The First Failure Study

Study Overview
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Brief Summary
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The purpose of this study is to look at two different antiretroviral treatment options in individuals who are about to commence their second antiretroviral treatment. This study will assess important clinical and laboratory differences between these two therapeutic options. Potential differences include: differences in body fat distribution, in lipid parameters, in adherence and in neurocognitive (brain) function. This study is looking to show differences in body fat distribution between the two study treatment arms. Differences in lipids, viral load, adherence, cardiac and bone biomarkers and neurocognitive function will also be assessed. There is also a lumbar puncture sub study participants can also take part in. The total duration of involvement in the trial will be up to 96 weeks (approximately 2 years) plus a screening visit 1 - 4 weeks prior to the start of the study. Including visit the clinic on 12 occasions (screening visit, baseline visit, weeks 2, 4, 8, 12, 24, 36, 48, 64, 80 and 96)

Official Title
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A Randomised, Open Label, Prospective Study to Assess Two Different Therapeutic Strategies Following First Treatment Failure in HIV-1 Infected Subjects

Conditions
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HIV, HIV Infections

Intervention / Treatment
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* Drug: Darunavir, Ritonavir, Truvada
* Drug: Darunavir, Ritonavir and Etravirine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: HIV-1 infected males or females over 18 years of age signed informed consent currently receiving a stable antiretroviral regimen comprising of: two or more licensed NRTIs one licensed NNRTI or boosted protease inhibitor no previous protease inhibitor resistance documented on HIV-1 genotypic resistance testing failure of current antiretroviral regimen due to: toxicity, intolerance or virological failure if receiving an NNRTI containing regimen at screening toxicity or intolerance if receiving a boosted-protease inhibitor regimen at screening (with plasma HIV RNA < 400 copies/mL at screening) willing to modify antiretroviral therapy, in accordance with the randomisation assignment no previous exposure to etravirine subjects in good health upon medical history, physical exam, and laboratory testing in the opinion of the investigator have no serologic evidence of active HBV infection evidenced by negative hepatitis B surface antigen female subjects who are heterosexually active and of childbearing potential (i.e., not surgically sterile or at least two years post menopausal) must practice contraception as follows from screening through completion of the study: barrier contraceptives (condom, diaphragm with spermicide) IUD or Depo PLUS a barrier contraceptive female subjects of childbearing potential must have a negative pregnancy test. Exclusion Criteria: current alcohol abuse or drug dependence pregnancy active opportunistic infection or significant co-morbidities current prohibited concomitant medication a likelihood of diminished response to any of the study treatment arms, in the opinion of the investigator, based on HIV genotypic resistance testing

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 |
| --- | --- |
| Active Comparator: Standard of care<br> | Drug: Darunavir, Ritonavir, Truvada<br>* Darunavir 800 mg daily Ritonavir 100 mg daily Tenofovir 245 mg daily Emtricitabine 200 mg daily<br>* Other names: Truvada;|
| Experimental: NRTI sparing arm<br> | Drug: Darunavir, Ritonavir and Etravirine<br>* Darunavir 800 mg daily Ritonavir 100 mg daily Etravirine 400 mg once daily<br>* Other names: Intelence;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean change from baseline in peripheral and central adipose tissue | As measured by DEXA, between treatment arms. | week 48 and 96 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of patients <50 copies HIV-1 RNA/mL | At all study points to weeks 48 and 96 between treatment arms. | 96 weeks | 
| Mean change from baseline of absolute CD4+ T cell count | between treatment arms | 96 weeks | 
| Time to change in randomly assigned therapy | between treatment arms | 96 weeks | 
| Mean change from baseline Lipodystrophy Case Definition score | Between treatment arms | 96 weeks | 
| Mean change from baseline in fasting lipid and glycaemia parameters | between treatment arms | 96 weeks | 
| Mean change from baseline in cardiac and bone biomarker levels | between treatment arms | Week 96 | 
| • Comparison of total number of patients with any serious adverse events (SAEs), and the cumulative incidence of SAEs | Between the treatment arms | 96 week s | 
| Patterns of genotypic HIV resistance associated with virological treatment failure | Across the treatment arms | 96 weeks | 
| Describe aspects of immune reconstitution disease (IRD) | Across the treatment arms | 96 weeks | 
| Comparison of quality of life and results of adherence questionnaires | Between the treatment arms | 96 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Treatment experienced