Changes in Cerebral Function in Treatment Naive HIV-1 Infected Subjects Commencing Either Boosted Atazanavir With Truvada or Boosted Darunavir With Maraviroc and Kivexa

Study Overview
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Brief Summary
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The purpose of this study is to compare two different combination anti-HIV therapies over 48 weeks and to assess if differences in improvement in the function of the brain are observed over this period. The study will compare anti-HIV therapy combinations which are currently in use. The patients will not have had any previous treatment for their HIV infection.

Detailed Description
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Impairment in neurocognitive(NC) function in HIV-infected subjects in the current anti-retroviraltreatment (cART) era has been associated with poor compliance with cART, reduced quality-of-life and increased mortality. Reported factors associated with the development of NC function impairment in HIV disease and risks associated with progression of such impairment include degree of immune suppression related to HIV infection, other chronic viral infections (such as chronic hepatitis C co-infection), age and central nervous system (CNS) antiretroviral drug exposure. One modifiable factor which may be associated with the evolution of NC function impairment is the direct effect of cART on the central-nervous-system (CNS). Certain antiretroviral drugs such as zidovudine, lamivudine, abacavir, nevirapine, efavirenz and indinavir are known to achieve optimal exposure in the cerebro-spinal-fluid (CSF) whereas other drugs, such as the majority of the HIV-1 protease inhibitors penetrate less effectively. Studies to date suggest different cART regimens may have differing effects on NC performance. In the EuroSIDA study, the use of nucleoside-reverse-transcriptase inhibitors was found to specifically protect against the development of HIV related brain disease. More recently, in a small prospective study, ALTAIR, different effect on cerebral function was reported in subjects randomised to commence three different cART regimens. The investigators propose, in a prospective, randomised study to assess the effects of two different antiretroviral regimens on NC function in HIV infected subjects commencing antiretroviral therapy for the first time.

Official Title
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A Randomised, Prospective Study, Assessing Changes in Cerebral Function in Treatment Naive HIV-1 Infected Subjects Commencing Either Boosted Atazanavir With Truvada or Boosted Darunavir With Maraviroc and Kivexa.

Conditions
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HIV, Impaired Cognition

Intervention / Treatment
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* Drug: standard care
* Drug: novel treatment


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: HIV-1 infected males or females signed informed consent no previous antiretroviral treatment since HIV diagnosis screening CD4+ lymphocyte count <= 350 cells/ųL susceptible to all currently licensed (Nucleoside Reverse Transcriptase Inhibitors) NRTIs, (Non-Nucleoside Reverse Transcriptase Inhibitors) NNRTIs and PIs based on HIV-1 genotypic resistance report CCR5-tropic HIV based on genotypic resistance testing* Exclusion Criteria: • existing neurological disease hepatitis B or hepatitis C co-infection age under 18 years screening laboratory parameters > grade 2 (with the exception of cholesterol and triglycerides) current history of major depression or psychosis recent head injury (past three months) current alcohol abuse or drug dependence active opportunistic infection or significant co-morbidities patients who are receiving other concomitant medication which are not permitted, as listed in appendix 2 female patients of child-bearing potential who: have a positive serum pregnancy test at screening or during the study are breast feeding are planning to become pregnant all participants unwilling to use a barrier method of contraception patients who in the opinion of the investigator are not candidates for inclusion in the study

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 care<br>treatment with: atazanavir 300 mg daily ritonavir 100 mg daily tenofovir 245 mg daily* emtricitabine 200 mg daily* * as the fixed dose combination Truvada™ | Drug: standard care<br>* atazanavir 300 mg daily ritonavir 100 mg daily tenofovir 245 mg daily* emtricitabine 200 mg daily*<br>|
| Active Comparator: Novel therapeutic approach<br>darunavir 800 mg daily ritonavir 100 mg daily lamivudine 300 mg daily** abacavir 600 mg daily** maraviroc 150 mg once daily ** as the fixed dose combination Kivexa ™ | Drug: novel treatment<br>* darunavir 800 mg daily ritonavir 100 mg daily lamivudine 300 mg daily** and abacavir 600mgs daily** maraviroc 150 mg once daily<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cognitive Function, Global Cognitive Score (Z-score) | When commencing antiretroviral therapy (anti-HIV therapy) for the first time, improvements in the function of the brain are frequently observed. For example memory and concentration may improve. However, whether these improvements may differ between different anti-HIV therapies is largely unknown. The purpose of this study is to compare two different combination anti-HIV therapies over 48 weeks and to assess if differences in improvement in the function of the brain are observed over this period. Score increase means improved performance of cognitive function | 24 weeks, 48 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Brain Function, Absolute Change Over 48 Weeks of N-acetyl Aspartate/Creatinine Ratio | The study team will assess the brain functions at each visit. The results of the MRI scans will be compared, changes in N-acetyl aspartate/creatinine ratio over 48 weeks. | 48 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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HIV