Safety Study of Raltegravir in HIV/HCV Co-infected Patients

Study Overview
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Brief Summary
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Current European AIDS Clinical Society (EACS) guidelines for the treatment of HIV infection recommend a combination antiretroviral regimen composed of two nucleoside reverse transcriptase inhibitors plus a ritonavir boosted protease inhibitor or a non-nucleoside reverse transcriptase inhibitor. The non-nucleoside reverse transcriptase inhibitors licensed for naïve patients - nevirapine and efavirenz - have both been asociated with increased rates of hepatotoxicity (nevirapine) and CNS toxicity (efavirenz) in HIV/HCV co-infected patients. Although PI-based therapy has dramatically reduced morbidity and mortality, it has been limited by complex dosing regimens and toxicities, leading to adherence challenges. Varying degree of liver insufficiency may necessitate pharmacokinetic monitoring of the protease inhibitor and may necessitate dose adjustments. In HIV/HCV co-infected patients HAART based on another class of antiretrovirals than NNRTI or PI may thus offer advantages with regard to adverse events and thus long-term efficacy. The overall intention of this trial is to examine in a non-inferiority design the safety and efficacy of a raltegravir based HAART with a standard-of-care HAART in HIV-/HCV co-infected patients. The standard of care used in this study will be atazanavir/ritonavir. All patients will in addition receive a fixed combination of tenofovir and emtricitabine. The primary end-point is the rate of hepatotoxic events, defined by ALT elevations.

Official Title
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An Open, Prospective Study to Compare the Safety and Efficacy of Raltegravir vs. Atazanavir / Ritonavir, Both in Combination With Tenofovir DF and Emtricitabine, in the Treatment of HIV-infection in ART Naive Subjects With HCV Co-infection.

Conditions
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HIV, Hepatitis C

Intervention / Treatment
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* Drug: raltegravir
* Drug: Atazanavir/ritonavir


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: HIV and Hepatitis C co-infected patients indication for HAART according to current German-Austrian guidelines HAART naive no primary NRTI / Integrase / PI associated resistance mutation according to the Stanford algorithm at screening; every patient MUST have a genotypic resistance assay prior baseline available (< 6 months prior to baseline) women of childbearing age: negative pregnancy test ability to sign written informed consent Exclusion Criteria: advanced liver cirrhosis Child-Pugh B or C or decompensated liver disease Pegylated interferon / ribavirin or other anti-HCV therapy; planned anti-HCV therapy for duration of the study (48 weeks). acute or chronic hepatitis B infection acute hepatitis A or other hepatotropic virus infections any other chronic liver disease such as alcohol abuse or hemosiderosis use or planned use (for the duration of the study, 48 weeks) of rifampicin, St. John´s wort and drugs that are metabolized via the cytochrome P450 system with a narrow therapeutic PK-range such as astemizole, terfenadine, cisapride, pimozide, chinidin, bepridil, triazolam, midazolam, ergotamine, dihydroergotamin, ergometrine, methyl-ergometrine. FOR OTHER COMEDICATIONS please consult with the SPC of Raltegravir (Isentress®), Atazanavir (Reyataz®), Ritonavir (Norvir®), your hospital pharmacist, www.hiv-drug-interactions.org or the principal investigator in case of uncertainty. new AIDS defining event, except for Kaposi sarcoma, < 1 months prior to screening malignancy, except for Kaposi sarcoma, with current radio- or chemotherapy history of organ transplantation

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Raltegravir<br>45 patients will receive open label raltegravir, in addition to the common backbone tenofovir and emtricitabine | Drug: raltegravir<br>* Patients will be randomized 1:1 to either the experimental or the active control arm<br>|
| Active Comparator: Atazanavir/ritonavir<br>45 patients will receive open label atazanavir/ritonavir | Drug: Atazanavir/ritonavir<br>* Patients will be randomized 1:1 to either the experimental or the active control arm<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Primary objective | there is no difference in the rate of grade 1/2, or 3/4 ALT elevations there is a higher incidence of grade 1 - 4 hyperbilirubinemias in the ATV/r arm |  | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Secondary objectives | Other parameters of safety and efficacy will be compared between both arms |  |