Comparing Continuing Tenofovir, Emtricitabine (or Lamivudine) Plus Lopinavir and Switching to Raltegravir Plus Darunavir

Study Overview
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Brief Summary
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The main objective of this clinical trial in randomizing HIV infected patients under good HIV control with tenofovir (TDF), emtricitabine (or lamivudine) plus lopinavir/ritonavir (LPV/r) into switching the regimen to raltegravir (RAL) with darunavir/ritonavir (DRV/r) or continuing the ongoing regimen to compare these two groups' estimated glomerular filtration rate (eGFR) is to investigate whether anti-HIV treatment that does not contain TDF or other reverse-transcriptase inhibitors (NTRI sparing regimen) can be protective of patients' renal functions and has the same virological efficacy in comparison with a standard treatment with TDF, or not.

Detailed Description
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Eligibility criteria are HIV infected outpatients or inpatients that are: without history virological failure including protease inhibitors or raltegravir (disregarding whether the patient had a history of drug resistance or drug holiday, or not) taking LPV/r+TVD (or TDF+lamivudine) for longer than 15 weeks before the enrollment with HIV viral load less than 50 copies/ml for 15 weeks, including those with blips (one time episode of detectable level HIV viraemia which are proceeded and followed by undetectable viraemia). 20 years old or older Japanese willing to participate in the trial and able to agree to the informed consent. Main outcome measures are to investigate if the estimated glomerular filtration rate (eGFR) of the intervened group with RAL+DRV/r improves by 10% or more by intention to treat (ITT) analysis at the time of 48 weeks after the start of the trial. Other outcome measures are: virological efficacy of the group on DRV/r+RAL (after 48 weeks and up to 96 weeks) comparison of other renal function markers between the two arms: serum creatinine, urine beta-2 microglobulin, tubular resorption rate of phosphate, urine albumin, N-acetyl-beta-glucosaminidase, serum cystatin C, urine protein and urine glucose (after 48 weeks and up to 96 weeks) comparison of lipid markers between the two arms: triglycerides, HDL cholesterol, LDL cholesterol and total cholesterol (after 48 weeks and up to 96 weeks) discontinuation rate of each arm, reason and timing of the discontinuation or the treatment change up to 96 weeks adverse events of each arm, symptoms and rate up to 96 weeks blood plasma concentration level of RAL and DRV of all consented intervened cases at National Center for Global Health and Medicine

Official Title
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Switching From Lopinavir/Ritonavir Plus Tenofovir and Emtricitabine (or Lamivudine) to Darunavir (Prezista) and Raltegravir to Evaluate Renal Function

Conditions
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HIV Infections

Intervention / Treatment
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* Drug: Raltegravir, Darunavir/r


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: HIV infected outpatients or inpatients that are without history virological failure including protease inhibitors or raltegravir (disregarding whether the patient had a history of drug resistance or drug holiday, or not) taking LPV/r+TVD (or TDF+lamivudine) for longer than 15 weeks before the enrollment with HIV viral load less than 50 copies/ml for 15 weeks, including those with blips (one time episode of detectable level HIV viraemia which are proceeded and followed by undetectable viraemia) 20 years old or older Japanese willing to participate in the trial and able to agree to the informed consent Exclusion Criteria: cases applicable to any of the following will be excluded from this trial HBs antigen positive within 15 weeks to the enrollment (cases confirmed as HBs antibody positive can be enrolled without HBs antigen testing) malabsorption or gastrointestinal symptoms that affect absorption of the drugs, or dysphagia cases clinical data within 15 weeks before the start of the trial and of the closest date to the enrollment that are GPT 2.5 times the highest of the normal range (grade 2) or eGFR less than 60ml/min (Cockcroft-Gault formula) cases with opportunistic infections requiring treatment (primary and secondary preventive prophylaxis can be administrated during the study) cases during pregnancy or nursing period, or with a possibility for pregnancy using drugs that are prohibited to combine for drug interaction with the drugs of this trial other cases that are decided by the patient's physician as not suitable for the trial

Ages Eligible for Study
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Minimum Age: 20 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: Raltegravir, Darunavir/r<br>An arm to change the regimen from: Kaletra 4 tabs QD and Truvada 1 tab QD or Kaletra 4 tabs QD, Viread 1 tab QD, Epivir300mg 1 tab (or Epivir 150mg 2 tabs) QD to: Prezista naive 2 tabs PC QD, Norvir soft-capsule 1 cap PC QD and Isentress 1 tab BID or Prezista 2 tabs PC BID and Norvir soft-capsule 1 cap PC BID, and Isentress 1 tab BID | Drug: Raltegravir, Darunavir/r<br>* An arm to change the regimen to: raltegravir and darunavir/ritonavir Prezista naive 2 tabs PC QD, Norvir soft-capsule 1 cap PC QD and Isentress 1 tab BID or Prezista 2 tabs PC BID and Norvir soft-capsule 1 cap PC BID, and Isentress 1 tab BID from: Kaletra 4 tabs QD and Truvada 1 tab QD or Kaletra 4 tabs QD, Viread 1 tab QD, Epivir300mg 1 tab (or Epivir 150mg 2 tabs) QD<br>* Other names: NRTI sparing regimen;|
| No Intervention: Tenofovir, Emtricitabine, Lopinavir/r<br>An arm continuing on the same regimen before the randomization as Kaletra 4 tabs QD and Truvada 1 tab QD or Kaletra 4 tabs QD, Viread 1 tab QD, Epivir300mg 1 tab (or Epivir 150mg 2 tabs) QD | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| eGFR improvement comparison of two arms by ITT analysis | To investigate whether the estimated glomerular filtration rate (eGFR) of the intervened group with RAL+DRV/r improves by 10% or more by intention to treat (ITT) analysis at the time of 48 weeks after the start of the study, or not. | 48 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Virological efficacy | Virological efficacy of the group on DRV/r+RAL | 48 weeks up to 96 weeks | 
| Renal function markers | Serum creatinine, eGFR, uine beta-2 microglobulin, tubular resorption rate of phosphate, urine albumin, N-acetyl-beta-glucosaminidase, serum cystatin C, urine protein and urine glucose | 48 weeks up to 96 weeks | 
| Lipids | Triglycerides, HDL cholesterol, LDL cholesterol and total cholesterol | 48 weeks up to 96 weeks | 
| Adverse events | Adverse events of each arm, symptoms and rate | 96 weeks | 
| Blood plasma concentration of RAL and DRV | Blood plasma concentration level of raltegravir and darunavir among all consented and intervened cases at National Center for Global Health and Medicine | 96 weeks | 
| Discontinuation rate | Discontinuation rate of each arm, reason and timing | 96 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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HIV-1, AIDS, Clinical Trials, Randomized