Early ribavirin pharmacokinetics, HCV RNA and alanine aminotransferase kinetics in HIV/HCV co-infected patients during treatment with pegylated interferon and ribavirin.
OBJECTIVE
We evaluated whether early ribavirin pharmacokinetics differ comparing hepatitis C/human immunodeficiency virus coinfected sustained virological responders and nonresponders.


METHODS
Twenty-four treatment-naive coinfected patients received pegylated-interferon alfa-2b (12 kDa) (1.5 microg/kg) once weekly plus daily ribavirin (13.6 mg/kg/d) for up to 48 weeks. Serum HCV RNA, serum alanine aminotransferase, and plasma ribavirin levels were measured frequently during the first 16 days of therapy and monthly thereafter.


RESULTS
Six patients were sustained responders. During the first 4 weeks of treatment, median plasma ribavirin levels and area under the ribavirin curve were significantly lower (p<0.0001 and p<0.01, respectively) in sustained responders compared with nonresponders. Compared to ribavirin levels at weeks 2 and 4, ribavirin levels in sustained responders continued to increase significantly until week 8 (p<0.02). At week 4, hemoglobin declines were significantly (p=0.002) greater in sustained responders than nonresponders. At week 1, serum HCV RNA levels and changes in alanine aminotransferase levels relative to baseline could identify likely responders better than plasma ribavirin levels.


CONCLUSIONS
We conjecture that intracellular ribavirin accumulation may be enhanced early in treatment in coinfected sustained responders, although this hypothesis should be investigated further. At week 1, serum HCV RNA and changes in alanine aminotransferase levels relative to baseline might identify likely responders.
Dahari
Harel
H
Theoretical Biology and Biophysics, Los Alamos National Laboratory, Los Alamos, NM, USA.
Markatou
Marianthi
M
Zeremski
Marija
M
Haller
Ivan
I
Ribeiro
Ruy M
RM
Licholai
Teresa
T
Perelson
Alan S
AS
Talal
Andrew H
AH
D000328:Adult; D000410:Alanine Transaminase / Q000097:blood; D000998:Antiviral Agents / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000627:therapeutic use; D004359:Drug Therapy, Combination; D005260:Female; D006678:HIV; D015658:HIV Infections / Q000150:complications*; D016174:Hepacivirus; D019698:Hepatitis C, Chronic / Q000150:complications / Q000188:drug therapy*; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000008:administration & dosage / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D011092:Polyethylene Glycols; D012367:RNA, Viral / Q000097:blood; D011994:Recombinant Proteins; D012254:Ribavirin / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000627:therapeutic use; D016896:Treatment Outcome
D000998:Antiviral Agents; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D012367:RNA, Viral; D011994:Recombinant Proteins; D011092:Polyethylene Glycols; D012254:Ribavirin; D000410:Alanine Transaminase; C417083:peginterferon alfa-2b