Study of Darunavir/r + Tenofovir/Emtricitabine vs. Darunavir/r + Raltegravir in HIV-infected Antiretroviral naïve Subjects

Study Overview
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Brief Summary
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The triple therapy darunavir/r + tenofovir/emtricitabine is likely to become a relevant first-line treatment option in the years to come. The dual combination of boosted darunavir + raltegravir is an innovative treatment option that combines two potent new antiretroviral drugs, one of which belongs to a new drug class (integrase inhibitor). The expected efficacy profile of this combination is promising. Moreover, this combination might have a better tolerance profile and has the advantage of sparing the NRTI class. In the context of tenofovir/emtricitabine currently being a reference backbone in first-line antiretroviral regimens, we hypothesise that, in combination with darunavir/r, raltegravir may be an alternative option if its efficacy is non-inferior to tenofovir/emtricitabine.

Official Title
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An Open-label Randomised Two-year Trial Comparing Two First-line Regimens in HIV-infected Antiretroviral naïve Subjects: Darunavir/r + Tenofovir/Emtricitabine vs. Darunavir/r + Raltegravir (ANRS 143/NEAT 001)

Conditions
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HIV Infections

Intervention / Treatment
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* Drug: darunavir/ritonavir QD + raltegravir BID
* Drug: darunavir/r QD + tenofovir/emtricitabine QD (fixed dose combination)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patient with confirmed HIV infection Age ≥ 18 years Written informed consent Male patient or non-pregnant, non-lactating female No previous treatment with any antiretroviral drugs HIV-1 RNA > 1000 copies/ml Indication to start an antiretroviral treatment as long as subject has also a CD4 cell count ≤ 500/mm3 either at screening or on a sample taken within 3 months before screening No major IAS-USA mutations on genotypic testing at the screening visit or on any historical genotype, if available Non-inclusion Criteria: Woman without effective contraception method (recommended contraception during the trial is mechanical + a second method other than an oral contraceptive) Pregnant or breastfeeding woman Woman expecting to conceive during the study HIV-2 co-infection Creatinine clearance < 60 ml/mn (Cockcroft & Gault equation), alkaline phosphatase, ASAT, or ALAT ≥ 5 ULN Patient with significant impairment of hepatic function, defined as serum albumin < 2.8 g/dl or INR > 1.7 or presence of ascites, in the absence of another explanation for the abnormal finding CD4 > 500/mm3 at screening, except in case of symptomatic HIV disease (defined by conditions qualifying for CDC category B or C) or CD4 ≤ 500/mm3 on a sample taken within 3 months before screening. Any major IAS-USA mutation conferring resistance to one or more of reverse transcriptase or protease inhibitors on genotypic testing at screening Mycobacteriosis under treatment Malignancy requiring chemotherapy or radiotherapy Positive HBs Ag HCV infection for which specific treatment is ongoing or planned during the first year on trial treatment Known hypersensitivity to one of the trial drugs or its excipients Contraindicated concomitant treatment Anticipated non-compliance with the protocol Participation in another clinical trial with an on-going exclusion period at screening Subject under legal guardianship or incapacitation Subject, who in the opinion of the investigator, is unable to complete the study period

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 |
| --- | --- |
| Active Comparator: darunavir/r + tenofovir/emtricitabine<br> | Drug: darunavir/r QD + tenofovir/emtricitabine QD (fixed dose combination)<br>* darunavir 800 mg, i.e. 2 tablets of 400 mg once daily (QD) ritonavir 100 mg, 1 tablet once daily (QD) tenofovir/emtricitabine 245/200 mg, fixed dose combination, 1 tablet once daily (QD)<br>|
| Experimental: darunavir/r + raltegravir<br> | Drug: darunavir/ritonavir QD + raltegravir BID<br>* darunavir 800 mg, i.e. 2 tablets of 400 mg once daily (QD) ritonavir 100 mg, 1 tablet once daily (QD) raltegravir 400 mg, 1 tablet twice daily (BID)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to virologic or clinical failure, as the first occurrence of one of six protocol-defined components |  | minimum 2 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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HIV-infected antiretroviral naïve subjects