Raltegravir One Thousand Two Hundred vs Darunavir-cb in Immnunosupressed Patients: ROTDIP Study

Study Overview
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Brief Summary
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Multicenter, randomized, open label pilot clinical trial with two parallel arms aimed to compare the efficacy of Raltegravir (RAL) 1200mg QD vs Darunavir/Cobicistat (DRV-cb) 800-150mg QD both in combination with alafenamide/emtricitabine (TAF/FTC) in patients with Human Inmunodefficiency Virus (HIV) infection and CD4<200 cells/microL

Detailed Description
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The trial consists of two parallel arms to study the therapeutic success of 48 weeks, tolerability, immunological recovery, persistence of treatment, safety and results reported by the subject in severely immunocompromised HIV infected patients (with an initial CD4 count <200 cells/μl) naive to antiretroviral therapy. Included subjects will be randomized two to one (2:1) to RAL 1200mg QD plus FTC/TAF or DRV/cb (800-150mg) plus FTC/TAF.

Official Title
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Multicenter, Open, Pilot Clinical Trial Aimed to Compare the Efficacy of RAL1200 QD vs DRV-cb 800-150 QD Both in Combination With TAF/FTC in Patients With HIV Infection and CD4 Count Under 200 Cells/microL

Conditions
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HIV Infections

Intervention / Treatment
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* Drug: Experimental: RAL QD
* Drug: Active comparator: DRV/cb


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subjects ≥ 18 years of age. HIV-1 infection. Naive to antiretroviral treatment. CD4 count at the beginning of the study <200 cells/μl. Estimated glomerular filtration ≥ 50 mL / min, according to the formula CKD-EPI. Grant Informed Consent in writing to participate in the study Exclusion Criteria: Breastfeeding, pregnant or women in childbearing age who do not commit to maintain barrier contraceptive measures during the trial. Concomitant use of any drug with possible pharmacological interaction with the study drugs that it is advisable to avoid through the database for interactions at the University of Liverpool (www.hiv-druginteractions.org). Previous use of any antiretroviral for HIV infection. Resistance to the study drugs, or presence of any contraindication to use it. The inclusion in the study can be carried out before receiving the result of the resistance test. Once it is received, in case of presenting any mutation of resistance to drugs of the indicated regimen, the patient will be removed from the study and will be offered the best available treatment for their medical condition at that time. Therapies that include interferon, interleukin-2, cytotoxic chemotherapy or immunosuppressants at the entrance to the study. Current consumption of alcohol or other substances that at the discretion of the investigator may interfere with subject's treatment compliance. Subjects who currently participate in any other clinical trial using a research product, with the exception of studies in which the treatment studied has been stopped for more than 12 weeks. AIDS event in diagnosis of HIV infection or in the 3 months prior to the inclusion of the study. Suspected severe hepatopathy (grades B or C of the Child-Pugh classification), of any origin, according to the clinician. Any other clinical condition or previous treatment that, in the investigator's judgment, makes the subject unsuitable for the study or unable to comply with the dosage requirements.

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: RAL 1200 QD<br>Start treatment with Raltegravir (RAL) 1200mg QD plus tenofovir alafenamide/emtricitabine (FTC/TAF) | Drug: Experimental: RAL QD<br>* Prescription of 2x RAL 600mg (1200MG) once daily<br>* Other names: Raltegravir (RAL) 600mg Oral Tablet;|
| Active Comparator: DRV/cb<br>Start treatment with Darunavir/Cobicistat (DRV/cb) 800-150mg QD plus tenofovir alafenamide/emtricitabine (FTC/TAF) | Drug: Active comparator: DRV/cb<br>* Prescription of DARUNAVIR/COBICISTAT 800 Mg-150 Mg once daily<br>* Other names: DARUNAVIR/COBICISTAT 800 Mg-150 Mg Oral Tablet;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Compare efficacy of RAL 1200 mg QD versus DRV/cb 800-150 mg QD, both in combination with TAF/FTC | Number of patients that will improve when having raltegravir vs darunavir | 48 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Virological failure | Number of patients in virological failure at week 48. | 48 weeks | 
| Compare the proportion of patients who interrupt the treatment for any reason | Number of patients that interrupt the treatment for any reason after 48 weeks. | 48 weeks | 
| Analyze change (percentage) in the number of CD4 lymphocytes | Percentage of change in the number of CD4 lymphocytes after 48 weeks. | 48 weeks | 
| Compare the proportion of patients with CD4>200 cells/μL at end of intervention | Compare the proportion of patients with CD4>200 cells/μL at end of intervention. | 48 weeks | 
| Percentage change in total cholesterol (TC) | Percentage of patients with change in total cholesterol (TC), | 48 weeks | 
| Percentage change in LDL and HDL cholesterol | Percentage of patients with change in LDL and HDL cholesterol | 48 weeks | 
| Percentage change in triglycerides | Percentage of patients with change the percentage change in triglycerides after 48 weeks | 48 weeks | 
| Percentage change in TC/HDL ratio | Percentage of patients with change in TC/HDL ratio | 48 weeks | 
| Change in Cardiovascular Risk 10-year predictive value (REGICOR). | Percentage of patients with change in Cardiovascular Risk 10-year predictive value (REGICOR). | 48 weeks | 
| Check GF modification using Chronic Kidney Disease Epidemiology (CKD-EPI) equation | Number of patiens with changes in glomerular filtration using Chronic Kidney Disease Epidemiology (CKD-EPI) equation. | 48 weeks |