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

This study is currently recruiting participants. (see Contacts and Locations)
Verified April 2013 by Imperial College London
Sponsor:
Collaborators:
Cheif Investigator: Alan Winston
collaborators: Pfizer
Information provided by (Responsible Party):
Naomi Gardner, Imperial College London
ClinicalTrials.gov Identifier:
NCT01367236
First received: June 3, 2011
Last updated: April 3, 2013
Last verified: April 2013

June 3, 2011
April 3, 2013
January 2013
January 2015   (final data collection date for primary outcome measure)
cognitive function [ Time Frame: 48 weeks ] [ Designated as safety issue: No ]

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.

Same as current
Complete list of historical versions of study NCT01367236 on ClinicalTrials.gov Archive Site
brain function [ Time Frame: 48 weeks ] [ Designated as safety issue: No ]
The study team will assess the brain functions at each visit. Also the blood will be monitored for efficacy of treatment in the two study limbs at all visits (this is part of normal care). Likewise the results of the MRI scans will be compared. The lumbar puncture performed at the final visit will obtain samples of CSF and certain test will be performed on this to examine the differences between the two study treatments. The comparison of the scan and lumbar puncture results will indicate how the brain is differently effected with different treatments.
Same as current
Not Provided
Not Provided
 
Changes in Cerebral Function in Treatment Naive HIV-1 Infected Subjects Commencing Either Boosted Atazanavir With Truvada or Boosted Darunavir With Maraviroc and Kivexa
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.

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.

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.

Interventional
Phase 4
Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
  • HIV
  • Impaired Cognition
  • Drug: standard care
    • atazanavir 300 mg daily
    • ritonavir 100 mg daily
    • tenofovir 245 mg daily*
    • emtricitabine 200 mg daily*
  • Drug: novel treatment
    • darunavir 800 mg daily
    • ritonavir 100 mg daily
    • lamivudine 300 mg daily** and abacavir 600mgs daily**
    • maraviroc 150 mg once daily
  • Active Comparator: standard care

    treatment with:

    • atazanavir 300 mg daily
    • ritonavir 100 mg daily
    • tenofovir 245 mg daily*
    • emtricitabine 200 mg daily* * as the fixed dose combination Truvada™
    Intervention: Drug: standard care
  • Active Comparator: Novel therapeutic approach
    • 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 ™
    Intervention: Drug: novel treatment
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruiting
50
January 2015
January 2015   (final data collection date for primary outcome measure)

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
Both
18 Years and older
No
Contact: Andrew Whitehouse, MBBS 02075943413 a.whitehouse@imperial.ac.uk
Contact: Alan Winston, MD a.winston@imperial.ac.uk
United Kingdom
 
NCT01367236
1733, 2011-002656-14
Yes
Naomi Gardner, Imperial College London
Imperial College London
  • Cheif Investigator: Alan Winston
  • collaborators: Pfizer
Not Provided
Imperial College London
April 2013

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP