Addition of nitazoxanide to PEG-IFN and ribavirin to improve HCV treatment response in HIV-1 and HCV genotype 1 coinfected persons naïve to HCV therapy: results of the ACTG A5269 trial.

TitleAddition of nitazoxanide to PEG-IFN and ribavirin to improve HCV treatment response in HIV-1 and HCV genotype 1 coinfected persons naïve to HCV therapy: results of the ACTG A5269 trial.
Publication TypeJournal Article
Year of Publication2013
AuthorsAmorosa VK, Luetkemeyer A, Kang M, Johnson VA, Umbleja T, Haas DW, Yesmin S, Bardin MC, Chung RT, Alston-Smith B, Tebas P, Peters MG
JournalHIV Clin Trials
Volume14
Issue6
Pagination274-83
Date Published2013 Nov-Dec
ISSN1528-4336
KeywordsAdult, Animals, Antiviral Agents, Drug Therapy, Combination, Female, Hepacivirus, Hepatitis C, HIV Infections, HIV-1, Humans, Interferon-alpha, Male, Middle Aged, Pilot Projects, Polyethylene Glycols, Recombinant Proteins, Ribavirin, Thiazoles
Abstract

BACKGROUND: We hypothesized that nitazoxanide (NTZ) added to pegylated interferon alfa-2a (PEG-IFN) and weight-based ribavirin (WBR) would improve hepatitis C virus (HCV) virologic responses in HCV treatment-naïve HIV-1/HCV genotype 1 coinfected persons.

METHODS: Prospective, single-arm study in which subjects received 4-week lead-in (NTZ 500 mg twice daily) followed by 48 weeks of NTZ, PEG-IFN, and WBR. We compared the HCV virologic responses of these subjects to historical controls from the completed ACTG study A5178 who received PEG-IFN and WBR and had similar subject characteristics. Primary endpoints were early virologic response and complete early virologic response (EVR and cEVR).

RESULTS: Among 67 subjects (78% male; 48% Black; median age, 50 years), EVR was achieved in 65.7% (90% CI, 55.0%-75.3%), cEVR in 38.8% (28.8%-49.6%). and SVR in 32.8% (23.4%-43.5%). EVR was higher with NTZ (51.4% in A5178; P = .03), but the sustained virologic response (SVR) proportion was similar (27.3% in A5178; P = .24). In contrast to A5178, SVR was similar across IL28B genotypes. Overall, NTZ was safe and well-tolerated.

CONCLUSION: Whereas EVR proportion improved significantly in this pilot study, the addition of NTZ to PEG-IFN/WBR did not significantly improve SVR compared to historical controls. NTZ may be associated with an attenuation of the effect of IL28B on HCV treatment response.

DOI10.1310/hct1406-274
Alternate JournalHIV Clin Trials
PubMed ID24334180
PubMed Central IDPMC4113390
Grant List1-UO1-AI069503 / AI / NIAID NIH HHS / United States
1U01AI068634 / AI / NIAID NIH HHS / United States
1U01AI068636 / AI / NIAID NIH HHS / United States
1U01AI069472 / AI / NIAID NIH HHS / United States
5 UL1 RR021456-07 / RR / NCRR NIH HHS / United States
5U01 AI069470-01 / AI / NIAID NIH HHS / United States
5UM1 AI069415-06 / AI / NIAID NIH HHS / United States
5UM1 AI06953-07 / AI / NIAID NIH HHS / United States
5UO1 AI069502-06 / AI / NIAID NIH HHS / United States
7UM1AI068636 / AI / NIAID NIH HHS / United States
AI 069424 / AI / NIAID NIH HHS / United States
AI050410 / AI / NIAID NIH HHS / United States
AI069419 / AI / NIAID NIH HHS / United States
AI069423 / AI / NIAID NIH HHS / United States
AI069501 / AI / NIAID NIH HHS / United States
AI069556 / AI / NIAID NIH HHS / United States
AI69432 / AI / NIAID NIH HHS / United States
P30 AI050410 / AI / NIAID NIH HHS / United States
P30 DK026743 / DK / NIDDK NIH HHS / United States
P30AI27767-24 / AI / NIAID NIH HHS / United States
R01 AA012879 / AA / NIAAA NIH HHS / United States
RR 025747 / RR / NCRR NIH HHS / United States
RR024996 / RR / NCRR NIH HHS / United States
U01 AI027663 / AI / NIAID NIH HHS / United States
U01 AI068634 / AI / NIAID NIH HHS / United States
U01 AI068636 / AI / NIAID NIH HHS / United States
U01 AI069452 / AI / NIAID NIH HHS / United States
U01- A1069472 / / PHS HHS / United States
U01-AI-096497 / AI / NIAID NIH HHS / United States
U01AI069511-02 / AI / NIAID NIH HHS / United States
UL1 RR 024160 / RR / NCRR NIH HHS / United States
UL1 TR000439 / TR / NCATS NIH HHS / United States
UL1 TR000457 / TR / NCATS NIH HHS / United States
UL1-TR00058 / TR / NCATS NIH HHS / United States
UL1RR024989 / RR / NCRR NIH HHS / United States
UM1 AI068636 / AI / NIAID NIH HHS / United States
UM1 AI069412 / AI / NIAID NIH HHS / United States
UM1 AI069423 / AI / NIAID NIH HHS / United States
UM1 AI069496 / AI / NIAID NIH HHS / United States
UM1 AI069534 / AI / NIAID NIH HHS / United States