Paper # 664
Impact of Zidovudine on Hematologic Parameters during Treatment with Peginterferon alfa-2a plus Ribavirin for Chronic Hepatitis C in HIV/HCV Co-infected Patients Enrolled in a Large Randomized Double-blind Study
M Rodriguez-Torres1, Jihad Slim*2, L Bhatti3, R Sterling4, M Sulkowski5, T Hassanein6, B Clotet7, T Branco8, S Passe9, S Stancic9, and the PARADIGM Study Investigators
1Fndn de Investigación de Diego, Santurce, Puerto Rico; 2St Michael’s Med Ctr, Newark, NJ, US; 3AIDS Hlthcare Fndn, Los Angeles, CA, US; 4Virginia Commonwealth Univ, Richmond, US; 5Johns Hopkins Univ Sch of Med, Baltimore, MD, US; 6Univ of California, San Diego, US; 7Fndn irsiCaixa, Hosp Univ Germans Trias i Pujol, Badalona, Spain; 8Hosp Fernando da Fonseca, Amadora, Portugal; and 9Roche, Nutley, NJ, US
Background: Anemia and neutropenia are reported to
be more frequent and severe in HIV-HCV co-infected patients receiving ZDV during
Peg-IFN/RBV treatment. However, it is unclear if the hematological safety
profile of ZDV with 1000/1200 mg/day RBV is similar to that with 800 mg/day
RBV dosing. We explored the safety of Peg-IFN/RBV +/- ZDV in the randomized
double-blind international PARADIGM study.
Methods: HIV-HCV (genotype 1) co-infected adults naive
to IFN-based therapy for CHC with stable HIV disease (on stable anti-retroviral
therapy [ART] or not requiring ART) and ≥100 CD4+ cells/mm3
were eligible. All patients received Peg-IFNα-2a 180 mg/wk
and were randomized (1:2) to receive 800 mg/day or 1000/1200 mg/day RBV
for 48 wks. The impact of ZDV treatment on hematologic parameters (hemoglobin
[hgb], neutrophil count) was examined.
Results: In the intent-to-treat population (n
= 410) the mean age was 45 years, the mean HCV RNA level was 6.4 log10,
30% were African American, 24% were Hispanic, 54% had an alanine
aminotransferase quotient ≤1.5, 88% were receiving ART at baseline and 6%
had <200 CD4+ cells/mm3. Among those receiving 800 mg/day
or 1000/1200 mg/day RBV, 16% and 14% were receiving ZDV, respectively. In
the safety population (table; n = 409), there was no negative impact of
concomitant administration of ZDV with Peg-IFNα-2a/RBV on neutrophils.
However, anemia was consistently more common among patients receiving Peg-IFNα-2a
and any dose of RBV in combination with ZDV. In particular, the rate of RBV
dose modifications among patients receiving 1000/1200 mg/day RBV in
combination with ZDV was almost twice as great compared with patients not
taking ZDV (45% vs 25%).
Conclusions: This analysis confirms that anemia is
more common and severe in co-infected patients on ZDV during Peg-IFN/RBV
treatment. It also confirms that ZDV used in conjunction with weight-dosed RBV
requires more dose modifications because of anemia. These results should be
used to consider ART modifications before therapy for CHC.
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