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AIDS 2012: Adding Nitazoxanide Does Not Improve Interferon Cure Rate for HIV/HCV Coinfected Patients

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Addition of the anti-protozoal drug Nitazoxanide (Alinia) to pegylated interferon plus ribavirin for treatment of chronic hepatitis C did not lead to higher likelihood of sustained virological response (SVR) in a study of people with HIV, but it may confer an advantage for people with unfavorable IL28B gene patterns, according to a study presented last month at the XIX International AIDS Conference (AIDS 2012) in Washington, DC.

Researchers suspected nitazoxanide might have activity against viral hepatitis when some AIDS patients coinfected with hepatitis B or C saw decreases in liver enzymes when they used the drug for cryptosporidiosis. Prior studies indicated that nitazoxanide improved SVR rates for HCV-monoinfected people when added to standard therapy.

Annie Luetkemeyer from the University of California at San Francisco and fellow investigators with the ACTG 5269 trial evaluated whether adding nitazoxanide would improve response to interferon-based therapy for HIV/HCV coinfected patients.

The study included 67 coinfected participants with HCV genotype 1 who had not previously been treated for hepatitis C. Most (78%) were men, 48% were black, 32% were white, and 18% were Hispanic. The median age was 50 years. More than 90% were on antiretroviral therapy for HIV, the median CD4 T-cell count was 452 cells/mm3, and 73% had undetectable HIV viral load.

In this single-arm pilot study all participants received a 4-week lead-in of 1000 mg/day nitazoxanide, then added 180 mcg/week pegylated interferon alfa-2a (Pegasys) plus 1000-1200 mg/day weight-adjusted ribavirin and continued on triple therapy for 48 weeks. There was no placebo arm; instead, response rates were compared against historical controls in a prior trial, A5178, also known as SLAM-C.

Results

  • 10.4% of patients achieved rapid virological response (RVR) at week 4.
  • 65.7% achieved early virological response (EVR) at week 12 and 38.8% achieved complete EVR.
  • 47.8% had undetectable HCV viral load at the end of treatment.
  • 32.8% of patients achieved SVR, or continued undetectable HCV RNA 6 months after completing treatment.
  • The EVR rate in A5269 was significantly higher than the 51.4% rate seen with pegylated interferon/ribavirin alone in study A5178 (P=0.03), but the SVR rate did not differ significantly from the 27.3% rate in that study (P=0.24).
  • 86% of people who achieved RVR at week 4 went on to achieve SVR.
  • 50% of people with EVR and 77% with complete EVR went on to achieve SVR, compared with just 6% of those without EVR.
  • However, SVR rates did not vary according to IL28B gene pattern, as they did in A5178.

o   C/C (favorable): 33.3% in A5269 vs 42.1% in A5178;

o   C/T (intermediate): 29.7% vs 33.3%, respectively;

o   T/T (unfavorable): 30.0% vs 4.3%, respectively.

  • Factors associated with better response included HCV genotype 1b, less fibrosis, lower baseline HCV RNA, age < 50 years, and race/ethnicity other than black, but these were not statistically significant.
  • 28% of participants stopped treatment prematurely, about 20% of them due to toxicities.
  • Nitazoxanide was generally well-tolerated and side effects were generally related to interferon or ribavirin.
  • Adverse events attributable to nitazoxanide included diarrhea and nausea.

"SVR rates on nitazoxanide added to [pegylated interferon + ribavirin] [were] not statistically greater than rates in historical controls treated with [pegylated interferon + ribavirin]," the researchers concluded.

However, while there was a trend toward better SVR for people with IL28B C/C in A5178, rates were similar in both studies for people with C/T, and response was "much better" for people with T/T when using nitazoxanide, Leutkemeyer explained.

"Nitazoxanide [is] associated with better response in those with unfavorable IL28B genotype (T/T)," but the clinical significance of this is unclear, the investigators suggested. "The role of nitazoxanide may depend on the as yet undefined role of IL28 B in interferon-free regimens."

8/24/12

Reference

V Amorosa, T Umbleja, V Johnson, A Luetkemeyer, et al. The addition of nitazoxanide to peginterferon alfa-2a and ribavirin does not significantly improve sustained virologic response in HCV treatment-naive genotype 1 HIV-1/HCV co-infected subjects: results of ACTG 5269. Abstract WEAB0103.