Clinical trial NCT01367236: Changes in Cerebral Function in Treatment Naive HIV-1 Infected Subjects Commencing Either Boosted Atazanavir With Truvada or Boosted Darunavir With Maraviroc and Kivexa
Official title: 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.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: HIV
Impaired Cognition
Keywords: HIV
Lead sponsor: Imperial College London
Sponsor class: OTHER
Collaborators: name: Pfizer
First posted: 2011-06-07
Enrollment: 60
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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: 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.

Eligibility criteria: 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

Primary outcomes:
measure: Cognitive Function, Global Cognitive Score (Z-score)
timeFrame: 24 weeks, 48 weeks
Secondary outcomes:
measure: Brain Function, Absolute Change Over 48 Weeks of N-acetyl Aspartate/Creatinine Ratio
timeFrame: 48 weeks
Other outcomes:
Locations:
city: Birmingham
country: United Kingdom
facility: Birmingham Heartlands Hospital:
city: Brighton
country: United Kingdom
facility: Brighton and Sussex University Hospital NHS Trust:
city: London:
country: United Kingdom
facility: St. Mary's Hospital
city: London
country: United Kingdom
facility: Kings College Hospital
city: London
country: United Kingdom
facility: Chelsea and Westminster Hospital NHS Trust
city: London
country: United Kingdom
facility: St. Thomas' Hospital
Study officials:
affiliation: Imperial College London
name: Alan Winston
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.