Efficacy of Pegylated Interferon Plus Ribavirin Plus Nitazoxanide in HCV Genotype 4 and HIV Coinfection
Efficacy of Pegylated Interferon Plus Ribavirin Plus Nitazoxanide in HCV Genotype 4 and HIV Coinfection
Objectives: 1. Primary objective: To Evaluate the rate of sustained virological response
 (SVR) of pegylated interferon alfa-2b (Peg-IFN) plus ribavirin (RBV) plus nitazoxanide (NTZ)
 in patients coinfected by HIV and HCV genotype 4 (HCV-4), never treated before (naïve) and
 with a treatment failure to a standard therapy with Peg-IFN plus RBV (experienced), and to
 compare it with the rate of SVR of these patients with Peg-IFN plus RBV is a historical
 cohort. 2. Secondary objectives: In naive, as well as in experienced patients: a) To evaluate
 the virological activity at weeks 4 and 12 after starting the combination of Peg-IFN plus RBV
 plus NTZ in HIV/HCV-4-coinfected patients. b) To analyze the safety of Peg-IFN plus RBV plus
 NTZ in HIV/HCV-4-coinfected patients.

 Design: Pilot clinical trial without control to evaluate efficacy and safety (phase II).

 Patients: Individuals with HIV infection and with confirmed chronic HCV infection.

 Treatment: NTZ 500 mg every 12 hours during 4 weeks, followed by NTZ 500 mg every 12 hours
 plus Peg-IFN plus weigh-adjusted RBV for 48 weeks. Total duration of therapy: 52 weeks.

 Primary variable: The proportion of patients with HCV RNA ≤10 IU/ml 24 weeks after finishing
 the programmed length of treatment.

 Secondary variables: 1. The frequency of individuals with HCV RNA ≤10 IU/ml 12 weeks after
 finishing the programmed length of treatment. 2. The proportion of patients with HCV RNA ≤10
 IU/ml at 4 and 12 weeks after adding PegIFN plus RBV to NTZ. 3. The frequency of severe
 adverse events.
Main Objective To evaluate the SVR rate of treatment with Peg-IFN alfa-2b plus RBV and NTZ in
 patients coinfected with HIV and HCV genotype 4, both never exposed to therapy against HCV or
 who failed a previous treatment with Peg-IFN plus RBV, and to compare with the SVR rate
 obtained in patients with Peg-IFN plus RBV in a historical cohort.

 Secondary objectives: In naive, as well as in experienced patients:

 1. To evaluate the virological activity at weeks 4 and 12 after starting the combination of
 Peg-IFN plus RBV plus NTZ in HIV/HCV-4-coinfected patients.

 2. To analyze the safety of Peg-IFN plus RBV plus NTZ in HIV/HCV-4-coinfected patients.

 Design Single arm pilot clinical trial to evaluate safety and efficacy (phase II).

 Disease or disorder under study Coinfection with HIV and HCV genotype 4.

 Drugs under study Nitazoxanide 500 mg every 12 hours for 4 weeks followed by nitazoxanide 500
 mg every 12 hours plus pegylated interferon alfa-2b 1.5 mcg/kg/week and weight-adjusted
 ribavirin for 48 weeks.

 Study Population and total number of subjects Patients infected with HIV-1 with chronic HCV
 genotype 4 who meet the selection criteria.

 Number of patients included in the study: 45.
Inclusion Criteria:

 1. HIV infection.

 2. Infection with HCV genotype 4.

 3. No prior treatment with any interferon or no response to a previous treatment with
 Peg-IFN plus RBV. The lack of response will include both nonresponders, and those who
 showed relapse.

 4. Stable antiretroviral therapy 24 weeks before starting the study drugs, with
 undetectable plasma HIV RNA during that period of time.

 5. Commitment to use two non-hormonal contraception during the study and up to 24 weeks
 after treatment.

 6. Acceptance to give written informed consent to participate in the trial.

 Exclusion Criteria:

 1. Antiretroviral therapy including didanosine, stavudine, zidovudine and abacavir.

 2. Decompensated cirrhosis.

 3. Presence of other significant liver diseases, including chronic hepatitis or acute
 hepatitis B, acute hepatitis hepatitis A, hemochromatosis or deficiency of alpha-1
 antitrypsin.

 4. Pregnancy and lactation.

 5. Men planning pregnancy with their partners during the study and up to 24 weeks after
 treatment.

 6. Active or uncontrolled depression, other psychiatric illness, or disease during the
 previous year which may, in the investigator's opinion, prevent participation in the
 study.

 7. Previous suicide attempt.

 8. Active thyroid disease or poorly controlled with treatment.

 9. Previous autoimmune diseases such as inflammatory bowel disease, psoriasis serious, or
 rheumatoid arthritis, which may be exacerbated by interferon.

 10. Chemotherapy or immunomodulatory 24 weeks before starting the study.

 11. Serious illness, including cancer or unstable coronary disease, 24 weeks before
 starting the study.

 12. Any chronic disease which, in the opinion of the investigator, may prevent complete
 the study.

 13. Presence of acute or active opportunistic infections 48 weeks before starting the
 study.

 14. Evidence of hepatocellular carcinoma or alpha-fetoprotein levels ≥ 50 ng / ml, unless
 an imaging technique shows no evidence of liver tumor, all obtained 24 weeks before
 starting the study.

 15. Hemoglobinopathy or other conditions that may facilitate hemolysis.

 16. Solid organ or bone marrow transplant.

 17. Known hypersensitivity to any of the drugs under study.

 18. Active consumption of drugs or alcohol in the opinion of the investigator would
 interfere with participation in the study. The use of methadone or other opiate
 replacement therapy is not considered an exclusion criterion.

 19. Serious side effects from treatment with Peg-IFN plus RBV in patients with prior
 failure of such treatment.