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Background:  HCV/HIV co-infected patients have diminished HCV virologic response to standard interferon-based therapies.  We hypothesized that priming of immune responses to HCV might enhance response to standard HCV therapy.  We conducted a pilot study to test the safety of a novel approach of initial immunostimulatory therapy with IL-2 followed by PEG-IFN/RBV plus IL-2.

Methods:  Twenty-three HCV/HIV co-infected subjects with CD4 > 300 cells/mL and naive to HCV therapy initiated IL-2 1.2 MIU/m² subcutaneously once a day for 12 weeks followed by the addition of PEG-IFN 1.5 mg/kg once a week and RBV 800 to 1400 mg/day (based on weight) for an additional 48 weeks.  The primary endpoint in this pilot trial was permanent treatment discontinuation prior to wk 24 due to toxicity/intolerance.  End-of-treatment (week 60) results are presented herein with virologic response defined as HCV RNA <100 copies/mL (intent-to-treat). 

Results:  Subjects were 83% male; 65% white, 30% black; and had a median age of 44 years.  Median baseline values were: CD4 648 cells/mL and HCV RNA 7.5 million copies/mL.  Twenty (87%) subjects had HIV RNA < 400 copies/mL at baseline.  The majority of subjects (83%) were HCV genotype 1a or 1b.  Two (9%) subjects discontinued treatment before week 12 (while receiving only IL-2), 6 (26%) before week 24, and 11 (48%) before week 60.  Discontinuations prior to week 12 were due to suicide (n = 1) and low grade toxicity/subject decision (n = 1). Discontinuations after week 12 were due to grade 4 anemia (n = 1), non-response (n = 1), nonadherence (n = 1), and subject decision (n = 6). Grade 3 or 4 adverse events were:  fatigue (n = 2), pain (n = 1), diarrhea (n = 1), nausea/vomiting (n = 1), neutropenia (n = 5), anemia (n = 1), and hyperglycemia (n = 1).  At week 60, 5 of 23 (22%; 95%CI: 7 to 44%) had viral response.  Median change in HCV RNA from baseline to week 60 was -0.71 log₁₀ copies/mL, and 6 (27%) had > a 2-log drop at week 60.  Of the 17 subjects with ALT elevations at study entry, 13 had measurements available at week 60; of these, 6 (46%) were normal.  Median changes in CD4 count were +11, -102, -78, and -121 at weeks 12, 24, 36, and 60.

Conclusions:  Low-dose IL-2 plus PEG-IFN and RBV was associated with a high discontinuation rate and did not enhance treatment efficacy in this pilot study.  Although this study was not powered for efficacy, confidence intervals surrounding the treatment response rate suggest that this strategy should not be pursued in larger trials.

Keywords: hepatitis C; treatment; IL-2