HIV, Impaired Cognition
Conditions
Keywords
HIV
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.
Interventions
DRUGstandard care
* atazanavir 300 mg daily * ritonavir 100 mg daily * tenofovir 245 mg daily\* * emtricitabine 200 mg daily\*
DRUGnovel treatment
* darunavir 800 mg daily * ritonavir 100 mg daily * lamivudine 300 mg daily\*\* and abacavir 600mgs daily\*\* * maraviroc 150 mg once daily
Sponsors
Pfizer
Imperial College London
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Cognitive Function, Global Cognitive Score (Z-score) | 24 weeks, 48 weeks | 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 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Brain Function, Absolute Change Over 48 Weeks of N-acetyl Aspartate/Creatinine Ratio | 48 weeks | 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. |
Countries
United Kingdom
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Standard Boosted Treatment with:
tenofovir disoproxil fumarate/emtricitabine 300/200mg atazanavir/ritonavir 300/100mg all once daily | 30 |
| Maraviroc-intesified Boosted Treatment with:
abacavir/lamivudine 600/300mg darunavir/ ritonavir 800/100 mg maraviroc 150mg all once daily | 30 |
| Total | 60 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Withdrawal by Subject | 3 | 1 |
Baseline characteristics
| Characteristic | Maraviroc-intesified Boosted | Total | Standard Boosted |
|---|---|---|---|
| Age, Continuous | 35 years | 33 years | 31 years |
| Baseline CD4+ cell count | 429 cells/ug STANDARD_DEVIATION 240 | 441 cells/ug STANDARD_DEVIATION 227 | 453 cells/ug STANDARD_DEVIATION 218 |
| Baseline HIV RNA | 51 copies/ml 10^3 | 46 copies/ml 10^3 | 45 copies/ml 10^3 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 6 Participants | 11 Participants | 5 Participants |
| Race (NIH/OMB) More than one race | 2 Participants | 4 Participants | 2 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 22 Participants | 45 Participants | 23 Participants |
| Region of Enrollment United Kingdom | 30 participants | 60 participants | 30 participants |
| Sex: Female, Male Female | 1 Participants | 2 Participants | 1 Participants |
| Sex: Female, Male Male | 29 Participants | 58 Participants | 29 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 30 | 0 / 30 |
| other Total, other adverse events | 0 / 30 | 0 / 30 |
| serious Total, serious adverse events | 0 / 30 | 0 / 30 |
Outcome results
Primary
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
Time frame: 24 weeks, 48 weeks
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Standard Boosted | Cognitive Function, Global Cognitive Score (Z-score) | 24 weeks | 0.15 z score | Standard Error 0.07 |
| Standard Boosted | Cognitive Function, Global Cognitive Score (Z-score) | 48 weeks | 0.16 z score | Standard Error 0.09 |
| Maraviroc-intesified Boosted | Cognitive Function, Global Cognitive Score (Z-score) | 24 weeks | 0.19 z score | Standard Error 0.07 |
| Maraviroc-intesified Boosted | Cognitive Function, Global Cognitive Score (Z-score) | 48 weeks | 0.25 z score | Standard Error 0.08 |
Comparison: 24 weeksp-value: 0.68Regression, Linear
Comparison: 48 weeksp-value: 0.43Regression, Linear
Secondary
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.
Time frame: 48 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Standard Boosted | Brain Function, Absolute Change Over 48 Weeks of N-acetyl Aspartate/Creatinine Ratio | 0.071 ratio of N-acetyl aspartate/creatin | Standard Deviation 0.157 |
| Maraviroc-intesified Boosted | Brain Function, Absolute Change Over 48 Weeks of N-acetyl Aspartate/Creatinine Ratio | -0.097 ratio of N-acetyl aspartate/creatin | Standard Deviation 0.185 |
p-value: 0.0009Regression, Linear