Safety & Efficacy of Dual Therapy With Raltegravir/Lamivudine

Study Overview
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Brief Summary
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A pilot 24-week open-label, randomized, controlled clinical trial to assess the safety, tolerability and efficacy of dual therapy with Raltegravir/Lamivudine combination when replacing standard combination therapy in HIV-infected patients with prolonged virological suppression

Official Title
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Pilot 24week Clinical Trial to Assess the Safety, Tolerability and Efficacy of Dual Therapy With Raltegravir/Lamivudine Combination, Replacing Standard Combination Therapy in HIV-infected Pts With Prolonged Virological Suppression.

Conditions
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AIDS

Intervention / Treatment
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* Drug: Raltegravir/3TC
* Drug: EFV/TDF/FTC
* Drug: ATV/r + TDF/FTC or DRV/r + TDF/FTC
* Drug: DTG+ABC/3TC DTG+TDF/FTC EVG/cobi/TDF/FTC RAL+TDF/FTC
* Drug: EFV plus ABC/3TC or RPV/TDF/FTC
* Drug: ATV/r plus ABC/3TC
* Drug: DRV/r + ABC/3TC or LPV/r + ABC/3TC or LPV/r + TDF/FTC
* Drug: RAL plus ABC/3TC
* Drug: Other ART regimens


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Eligible patients will be males or females at least 18 years of age. Women of childbearing potential must have a negative pregnancy test within 10 days prior to randomization into the study. Patients seropositive for HIV-1 using standard diagnostic criteria. Patients virologically suppressed during at least 12 months prior to inclusion (viral load <50 copies/mL). Patients on combination antiretroviral therapy (at least 2 antiretroviral drugs) for at least 12 months before being randomized in this study. Patients who are clinically stable in the opinion of the investigator at study entry (clinical status and chronic medication must not have not been modified at least 14 days prior to randomization). Patients who have signed informed consent to participate in the study. Exclusion Criteria: Pregnancy, lactation, or planned pregnancy during the study period. Previous failure to an integrase inhibitor-containing regimen. Previous failure to a 3TC or FTC-containing regimen. Resistance mutations to 3TC or integrase inhibitor if any resistance test had been previously performed. Any disease or history of disease which, in the opinion of the investigator, might confound the results of the study or pose additional risk to patient treatment. Chronic hepatitis B.

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: Group 1 Raltegravir / 3TC (MK0518B<br>Raltegravir / 3TC (MK0518B ) (50 patients) | Drug: Raltegravir/3TC<br>* MK0518B (Raltegravir/3TC) (300mg/150mg) twice daily, administered orally in the 300/150 mg film-coated tablets according to instructions in the prescribing information.<br>|
| Active Comparator: Group 2 standard combination therapy<br>NNRTI-Based Regimen: • EFV/TDF/FTC PI-Based Regimens: ATV/r + TDF/FTC or DRV/r + TDF/FTC INSTI-Based Regimens: DTG+ABC/3TC DTG+TDF/FTC EVG/cobi/TDF/FTC RAL+TDF/FTC NNRTI-Based Regimens: EFV plus ABC/3TC or RPV/TDF/FTC PI-Based Regimen: ATV/r plus ABC/3TC PI-Based Regimens: DRV/r + ABC/3TC or LPV/r + ABC/3TC or LPV/r + TDF/FTC INSTI-Based Regimen: RAL plus ABC/3TC And other ART regimens | Drug: EFV/TDF/FTC<br>* standard combination therapy<br>* Other names: NNRTI-Based Regimen;Drug: ATV/r + TDF/FTC or DRV/r + TDF/FTC<br> <br> * Other names: PI-Based Regimens;Drug: DTG+ABC/3TC DTG+TDF/FTC EVG/cobi/TDF/FTC RAL+TDF/FTC<br> <br> * Other names: INSTI-Based Regimens;Drug: EFV plus ABC/3TC or RPV/TDF/FTC<br> <br> * Other names: NNRTI-Based Regimens;Drug: ATV/r plus ABC/3TC<br> <br> * Other names: PI-Based Regimen;Drug: DRV/r + ABC/3TC or LPV/r + ABC/3TC or LPV/r + TDF/FTC<br> <br> * Other names: PI-Based Regimens;Drug: RAL plus ABC/3TC<br> <br> * Other names: INSTI-Based Regimen;Drug: Other ART regimens<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Efficacy in virological suppression assessed with standard plasma HIV-1 RNA detection | Efficacy in virological suppression assessed with standard plasma HIV-1 RNA detection | 24 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Efficacy in virological suppression assessed with ultrasensitive HIV-1 RNA detection (limit of detection 1 copy/mL) | efficacy in virological suppression assessed with ultrasensitive HIV-1 RNA detection (limit of detection 1 copy/mL) | 24 weeks | 
| changes in peripheral mononuclear blood cells HIV-1 reservoir |  | 24 weeks | 
| changes in insulin resistance (HOMA-IR) | Composite measure | 24 weeks | 
| changes in body fat composition | Composite measure | 24 weeks | 
| changes in plasma 25-OH vitamin D levels |  | 24 weeks | 
| changes in estimated glomerular filtration rate (CKD-EPI) | Composite measure | 24 weeks | 
| changes in CD38 |  | 24 weeks | 
| changes in IL-6 |  | 24 weeks | 
| changes in sleep quality (Pittsburgh Sleep Quality Index) |  | 24 weeks | 
| changes in adherence in both treatment arms (Morisky-Green Test)overall tolerability |  | 24 weeks | 
| Changes in total cholesterol |  | 24 weeks | 
| Changes in HDL cholesterol |  | 24 weeks | 
| Changes in LDL cholesterol |  | 24 weeks | 
| Changes in triglycerides |  | 24 weeks | 
| Changes in bone mineral density | DEXA | 24 weeks | 
| Changes in urine beta-2-microglobulin |  | 24 weeks | 
| changes in HLA-DR |  | 24 weeks | 
| Changes in high sensitivity C-reactive protein |  | 24 weeks | 
| Changes in mononuclear activation SD-14 |  | 24 weeks | 
| Changes in mononuclear activation SD-163 |  | 24 weeks |