Darunavir Levels, Virological Efficacy, Proviral ADN and Resistances in Patients on Darunavir/Ritonavir Monotherapy

Study Overview
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Brief Summary
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To evaluate the relationship between plasma and intracellular darunavir (DRV) concentrations and virological efficacy in HIV-infected patients on DRV/rtv monotherapy.

Detailed Description
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To be enrolled, subjects had a plasma HIV-RNA <50 copies/mL for at least 6 months based, virologic failure while on a PI-containing regimen was allowed if the genotypic resistance tests showed no major resistance mutation associated to reduced susceptibility to DRV/rtv according to the International AIDS Society. Patients with transitory episodes of detectable plasma HIV-RNA viral load (blip) preceded and followed by a plasma viral load <50 copies/mL without changes in antiretroviral treatment could also been included. The only exclusion criteria were pregnancy, hepatitis B coinfection and the concomitant use of drugs with potential major interactions with DRV/rtv pharmacokinetics.

Official Title
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Relation Between Darunavir Levels and Virological Efficacy, Integrated Proviral ADN and Resistance Mutations in HIV-infected Patients on Treatment With Darunavir/Ritonavir Monotherapy

Conditions
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HIV-infection

Intervention / Treatment
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* Drug: Darunavir/ritonavir


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Older than 18 years, starting an antiretroviral regimen based on darunavir-ritonavir (800/100 mg) once daily monotherapy between June 2010 and September 2010 Plasma RNA-VIH < 50 copies/ml on stable antiretroviral treatment for ≥ 6 months Absence of resistance mutations in the protease gene, based on treatment history and/or genotypic resistance testing. that would decrease darunavir susceptibility Exclusion Criteria: Pregnancy Chronic B hepatitis Genotypic resistance tests with evidence of resistance mutations in the protease gene that would decrease darunavir susceptibility Concomitant use of drugs with potentially adverse interactions with darunavir-ritonavir pharmacokinetics, such as rifampin

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 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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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Darunavir-ritonavir monotherapy<br>HIV-infected patients with undetectable viral load for at least for 6 months on stable therapy and no darunavir related mutations in the HIV-protease gene | Drug: Darunavir/ritonavir<br>* Darunavir/ritonavir (800/100 mg once daily) monotherapy<br>* Other names: Prezista/norvir;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Virological efficacy | To correlate the plasma and intracellular (cell-associated)) DRV levels with the virological efficacy analyzed by the time to loss of virological response (TLOVR) algorithm, considering VF as either: 1) two consecutive viral load >200 copies/mL, 2) a unique HIV-RNA >200 copies/mL if followed by lost to follow-up, or 3) the reintroduction of nucleos(t)ides because any reason. | 48 and 96 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Impact of viral breakthrough on DNA-HIV reservoirs and immunologic activation | Impact of blips and persistent viraemia on DNA-HIV reservoirs and immunologic activation | 48 and 96 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Antiretroviral therapy, Boosted-Darunavir monotherapy, Resistance, Proviral DNA-HIV