Simplification to Atazanavir/Ritonavir + Lamivudine as Maintenance Therapy

Study Overview
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Brief Summary
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A switch to a regimen consisting of ATV/RTV 300/100 mg QD + 3TC 300 mg QD in HIV-1 infected subjects in their first antiretroviral regimen and who are virologically suppressed on a regimen which consists of 2 NRTIs + any 3rd agent, is non-inferior to continue or switch to ATV/RTV 300/100 mg QD + 2 optimized NRTIs for maintenance of virological suppression.

Detailed Description
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Clinical Trial, phase IV, randomized, open label, multicenter with approved drugs in their use conditions. A switch to a regimen consisting of ATV/RTV 300/100 mg QD + 3TC 300 mg QD in HIV-1 infected subjects in their first antiretroviral regimen and who are virologically suppressed on a regimen which consists of 2 NRTIs + any 3rd agent, is non-inferior to continue or switch to ATV/RTV 300/100 mg QD + 2 optimized NRTIs for maintenance of virological suppression.

Official Title
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Efficacy of Simplification to Atazanavir/Ritonavir + Lamivudine as Maintenance Therapy in Patients With Viral Suppression. Randomized, Open-label 96 Weeks Non-inferiority Trial

Conditions
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HIV Infection

Intervention / Treatment
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* Drug: Ritonavir boosted Atazanavir + Lamivudine
* Drug: Ritonavir boosted Atazanavir + 2 NRTIs


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Signature of informed consent At least 18 years old Patients on their 1st ARV treatment consisting on 2 NRTIs + 1 third agent for at least 1 year Undetectable viral load for at least 6 months prior to inclusion in the study (VL<50 c/mL in 2 determinations 6 months apart; blips are not allowed). Requirement of ARV treatment change due to toxicity, intolerance or simplification. Clinically stable. Exclusion Criteria: Pregnant women or women who plan to get pregnant during the study. Breast feeding History of change of any ARV treatment component for any reason 4 months prior to the inclusion in the trial History of ARV treatment change due to virological failure History of confirmed virological failure defined as one single VL >400 c/mL or at least 2 VL between 50 and 400 c/mL one year after an indetectable VL was achieved. Absence of HIV genotype prior to ARV treatment initiation. Resistance mutation to any of the study drugs (ATV, RTV, 3TC) HBV infection. History of toxicity or intolerance to ATV, RTV or 3TC. Gilbert's syndrome. Use of contraindicated drugs. Lab abnormalities grade 4.

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: ATV/r+3TC<br>Subjects will receive ATV/RTV 300/100 mg QD + 2 optimized NRTIs for the first 4 weeks and then they will receive ATV/RTV 300/100 mg QD (once daily) and 3TC 300 mg QD for another 92 weeks. Treatment should be taken orally with a light meal at the same time each day. | Drug: Ritonavir boosted Atazanavir + Lamivudine<br>* ATV/RTV 300/100 mg QD + 2 optimized NRTIs for the first 4 weeks and then they will receive ATV/RTV 300/100 mg QD (once daily) and 3TC 300 mg QD for another 92 weeks. Treatment should be taken orally with a light meal at the same time each day.<br>|
| Active Comparator: ATV/r+2 NRTIs<br>Subjects will receive ATV/RTV 300/100 mg QD + 2 optimized NRTIs for 96 weeks. Treatment should be taken orally with a light meal at the same time each day. | Drug: Ritonavir boosted Atazanavir + 2 NRTIs<br>* ATV/RTV 300/100 mg QD + 2 optimized NRTIs for 96 weeks. Treatment should be taken orally with a light meal at the same time each day.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To assess the non-inferiority of maintenance therapy with ATV/RTV + 3TC vs ATV/RTV + 2 optimized NRTIs | Non-inferiority will be considered when the difference in proportion of efficacy between experimental arm (ATV/RTV + 3TC) vs. control arm (ATV/RTV + 2 optimized NRTIs) arm is less or equal to -0.12% after 48 weeks of treatment | Week 48 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To assess the non-inferiority of maintenance therapy with ATV/RTV + 3TC vs ATV/RTV + 2 optimized NRTIs | Non-inferiority will be considered when the difference in proportion of efficacy between experimental arm (ATV/RTV + 3TC) vs. control arm (ATV/RTV + 2 optimized NRTIs) arm is less or equal to -0.12% after 24 weeks of treatment | week 24 | 
| To assess the non-inferiority of maintenance therapy with ATV/RTV + 3TC vs ATV/RTV + 2 optimized NRTIs | Non-inferiority will be considered when the difference in proportion of efficacy between experimental arm (ATV/RTV + 3TC) vs. control arm (ATV/RTV + 2 optimized NRTIs) arm is less or equal to -0.12% after 96 weeks of treatment | week 96 | 
| To assess safety after 24 weeks fo treatment | Frequency of adverse events, SAEs, AEs leading to discontinuations, death and laboratory abnormalities. Describe renal function, plasma Vitamin D and bone density changes (DEXA) from baseline and particularly in those patients receiving TDF at screening. | Week 24 | 
| To assess safety after 48 weeks fo treatment | Frequency of adverse events, SAEs, AEs leading to discontinuations, death and laboratory abnormalities. Describe renal function, plasma Vitamin D and bone density changes (DEXA) from baseline and particularly in those patients receiving TDF at screening. | Week 48 | 
| To assess safety after 96 weeks fo treatment | Frequency of adverse events, SAEs, AEs leading to discontinuations, death and laboratory abnormalities. Describe renal function, plasma Vitamin D and bone density changes (DEXA) from baseline and particularly in those patients receiving TDF at screening. | Week 96 | 
| To assess the incidence of resistance, and characterization of this resistance following a virological rebound | Genotypic antiretroviral resistance profiles of subjects experiencing virologic failure (genotype) Plasma samples at Baseline and at each visit will be stored for additional resistance studies (i.e. cDNA) | Week 96 | 
| To assess neurocognitive function evolution | Nerocognitive function evolution measured through a battery of standardized tests from baseline to week 48 | Week 48 | 
| To assess neurocognitive function evolution | Nerocognitive function evolution measured through a battery of standardized tests from baseline to week 96 | Week 96 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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HIV, AIDS, Atazanavir, Simplification