Clinical Trial Assessing Once Daily Raltegravir Administration (800 mg QD) in HIV-1-Infected Patients Receiving Unboosted Atazanavir (400 mg QD)- Based Antiretroviral Therapy

Study Overview
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Brief Summary
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The co-administration of raltegravir with medicinal products that are knouwn to be potent UGT1A1 inhibitors, such as atazanavir, may increase plasma levels of raltegravir. So once daily raltegravir (800 mg QD), instead of twice a day (400 mg BID), could be an appropriate therapeutic option in HIV-infected patients also receiving atazanavir-containing antiretroviral regimens. In this study, pharmacokinetic data supporting this hypothesis are recovered.

Detailed Description
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Treatment adherence is crucial for the effectiveness of antiretroviral therapy, and, in an attempt to promote treatment adherence by the patients, once daily (QD) regimens are preferred rather than twice daily (BID) regimens. The dose of 400 mg BID of raltegravir has been recently licensed for the treatment of human immunodeficiency virus (HIV-1) infection in treatment-experienced adult patients. Raltegravir is eliminated mainly by metabolism via uridine diphosphate glucuronyl transferase (UGT1A1)-mediated glucuronidation pathway. Thus, co-administration of raltegravir with medicinal products that are known to be potent UGT1A1 inhibitors, such as atazanavir, may increase plasma levels of raltegravir. Based on these data, it could be hypothesized that once daily raltegravir (800 mg QD) could be an appropriate therapeutic option in HIV-infected patients also receiving atazanavir-containing antiretroviral regimens. However, pharmacokinetic data supporting this hypothesis are lacking.

Official Title
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Clinical Trial Assessing Once Daily Raltegravir Administration (800 mg QD) in HIV-1-Infected Patients Receiving Unboosted Atazanavir (400 mg QD)- Based Antiretroviral Therapy

Conditions
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HIV Infections

Intervention / Treatment
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* Drug: Addition of raltegravir 800 mg QD to HAART


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients aged 18 to 65 years old with documented HIV-1 infection. Patients on antiretroviral regimen that includes atazanavir 400mg QD for at least 4 weeks. Complete virological suppression (<50 copies/mL) for at least 12 months. Voluntary written informed consent. Ability of compliance with visit schedule. Exclusion Criteria: AIDS defining condition within 4 weeks prior to the initiation of the study. Concomitant treatment with ritonavir as well as with inducers (NNRTI, rifampin, carbamazepine, phenytoin, phenobarbital, valproic acid, etc) or inhibitors (probenecid, etc) of the uridine diphosphate glucuronyl transferase within 2 weeks before the screening visit. Concomitant therapy with tenofovir. History or suspected poor adherence to HAART. History of drug allergy to raltegravir

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1<br>Addition of raltegravir 800 mg QD to HAART | Drug: Addition of raltegravir 800 mg QD to HAART<br>* Addition of raltegravir 800 mg QD to HAART<br>* Other names: HAART+RAL;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Raltegravir area under the curve (AUC) 24 hours and Cmin |  | Day 10 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Adverse events |  | Baseline (BL), Day 10 | 
| Adherence |  | BL, Day 10 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Atazanavir, Raltegravir, once-daily, pharmacokinetics, HIV