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  XIX International AIDS Conference
July 22-27, 2012
Washington, DC
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Adding Nitazoxanide to PEG/RBV Does Not Improve SVR With HIV/HCV Genotype 1
  XIX International AIDS Conference, July 22-27, 2012, Washington, DC

from Jules: I'm not convinced this therapy has any utility.

Mark Mascolini

Adding nitazoxanide to pegylated interferon plus weight-based ribavirin (PEG/RBV) did not improve sustained virologic response (SVR) in HCV treatment-naive people coinfected with HIV and HCV genotype 1, according to results of ACTG 5269 [1]. The finding contrasts with results of an earlier study showing an improved response rate with nitazoxanide plus PEG/RBV in Egyptian patients with HCV genotype 4 but without HIV [2].

Before introduction of HCV protease inhibitors, response rates to PEG/RBV remained doggedly low in HIV/HCV-coinfected people with HCV genotype 1 or 4. In ACTG 5178 [3], only 27% of coinfected people with genotype 1 had SVR to PEG/RBV. ACTG investigators conducted study 5269 to test the value of adding nitazoxanide (an antiprotozoal agent used to treat cryptosporidium) to PEG/RBV in people with previously untreated genotype 1 HCV infection [1].

Study participants took nitazoxanide at a dose of 500 mg twice daily for 4 weeks, then added PEG/IFN for another 48 weeks. The primary objectives were to evaluate complete early virologic response (cEVR, undetectable HCV RNA) and EVR (at least a 100-fold drop in HCV RNA or undetectable HCV RNA) at week 12. The researchers defined SVR as undetectable HCV RNA (below 43 IU/mL) 24 weeks after the end of treatment. They compared results with those of HIV/HCV-coinfected people in ACTG 5178 [3].

All study participants had a CD4 count above 200 while taking a stable antiretroviral regimen or no antiretrovirals. No one could take didanosine, and anyone with an opportunistic infection within 24 months was excluded.

This single-arm, phase 2 pilot study involved 67 coinfected people, 52 of them (78%) men, 48% black, 31% white, and 18% Hispanic. Median age stood at 50 years, median entry CD4 count at 452, and median HCV load at 2.4 million IU/mL. Forty-nine participants (73%) had an undetectable HIV load.

Of the 67 study participants, 7 (10.4%) achieved rapid virologic response (RVR, undetectable HCV RNA after 4 weeks of therapy), 44 (65.7%) achieved EVR, 26 (38.8%) achieved cEVR, and 32 (47.8%) achieved end-of-treatment response. Twenty-two participants (32.8%, 95% confidence interval 23.4% to 43.5%) achieved SVR, compared with 27.3% in ACTG 5178, a nonsignificant difference (P = 0.24).

Six of 7 people (86%) who achieved RVR achieved SVR, as did 22 of 44 (50%) who attained EVR and 20 of 26 (77%) who attained cEVR. Among 35 people who did not have a complete early virologic response, only 2 (6%) attained SVR.

SVR rates in ACTG 5269 and ACTG 5178 were 33% and 42% in people with the IL28B C/C genotype, 30% and 33% with a C/T genotype, and 30% and 4% with a T/T genotype. Although nitazoxanide was associated with a better response in people with the unfavorable IL28B T/T genotype, the researchers believe the clinical significance of this finding remains unclear. They suggested that "the role of nitazoxanide may depend upon the as yet undefined role of IL28b in interferon-free regimens."


1. Amorosa V, Umbleja T, Johnson V, 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. XIX International AIDS Conference. July 22-27, 2012. Washington, DC. Abstract WEAB0103.

2. Rossignol JF, Elfert A, El-Gohary Y, Keeffe EB. Improved virologic response in chronic hepatitis C genotype 4 treated with nitazoxanide, peginterferon, and ribavirin. Gastroenterology. 2009;136:856-862.

3. Sherman KE, Andersen JW, Butt AA, et al. Sustained long-term antiviral maintenance with pegylated interferon in HCV/HIV-co-infected patients (SLAM-C): early viral response and effect on fibrosis in treated and control subjects. 15th Conference on Retroviruses and Opportunistic Infections. February 3-6, 2008. Boston, Abstract 59.