Clinical trial NCT02008214: Efficacy of PTX+IFN Alpha+ RBV on Hepatitis C Virus Coinfected HIV Patients
Official title: Efficacy of Pentoxyfylline Addition to a Treatment Scheme Based on Interferon Alpha and Ribavirin on Hepatitis C Virus Coinfected HIV Patients, Considering Interleukin 28B Polymorphism rs12979860
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE4
Conditions: Hepacivirus
HIV Infections
Keywords: Pentoxifylline
Sustained virologic response
Hepatic fibrosis
Lead sponsor: Centro Universitario de Ciencias de la Salud, Mexico
Sponsor class: OTHER
First posted: 2013-12-11
Enrollment: 60
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Current Hepatitis C virus (HCV) treatment consists of the combination of interferon alpha 2a (IFN-alpha 2a) plus ribavirin (RBV) and it provides sustained virologic responses (SVR) on 54 to 56% on HCV monoinfected patients and this response is even lower on HIV-HCV coinfected patients. A previous study on HCV monoinfected patients showed that the addition of pentoxyfylline (PTX) to a treatment scheme based on interferon-alfa and ribavirin increased SVR on 25%, although it is not known if the same effect is to be obtained in HCV-HIV coinfected patients.

On the other hand, other factors such as host genetics, have proved to influence treatment response on HCV infected patients. The best described genetic factor so far is the interleukin 28B (IL28B) polymorphism rs12979860, where a cytosine-cytosine (CC) genotype provides an almost twice increase on SVR than the rest of the genotypes.

Therefore, this is a randomized, double blind study to assess the efficacy of pentoxyfylline addition to a treatment scheme based on interferon-alfa and ribavirin in chronic HCV genotype 1, co-infected HIV-1 positive subjects, considering the IL28B polymorphism rs12979860.

HIV-HCV coinfected subjects currently receiving Highly active antiretroviral therapy (HAART), with at least 8 months on undetectable HIV viral load and T helper cells count of 200 or higher will be included. Patients will be randomized on one of two groups:

* Group A: IFN alpha 2a + RBV + PTX
* Group B: IFN alpha 2a + RBV + placebo

Patients will be followed for primary outcome during 72 (for rapid responders) or 96 weeks (for non rapid responses). Outcome measures will be the following:

* SVR rate 24 weeks after the end of treatment
* Grade of Hepatic fibrosis from baseline to the end of treatment, measured by transient elastography and the AST to platelet ratio index (APRI index)
* IL28B rs12979860 genotype

The study hypothesis is that the addition of PTX to a treatment scheme based on IFN-alfa2a and RBV in chronic HCV genotype 1, co-infected HIV-1 positive subjects will improve SVR rate and fibrosis progression irrespectively of IL28B rs12979860 genotype.


Eligibility criteria: Inclusion Criteria:

* HIV/HCV coinfected patients
* 18 to 65 years old
* currently receiving HAART
* non-pregnant women
* HIV infection controlled as: undetectable viral load (\<40 copies/mL) for at least 8 months and T helper cells count of 200 cells/μL or above
* no contraindications to IFN alpha2a, RBV or PTX treatment
* sign informed consent form
* laboratory parameters within acceptable ranges

Exclusion Criteria:

* Women that present a positive pregnancy test during the study
* Patients that for any reason no longer wish to receive IFN alpha2a, RBV or PTX treatment
* Serious adverse events that prevent to continue IFN alpha2a, RBV or PTX treatment; such as severe neutropenia, severe thrombocytopenia or severe anemia
* Presence of an opportunistic infection or malignancy that requires treatment with drugs interacting with IFN alpha2a, RBV or PTX
* Patients that fail to adhere to treatment

Primary outcomes:
measure: sustained virologic rate 24 weeks post treatment with IFNalpha 2a/RBV/PTX with genotype 1 chronic HCV infection + HIV infection
timeFrame: SVR rate at 24 weeks after the end of therapy
Secondary outcomes:
measure: grade of hepatic fibrosis
timeFrame: Baseline and week 72 (for quick responders) or week 96 (for non-quick responders)
measure: rapid virologic response (RVR) and extended rapid virologic response (eRVR) rates
timeFrame: RVR at week 4 and eRVR at week 48 post treatment
Other outcomes:
measure: Percentage of patients with CC genotype on the IL28B rs12979860 polymorphism
timeFrame: week 72
Locations:
city: Guadalajara
country: Mexico
facility: Hospital Civil de Guadalajara
state: Jalisco
Study officials:
References: