NCT01231685

Raltegravir Switch Study to Reduce Liver Fibrosis Progression in HIV-Hepatitis C Co-infection

A Randomized Prospective Open Label Study of Switching to Raltegravir Based ART Compared to Maintaining Ritonavir Boosted PI-based ART on Liver Fibrosis Progression in HIV-HCV Coinfected Patients

• Status: Completed
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 9 (actual)
• Sponsor: McGill University Health Centre/Research Institute of the McGill University Health Centre · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

HIV infection exerts a negative impact on the course of HCV infection. Co-infected individuals progress more rapidly to liver fibrosis, cirrhosis and ESLD compared to those infected with HCV alone. Some of the this accelerated fibrosis may be related to longterm chronic toxicity from protease inhibitor based ART. Hypothesis: Switching from ritonavir boosted-PI based ART regimen to a Raltegravir-based regimen will reduce the rate of hepatic fibrosis progression in HIV-HCV co-infected patients as measured by transient elastography (Fibroscan®) and the AST-to-platelet ratio index (APRI).

Detailed description

Primary Objective-To assess if switching from ritonavir boosted-PI based ART regimen to a Raltegravir-based regimen will reduce the rate of hepatic fibrosis progression in HIV-HCV co-infected patients as measured by transient elastography (Fibroscan®) and the AST-to-platelet ratio index (APRI) after 48 weeks of treatment. Secondary Objectives: (i) To assess the safety and tolerability of switching from a ritonavir boosted-PI ART regimen to a raltegravir-based regimen for 48 weeks. (ii) To evaluate hepatic function (liver enzymes) at weeks 0, 2, 4, 8, 12, 24, 36, 48 and 72 post switch. (iii) To evaluate the effect of switching treatment on control of HIV infection (as measured by HIV viral load and CD4) at weeks 0, 4, 8, 12, 24, 36, 48, and 72 post switch. (iv) To evaluate metabolic profiles (e.g, fasting lipid profiles, glucose and insulin) at weeks 0, 24, 48 and 72 post switch. (v) To evaluate inflammatory markers associated with liver fibrosis at weeks 0, 2, 4, 8, 12, 24, 36, 48 and 72 post switch. Population: Patients will be selected from CTN222; a Canadian National multisite prospective cohort of HCV-HIV infected persons (N=978) or from other eligible patients followed at participating sites. All patients recruited into the cohort are adults aged over 16 years old with documented HIV infection (ELISA with western blot confirmation) and with chronic HCV infection or evidence of HCV exposure (e.g. HCV-seropositive by ELISA with RIBA II or EIA confirmation, or if serologically false negative, HCV RNA+). Study Design: A Randomized Prospective Open label study Sample Size: N = 40 This is a Phase II study designed to evaluate the safety and feasibility of a switch to raltegravir in HIV-HCV co-infected patients. As neither the duration of time required to improve fibrosis nor the potential impact of such a switch currently is known, this trial will provide important pilot data with which to estimate the true effect size and calculate the sample size required to conduct a larger definitive study on this question. It is hypothesized that switching therapy will lead to significant reduction in fibrosis as measured by APRI and FibroScan®. In other studies, for example, of successful HCV treatment using FibroScan®, a 34% reduction in fibrosis score was observed in those obtaining a sustained virologic response at 48 weeks (e.g., from mean baseline score of 10.3 kPa to 6.6 kPa at 48 weeks; s.d.= 5 kPa 1). We propose a sample size of 20 patients in each group, which would provide approximately 80% power to detect at least a difference of 5 kPa in fibrosis score change between the two groups assuming a similar standard deviation.

Conditions

• HIV
• Hepatitis C
• Liver Fibrosis

Interventions

Type	Name	Description
DRUG	Raltegravir	Subjects will maintain their nucleoside backbone and switch ritonavir-boosted protease inhibitor to Raltegravir 400 mg po BID for 48 weeks.
DRUG	Ritonavir-boosted protease inhibitor	Subjects will maintain their nucleoside backbone and remain on a ritonavir-boosted protease inhibitor at standard doses for for 48 weeks

Timeline

• Start date: 2011-12-01
• Primary completion: 2016-03-01
• Completion: 2016-09-01
• First posted: 2010-11-01
• Last updated: 2016-09-21

Locations

3 sites across 1 country: Canada