Study to Evaluate Darunavir/Ritonavir + Lamivudine Versus Continuing With Darunavir/Ritonavir + Tenofovir/Emtricitabine or Abacavir/Lamivudine in HIV Infected Subject

Study Overview
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Brief Summary
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This is an open label randomized clinial trial to evaluate the treatment with darunavir/ritonavir (800mg/100mg) plus lamivudine (300 mg) once daily versus continuing with darunavir/ritonavir (800mg/100mg) once daily plus tenofovir/emtricitabine (300mg/200mg) or abacavir/lamivudine (600mg/300mg) in HIV infected subject with suppressed plasma viremia.

Official Title
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An Open Label Randomized Clinical Trial, to Evaluate the Treatment With Darunavir/Ritonavir + Lamivudine Once Daily Versus Continuing With Darunavir/Ritonavir Once Daily + Tenofovir/Emtricitabine or Abacavir/Lamivudine in HIV Infected Subject With Suppressed Plasma Viremia

Conditions
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HIV Infection

Intervention / Treatment
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* Drug: Darunavir/Ritonavir
* Drug: Lamivudine
* Drug: Emtricitabine/tenofovir or abacavir/lamivudine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Acceptance to participate in the study, signing the informed consent document before conducting any study procedures. Patient with HIV infection older than 18 years. Treatment with darunavir/ritonavir once a day and tenofovir/emtricitabine or abacavir/lamivudine during at least 4 weeks at the moment of the screening Plasma HIV RNA levels below 50 copies / ml for at least 6 months (two separate measurements at least 6 months with viremia <50 copies / ml between both). HbsAg negative Exclusion Criteria: Pregnant or breastfeeding woman Evidence of Lamivudine resistance (any previous genotype with mutation M184V/I or K65R) and/or to darunavir (population genotype show any of the following mutations: V11I, V32I, L33F, I47V, I50V, I54L/M, G73S, T74P, L76V, I84V, L89V). History of virology failure (two consecutive viral loads above 200 copies/ml) while the patient was receiving a regimen with lamivudine or emtricitabine, with the following exceptions: Do not consider an exclusion criterion if the genotype performed at the time of failure does not demonstrate resistance to lamivudine and darunavir (see criteria 2). Do not consider an exclusion criteria in the absence of genotype if after the episode turns to maintain a viral load <50 copies / ml with a treatment composed of lamivudine or emtricitabine + a nucleoside + a non-nucleoside. History of abandonment of treatment including lamivudine or emtricitabine, with the following exception: - Viral load prior to abandonment was <50 copies / ml and subsequent reintroduction of the same treatment or another treatment consisting of lamivudine or emtricitabine + a nucleoside + a non-nucleoside returns to maintain viral load below 50 copies / ml . Previous treatment with bitherapy or monotherapy with lamivudine or emtricitabine Previous treatment with bitherapy or monotherapy with a regimen with a protease inhibitor that is terminated by viral rebound, when the absence of a genotypic resistance test available after viral rebound allow discard the resistance mutations either drug used. The use of concomitant medication not permitted Presence of active acute infection, including opportunist infection that a judge of investigator that can difficult the participation in the trial Any laboratory results of the following: hemoglobin<8,0 g/dl; neutrophils <750 cells/µl; platelets <50.000 cell/µl; creatinine ≥ 1,5 ULN (upper limit of normal) Any clinical or analytic event that, in the investigator judgment, condition the patient safety

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: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Darunavir/Ritonavir + 2 nucleos(t)idos<br>Darunavir/Ritonavir ( (800mg/100mg) + Tenofovir/emtricitabine (300mg/200mg) or Abacavir/lamivudine (600 mg/300mg) | Drug: Darunavir/Ritonavir<br>* Darunavir/ritonavir (800/100 mg): QD (quaque die )<br>* Other names: Prezista/Norvir;Drug: Emtricitabine/tenofovir or abacavir/lamivudine<br>* Emtricitabine/tenofovir (300/200 mg) or abacavir/lamivudine (600/300 mg): QD<br>* Other names: Truvada or Kivexa;|
| Experimental: Darunavir/ritonavir + Lamivudine<br>Darunavir/Ritonavir (800mg7100mg) + lamivudine (300mg) | Drug: Darunavir/Ritonavir<br>* Darunavir/ritonavir (800/100 mg): QD (quaque die )<br>* Other names: Prezista/Norvir;Drug: Lamivudine<br>* Lamivudine (300mg) : QD<br>* Other names: Epivir;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of patients with undetectable viral load | Undetectable viral load <50 copies/ml according to the FDA snapshot algorithm | week 48 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of patients with undetectable viral load | Undetectable viral load < 50 copies/ml according to the FDA snapshot algorithm | Week 24 | 
| Proportion of patients with viral load < 200 copies/ml | Proportion of patients with viral load < 200 copies/ml according to FDA snapshot algorithm | week 48 | 
| Proportion of patients who present viral load ≥ 50 copies /ml one time | Viral load ≥ 50 copies/ml | From basal visit until week 48 visit | 
| Proportion of patients who present viral load ≥ 50 copies /ml more tan two times | Viral load ≥ 50 copies /ml | From basal visit until week 48 visit | 
| Proportion of patients who maintained viral load < 50 copies/ml in all determinations | Viral load < 50 copies/ml | week 48 | 
| Median of change cells CD4/µl count from basal to week 48 | CD4/µl | week 48 | 
| Median of change in triglycerides , LDL-cholesterol, HDL-cholesterol and total cholesterol from basal to week 48 |  | week 48 | 
| Change in renal function | Change in glomerular filtration | week 48 | 
| Change in proportion of patients with renal tubular dysfunction |  | week 48 |