Study With Dual Therapy Including Lamivudine (300 mg QD) Plus Raltegravir (1200 mg QD) in Virologically Suppressed HIV-1 Infected Patients Experiencing Inconvenience, Toxicity, Negative Impact on Co-morbidities or Risk of Drug-drug Interactions With Their Current Regimen

Study Overview
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Brief Summary
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Phase 3b, single arm, simplification study with dual therapy including Lamivudine (300 mg QD) plus Raltegravir (1200 mg QD) in virologically suppressed HIV-1 infected patients experiencing inconvenience, toxicity, negative impact on comorbidities or risk of drug-drug interactions with their current regimen.

Official Title
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Phase 3b, Single Arm, Simplification Study With Dual Therapy Including Lamivudine (300 mg QD) Plus Raltegravir (1200 mg QD) in Virologically Suppressed HIV-1 Infected Patients Experiencing Inconvenience, Toxicity, Negative Impact on Co-morbidities or Risk of Drug-drug Interactions With Their Current Regimen. RALAM-II Study

Conditions
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HIV Seropositivity, HIV Infections, HIV-1-infection

Intervention / Treatment
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* Drug: Raltegravir
* Drug: Lamivudine


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 experiencing inconvenience, toxicity, negative impact on comorbidities or risk of drug-drug interactions with their current regimen Patients virologically suppressed during at least 12 months prior to inclusion (viral load <50 copies/mL). 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 Lamivudine or Emtricitabine-containing regimen. Resistance mutations to Lamivudine 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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Raltegravir + Lamivudine<br> | Drug: Raltegravir<br>* Raltegravir (1200 mg once a day)<br>Drug: Lamivudine<br>* Lamivudine (300 mg once a day)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Therapeutic failure | therapeutic failure at week 48, includes virological failure, change in treatment for any reason, consent withdrawal, loss to follow-up or death | 48 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from baseline in the reason of change of the antiretroviral treatment in those patients the reason of change was inconenience | Changes in quality of life calculated by EQ-5D-5L if reason of switch was inconvenience | 48 weeks | 
| Change from baseline in the reason of change of the antiretroviral treatment in those patients the reason of change was neurological toxicity | Changes on Pittsburgh Sleep Quality Index for neurological toxicity | 48 weeks | 
| Change from baseline in the reason of change of the antiretroviral treatment in those patients the reason of change was cardiovascular toxicity or co-morbidity | Changes on plasma lipids cholesterol LDL | 48 weeks | 
| Change from baseline in the reason of change of the antiretroviral treatment in those patients the reason of change was cardiovascular toxicity or co-morbidity | Changes on plasma lipids cholesterol HDL | 48 weeks | 
| Change from baseline in the reason of change of the antiretroviral treatment in those patients the reason of change was cardiovascular toxicity or co-morbidity | Changes on plasma lipids triglycerides | 48 weeks | 
| Change from baseline in the reason of change of the antiretroviral treatment in those patients the reason of change was skeletal toxicity | Changes on dual energy x-ray absorptiometry bone density | 48 weeks | 
| Change from baseline in the reason of change of the antiretroviral treatment in those patients the reason of change was digestive toxicity | Apperance of any adverse event that resolve their digestive toxicity: as diarrhea or digestive discomfort | 48 weeks | 
| Change from baseline in the reason of change of the antiretroviral treatment in those patients the reason of change was drug-drug interactions | Proportion of drug-drug interaction with antirretroviral treatment | 48 weeks | 
| Therapeutic failure |  | 24 weeks | 
| Virological failure | Defined as two consecutive measurements of plasma viral load above 50 copies/ml | 24 weeks | 
| Virological failure | Defined as two consecutive measurements of plasma viral load above 50 copies/ml | 48 weeks | 
| Proportion of patients with viral load below ultrasensitive HIV-1 RNA detection limit (limit of detection 1 copy/mL) |  | 48 weeks | 
| Changes from baseline in cholesterol total |  | 24 weeks | 
| Changes from baseline in HDL |  | 24 weeks | 
| Changes from baseline in triglycerides |  | 24 weeks | 
| Changes from baseline in insulin resistance (HOMA-IR) |  | 24 weeks | 
| Changes from baseline in cholesterol LDL |  | 24 weeks | 
| Changes from baseline in cholesterol LDL |  | 48 weeks | 
| Changes from baseline in cholesterol total |  | 48 weeks | 
| Changes from baseline in cholesterol HDL |  | 48 weeks | 
| Changes from baseline in triglycerides |  | 48 weeks | 
| Changes from baseline in and insulin resistance (HOMA-IR) |  | 48 weeks | 
| Changes from baseline in body fat composition |  | 48 weeks | 
| Changes from baseline in immune activation markers including CD38 |  | 48 weeks | 
| Changes from baseline in immune activation markers including HLA-DR |  | 48 weeks | 
| Changes from baseline in biomarkers of inflammation IL-6, |  | 48 weeks | 
| Changes from baseline in biomarkers of inflammation high sensitivity C-reactive protein |  | 48 weeks | 
| Changes from baseline in biomarkers of mononuclear activation SD-14 |  | 48 weeks | 
| Changes from baseline in biomarkers of mononuclear activation SD-163 |  | 48 weeks | 
| Changes from baseline in sleep quality (Pittsburgh Sleep Quality Index) |  | 24 weeks | 
| Changes from baseline in sleep quality (Pittsburgh Sleep Quality Index) |  | 48 weeks | 
| Change from baseline in EQ-5D-5L |  | 24 weeks | 
| Change from baseline in EQ-5D-5L |  | 48 weeks | 
| Incidence of adverse events |  | 48 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Lamivudine, Raltegravir