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)

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.

Study Overview

• Status: Completed
• Conditions: HIV; Impaired Cognition
• Intervention / Treatment: Drug: standard care; Drug: novel treatment

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 60
• Phase: Phase 4

Contacts and Locations

Study Locations

• United Kingdom
  • Birmingham, United Kingdom
    • Birmingham Heartlands Hospital:
  • Brighton, United Kingdom, BN1 9RE
    • Brighton and Sussex University Hospital NHS Trust:
  • London, United Kingdom
    • St. Thomas' Hospital
  • London, United Kingdom, SE5 9RJ
    • Kings College Hospital
  • London, United Kingdom, SW10 9NH
    • Chelsea and Westminster Hospital NHS Trust
  • London:, United Kingdom, W2 1NY
    • St. Mary's Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
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™	Drug: standard care; atazanavir 300 mg daily; ritonavir 100 mg daily; tenofovir 245 mg daily*; emtricitabine 200 mg daily*
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 ™	Drug: novel treatment; darunavir 800 mg daily; ritonavir 100 mg daily; lamivudine 300 mg daily** and abacavir 600mgs daily**; maraviroc 150 mg once daily

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Imperial College London
• Collaborators: Pfizer
• Investigators: Principal Investigator: Alan Winston, Imperial College London

Publications and helpful links

General Publications

• Mora-Peris B, Bouliotis G, Ranjababu K, Clarke A, Post FA, Nelson M, Burgess L, Tiraboschi J, Khoo S, Taylor S, Ashby D, Winston A. Changes in cerebral function parameters with maraviroc-intensified antiretroviral therapy in treatment naive HIV-positive individuals. AIDS. 2018 May 15;32(8):1007-1015. doi: 10.1097/QAD.0000000000001786.

Study record dates

Study Major Dates

• Study Start (Actual): January 1, 2013
• Primary Completion (Actual): October 1, 2015
• Study Completion (Actual): October 1, 2015

Study Registration Dates

• First Submitted: June 3, 2011
• First Submitted That Met QC Criteria: June 6, 2011
• First Posted (Estimate): June 7, 2011

Study Record Updates

• Last Update Posted (Actual): October 21, 2019
• Last Update Submitted That Met QC Criteria: October 15, 2019
• Last Verified: October 1, 2019

More Information

Terms related to this study

• Keywords: HIV
• Additional Relevant MeSH Terms: Mental Disorders; Neurocognitive Disorders; Cognition Disorders; Cognitive Dysfunction
• Other Study ID Numbers: 1733; 2011-002656-14 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No