Modeling the probability of sustained virological response to therapy with pegylated interferon plus ribavirin in patients coinfected with hepatitis C virus and HIV.
BACKGROUND
A single-nucleotide polymorphism (SNP) near the IL28B gene (rs12979860) strongly predicts sustained virological response to pegylated interferon plus ribavirin (pegIFN-RBV) treatment for chronic hepatitis C virus (HCV) infection. Given that therapy is poorly tolerated and rates of response are lower in patients coinfected with HCV and human immunodeficiency virus (HIV), the recognition of predictors of response is a high priority in this population.


METHODS
A baseline noninvasive index was derived on the basis of the probability of achieving sustained virological response in a group of 159 HIV-HCV-coinfected patients treated at one clinic in Spain. The index was then validated using data from a separate cohort of 86 coinfected individuals. Only individuals who had completed a course of pegIFN-RBV therapy and had validated outcomes were considered.


RESULTS
The final score included 4 variables: 2 host-related variables (IL28B SNP rs12979860 and liver stiffness) and 2 HCV-related variables (genotype and viral load). The area under the receiver operating characteristic curve was 0.89 in the derivation group and 0.85 in the validation group.


CONCLUSIONS
The probability of achieving sustained virological response with pegIFN-RBV therapy in HIV-HCV-coinfected patients can be reliably estimated prior to initiation of therapy using an index that includes 4 noninvasive parameters.
Medrano
Jose
J
Department of Infectious Diseases, Hospital Carlos III, National Centre of Microbiology, Instituto de Salud Carlos III, Majadahonda, Madrid, Spain.
Neukam
Karin
K
Rallón
Norma
N
Rivero
Antonio
A
Resino
Salvador
S
Naggie
Susanna
S
Caruz
Antonio
A
Calvino
Aida
A
Macías
Juan
J
Benito
Jose Miguel
JM
Sánchez-Piedra
Carlos
C
Vispo
Eugenia
E
Barreiro
Pablo
P
McHutchison
John
J
Pineda
Juan Antonio
JA
Soriano
Vincent
V
D000328:Adult; D000998:Antiviral Agents / Q000627:therapeutic use*; D015331:Cohort Studies; D005260:Female; D015658:HIV Infections / Q000821:virology*; D016174:Hepacivirus / Q000235:genetics / Q000302:isolation & purification*; D019698:Hepatitis C, Chronic / Q000188:drug therapy* / Q000235:genetics / Q000276:immunology / Q000821:virology*; D006801:Humans; D007370:Interferon Type I / Q000627:therapeutic use*; D007372:Interferons; D007378:Interleukins / Q000235:genetics; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D015233:Models, Statistical; D011092:Polyethylene Glycols / Q000627:therapeutic use; D020641:Polymorphism, Single Nucleotide; D011237:Predictive Value of Tests; D012372:ROC Curve; D011994:Recombinant Proteins; D015203:Reproducibility of Results; D012254:Ribavirin / Q000627:therapeutic use*; D019562:Viral Load / Q000187:drug effects; D000095022:Interferon Lambda
D000998:Antiviral Agents; D007370:Interferon Type I; D007372:Interferons; D007378:Interleukins; D011092:Polyethylene Glycols; D011994:Recombinant Proteins; D012254:Ribavirin; C000624353:interferon-lambda, human; D000095022:Interferon Lambda