Low response to pegylated interferon plus ribavirin in HIV-infected patients with chronic hepatitis C treated with abacavir.
BACKGROUND
There is little information about the influence of antiretroviral drugs on the antiviral activity of pegylated interferon (PEG-IFN) plus ribavirin (RBV) against hepatitis C virus (HCV).


METHODS
All HIV-infected patients with chronic hepatitis C who received first-line PEG-IFN plus RBV were retrospectively analyzed. Only patients in whom virological stopping rules were applied and who did not change their antiretrovirals were chosen. Plasma RBV concentrations were measured at week 4.


RESULTS
A total of 493 patients (78% males, mean age 41 years, 78% on antiretroviral therapy, mean CD4+ T-cell count 561 cells/microl) fit the study inclusion criteria. Mean baseline serum HCV RNA was 5.89 log10 IU/ml, 65% were infected by genotypes 1 or 4 and 40% had advanced liver fibrosis (Metavir F3F4). The overall rate of sustained virological response (SVR) was 38%. Factors associated with lack of SVR in the multivariate analyses (odds ratio [95% confidence interval], P-value) were higher baseline serum HCV RNA (2.42 per log10 IU/ml [1.31-4.46], 0.005), HCV genotypes 1 or 4 (5.95 [2.50-14.29], < 0.001) and lower RBV plasma trough concentrations (1.74 per microg/ml [1.15-2.63], 0.009). Interestingly, a trend was noticed for abacavir use (2.22 [0.91-5.40], 0.08), which become significant when only considering the subset of patients with RBV plasma levels < 2.3 microg/ml (7.63 [1.39-41.67], 0.02).


CONCLUSIONS
The use of abacavir might interfere with the anti-HCV activity of PEG-IFN plus RBV. As both antivirals are guanosine analogues, an inhibitory competition between abacavir and RBV might explain this observation, which is more prominent in patients with lower RBV exposure.
Vispo
Eugenia
E
Hospital Carlos III, Madrid, Spain.
Barreiro
Pablo
P
Pineda
Juan A
JA
Mira
José A
JA
Maida
Ivana
I
Martín-Carbonero
Luz
L
Rodríguez-Nóvoa
Sonia
S
Santos
Ignacio
I
López-Cortes
Luis F
LF
Merino
Dolores
D
Rivero
Antonio
A
Soriano
Vincent
V
D000328:Adult; D000998:Antiviral Agents / Q000097:blood / Q000627:therapeutic use*; D015224:Dideoxynucleosides / Q000627:therapeutic use*; D004347:Drug Interactions; D004359:Drug Therapy, Combination; D015658:HIV Infections / Q000150:complications / Q000188:drug therapy* / Q000821:virology; D016174:Hepacivirus / Q000187:drug effects / Q000235:genetics; D019698:Hepatitis C, Chronic / Q000150:complications / Q000188:drug therapy* / Q000235:genetics; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000627:therapeutic use*; D008297:Male; D016017:Odds Ratio; D011092:Polyethylene Glycols / Q000627:therapeutic use*; D012367:RNA, Viral / Q000097:blood; D011994:Recombinant Proteins; D012189:Retrospective Studies; D018894:Reverse Transcriptase Inhibitors / Q000627:therapeutic use*; D012254:Ribavirin / Q000097:blood / Q000627:therapeutic use*; D018570:Risk Assessment; D013030:Spain; D017211:Treatment Failure; D019562:Viral Load; D000099227:Abacavir
D000998:Antiviral Agents; D015224:Dideoxynucleosides; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D011092:Polyethylene Glycols; D012367:RNA, Viral; D011994:Recombinant Proteins; D018894:Reverse Transcriptase Inhibitors; D012254:Ribavirin; D000099227:Abacavir; C417083:peginterferon alfa-2b; C100416:peginterferon alfa-2a