Effect of Baseline CD4 Cell Count on the Efficacy and Safety of Peginterferon Alfa-2a (40KD) Plus Ribavirin in Patients With HIV/Hepatitis C Virus Coinfection

Division of Infectious Diseases and Hospital Epidemiology, University Hospital Zurich, Zurich, Switzerland.
JAIDS Journal of Acquired Immune Deficiency Syndromes (Impact Factor: 4.56). 02/2008; 47(1):36-49. DOI: 10.1097/QAI.0b013e31815ac47d
Source: PubMed


The impact of baseline CD4 status on hepatitis C virus (HCV) treatment response among patients with HIV/HCV coinfection was investigated using data from a randomized study of peginterferon alfa-2a (40KD) + ribavirin (Peg-IFN/RBV).
Of 860 patients treated with conventional interferon alfa-2a + ribavirin (IFN/RBV), peginterferon alfa-2a (40KD) + placebo (Peg-IFN), or Peg-IFN/RBV for 48 weeks, 857 patients had baseline CD4 data available and were included in the analysis. Efficacy and safety were analyzed according to baseline CD4 status as absolute cell count and proportion of total lymphocytes.
Sustained virologic response (SVR) rates were highest with Peg-IFN/RBV across all CD4 strata. With Peg-IFN/RBV, SVR rates were independent of baseline CD4 in genotype 2/3 patients, but in genotype 1 patients, they tended to be higher with higher CD4 or CD4%. Frequencies of adverse events (AEs) and serious AEs were similar among treatment arms and CD4 strata. Withdrawal and dose reduction rates attributable to safety were highest with CD4 <200 cells/muL.
Peg-IFN/RBV could be effective and well tolerated in HIV/HCV-coinfected individuals with stable HIV. With Peg-IFN/RBV, response tended to increase with higher CD4 counts in genotype 1; however, because of the paucity of patients with CD4 <200 cells/muL, these data require corroboration.

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    • "Results of investigations of impact of baseline CD4 count on viral response kinetics are mixed. In a large randomized study of pegIFN + RBV in co-infected patients that included a small number of patients with CD4 counts <200 cells/μL, SVR rates tended to increase with higher CD4 counts in genotype 1, but were independent of baseline CD4 counts for genotypes 2/3 [83]. Another large randomized study of co-infected patients found the efficacy of pegIFN + RBV was not different in patients with and without severe immunodeficiency, suggesting that advanced immunosuppression is not a major factor in predicting SVR [84]. "
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    • "Therefore, if HIV infection is not advanced and there is no indication for HAART in the presence of high CD4-counts (> 500/μl), a treatment of chronic hepatitis C infection should be started prior to initiation of HAART [29]. In a recent analysis of one of the largest studies on the treatment of HIV-infected with HCV infection, the APRICOT study, a relative CD4-cell count above 25% was associated with better treatment outcome than lower CD4-cell counts and initiation of HAART is strongly recommended prior to HCV therapy if the CD4-cell count is < 350/μl [30]. Anti-HCV therapy in HIV co-infected individuals has been shown to be complicated by additive drug toxicities of pegylated interferon and ribavirin with the antiretroviral nucleosides didanosine [31,32], zidovudine [33-35] and stavudine [36]. "
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