904 
Predictive Factors of Severe Toxicity Associated with Pegylated Interferon and Ribavirin Treatment in HIV/HCV-co-infected Patients
José A. Mira*1, B Valera-Bestard2, A Arizcorreta-Yarza3, D Merino4, A Rivero5, A Collado6, M Ríos-Villegas7, J Ruíz-Morales8, J Macías1, J Pineda1, and Grupo Andaluz para el Estudio de las Enfermedades Infecciosas (GAEI)
1Hosp Univ de Valme, Sevilla, Spain; 2Hosp Univ Virgen del Rocio, Sevilla, Spain; 3Hosp Univ Puerta del Mar, Cadiz, Spain; 4Hosp Juan Ramon Jimenez, Huelva, Spain; 5Hosp Univ Reina Sofía, Cordoba, Spain; 6Hosp Torrecardenas, Almeria, Spain; 7Hosp Univ Virgen Macarena, Sevilla, Spain; and 8Hosp Univ Virgen de la Victoria, Malaga, Spain
Background: Dose reductions or premature discontinuation
of treatment due to severe adverse effects related to pegylated interferon (pegIFN)
+ ribavirin (RBV) is relativately common among HIV/hepatitis C virus (HCV) -co-infected
patients. However, the possible risk factors of severe toxicity associated to pegIFN
+ RBV treatment are unknown. The aim of our study was to identify predictive
factors associated with severe toxicity secondary to the combination of pegIFN +
RBV in HIV-infected patients with chronic HCV.
Methods: All HIV/HCV-co-infected patients who received at least 1 dose of pegIFN-α-2a
(180 µg weekly) or pegIFN-α-2b (1.5 µg/Kg weekly) + RBV (800 to 1200
mg/day) from June 2000 to February 2006, at 8 hospitals in Spain, were
included in the study. Severe toxicity associated with pegIFN + RBV combination
was defined as an episode of laboratory abnormality (hemoglobin level <10
g/dL, neutrophils <750 /mm3, platelets <50,000/mm3 or
thyroid stimulating hormone >10 mIU/mL) or clinical side effect that led to permanent
discontinuation of treatment. Univariate
and multiple logistic regression analysis were performed to determine baseline
variables associated with severe toxicity, including hematological levels, use
of specific ART drugs and those related with anti-HCV therapy.
Results: We included in this study 242 HIV/HCV-co-infected
patients. A total of 203 (84%) subjects received ART. Sustained virological
response and premature discontinuation of therapy due to adverse events were
observed in 87 (35%) and 31 (13%) individuals, respectively: 106 patients (44%) developed any event of
severe toxicity. Neutropenia (18%) and influenza-like syndrome (4%) were the most
frequent severe laboratory abnormality and clinical adverse event, respectively.
In the multivariate analysis, zidovudine treatment (adjusted odds ratio [AOR]
3.0, 95%CI 1.5 to 6.2), didanosine treatment (3.0, 95%CI 1.0 to 9.1), cirrhosis
(AOR 3.0, 95%CI 1.2 to 7.2), history of depression (AOR 6.4, 95%CI 2.0 to 20.3),
and baseline hemoglobin level < 14 g/dL (AOR 3.3, CI 1.6 to 6.8) were
associated with severe toxicity.
Conclusions: ART regimens including zidovudine or didanosine, liver cirrhosis, baseline
hemoglobin level of <14 g/dL, and a history of depression are predictive
factors of severe toxicity secondary to pegIFN + RBV among HIV/HCV-co-infected
patients.
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