concentration is not useful to optimize hepatitis C virus treatment in HIV-coinfected patients.
BACKGROUND
Emerging data suggest that higher ribavirin (RBV) exposure could improve early hepatitis C virus (HCV) response. Furthermore, interindividual RBV bioavailability shows high variation, and dose-limiting haemolytic anaemia is a common adverse event. Therefore, it has been suggested that monitoring RBV serum levels could be used to drive dose modification and to optimize management of HCV-infected patients receiving combination treatment.


METHODS
To assess the effect of RBV serum levels on HCV RNA clearance at week 4 and 12 of treatment, and to determine the correlation between RBV serum concentration and haemoglobin decrease, RBV trough levels were measured by HPLC in stored serum samples obtained from 94 HCV-HIV-coinfected patients at week 4 and 12 of treatment with peginterferon-alpha2b (1.5 microg/kg/weekly) pIus ribavirin (800-1,200 mg/day).


RESULTS
The median RBV levels increased from 1.70 microg/ml at week 4 to 1.97 microg/ml at week 12 of treatment (P = 0.001) and were independently predicted by weight-adjusted dose of RBV and co-administration of tenofovir. Haemoglobin drop was higher among patients who received zidovudine and weakly correlated with RBV level. Although RBV concentration was lower in genotype 1 or 4 HCV-infected patients who cleared the virus at treatment week 4, the ability of this parameter to discriminate between responders and non-responders at treatment week 4 and 12 was poor.


CONCLUSIONS
Intracellular RBV accumulation early in treatment might improve the kinetics of HCV response in difficult to treat patients. Although this hypothesis and the potential interaction between RBV and tenofovir warrant further research, our data do not support RBV serum monitoring as a tool to optimize treatment in HCV-HIV-coinfected patients.
Crespo
Manuel
M
Infectious Diseases Department, Hospital Universitari Vail d'Hebron, Universitat Autònoma de Barcelona, Spain. mcrespo@vhebron.net
Pou
Leonor
L
Esteban
Juan I
JI
Falcó
Vicenç
V
Ribera
Esteban
E
Lopez
Rosa
R
Sauleda
Silvia
S
Curran
Adriá
A
Villar del Saz
Sara
S
Feijoo
María
M
Ocaña
Inma
I
Pahissa
Albert
A
D000998:Antiviral Agents / Q000008:administration & dosage* / Q000097:blood*; D016903:Drug Monitoring; D004359:Drug Therapy, Combination; D005260:Female; D006678:HIV; D015658:HIV Infections / Q000150:complications*; D016174:Hepacivirus / Q000235:genetics / Q000302:isolation & purification; D006526:Hepatitis C / Q000150:complications* / Q000188:drug therapy*; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000627:therapeutic use; D008297:Male; D012367:RNA, Viral / Q000097:blood; D011994:Recombinant Proteins; D012254:Ribavirin / Q000008:administration & dosage / Q000097:blood*; D016896:Treatment Outcome; D019562:Viral Load
D000998:Antiviral Agents; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D012367:RNA, Viral; D011994:Recombinant Proteins; D012254:Ribavirin