Trial Outcomes & Findings for Efficacy of Neuro-HAART in Patients With HIV (NCT NCT01434654)
NCT ID: NCT01434654
Last Updated: 2016-08-09
Results Overview
Change in overall neurocognitive performance, defined as a global neurocognitive z-score, after a 12-month period of observation, between HIV positive patients taking antiretroviral regimens categorized as being either of high or low CNS penetration. To derive this score, 1) raw scores obtained from a 5-domain brief neurocognitive battery were converted to age-corrected z-scores (M=0, Standard Deviation=1) and 2) the set of individual subtest z-scores were averaged to generate a single composite (global) z-score for each subject. Lower (negative) scores therefore indicate greater levels of cognitive impairment.
Recruitment status
TERMINATED
Target enrollment
19 participants
Primary outcome timeframe
Change from baseline Neuropsychological testing at 6 and 12 months
Results posted on
2016-08-09
Participant Flow
Participants were recruited from St Vincent's Hospital and/or referred from tertiary sexual health centres over the period January 2012 to June 2013.
Participant milestones
| Measure |
Non Neuro-HAART (Low CNS Penetrance)
Participants will be assessed based on their current Highly Active Antiretroviral Treatment (HAART). A scoring system is utilised to determine if their current treatment has high Central Nervous System (CNS) penetrance or low CNS penetrance. This will determine which study cohort they are randomised to. No treatment adjustments or changes will be made, they will remain on their usual HAART regimen.
|
Neuro-HAART (High CNS Penetrance)
Participants will be assessed based on their current Highly Active Antiretroviral Treatment (HAART). A scoring system is utilised to determine if their current treatment has high Central Nervous System (CNS) penetrance or low CNS penetrance. This will determine which study cohort they are randomised to. No treatment adjustments or changes will be made, they will remain on their usual HAART regimen.
|
|---|---|---|
|
Overall Study
STARTED
|
7
|
12
|
|
Overall Study
COMPLETED
|
5
|
12
|
|
Overall Study
NOT COMPLETED
|
2
|
0
|
Reasons for withdrawal
| Measure |
Non Neuro-HAART (Low CNS Penetrance)
Participants will be assessed based on their current Highly Active Antiretroviral Treatment (HAART). A scoring system is utilised to determine if their current treatment has high Central Nervous System (CNS) penetrance or low CNS penetrance. This will determine which study cohort they are randomised to. No treatment adjustments or changes will be made, they will remain on their usual HAART regimen.
|
Neuro-HAART (High CNS Penetrance)
Participants will be assessed based on their current Highly Active Antiretroviral Treatment (HAART). A scoring system is utilised to determine if their current treatment has high Central Nervous System (CNS) penetrance or low CNS penetrance. This will determine which study cohort they are randomised to. No treatment adjustments or changes will be made, they will remain on their usual HAART regimen.
|
|---|---|---|
|
Overall Study
Withdrawal by Subject
|
1
|
0
|
|
Overall Study
Lost to Follow-up
|
1
|
0
|
Baseline Characteristics
Efficacy of Neuro-HAART in Patients With HIV
Baseline characteristics by cohort
| Measure |
Non Neuro-HAART (Low CNS Penetrance)
n=5 Participants
Participants will be assessed based on their current Highly Active Antiretroviral Treatment (HAART). A scoring system is utilised to determine if their current treatment has high Central Nervous System (CNS) penetrance or low CNS penetrance. This will determine which study cohort they are randomised to. No treatment adjustments or changes will be made, they will remain on their usual HAART regimen.
|
Neuro-HAART (High CNS Penetrance)
n=12 Participants
Participants will be assessed based on their current Highly Active Antiretroviral Treatment (HAART). A scoring system is utilised to determine if their current treatment has high Central Nervous System (CNS) penetrance or low CNS penetrance. This will determine which study cohort they are randomised to. No treatment adjustments or changes will be made, they will remain on their usual HAART regimen.
|
Total
n=17 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
50.2 years
STANDARD_DEVIATION 7.8 • n=99 Participants
|
55.4 years
STANDARD_DEVIATION 8.6 • n=107 Participants
|
53.9 years
STANDARD_DEVIATION 8.5 • n=206 Participants
|
|
Sex: Female, Male
Female
|
0 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
0 Participants
n=206 Participants
|
|
Sex: Female, Male
Male
|
5 Participants
n=99 Participants
|
12 Participants
n=107 Participants
|
17 Participants
n=206 Participants
|
|
Race/Ethnicity, Customized
Caucasian
|
4 participants
n=99 Participants
|
11 participants
n=107 Participants
|
15 participants
n=206 Participants
|
|
Race/Ethnicity, Customized
Asian
|
1 participants
n=99 Participants
|
1 participants
n=107 Participants
|
2 participants
n=206 Participants
|
|
Region of Enrollment
Australia
|
5 participants
n=99 Participants
|
12 participants
n=107 Participants
|
17 participants
n=206 Participants
|
|
Education
|
14.4 years
STANDARD_DEVIATION 3.4 • n=99 Participants
|
12.2 years
STANDARD_DEVIATION 2.7 • n=107 Participants
|
12.8 years
STANDARD_DEVIATION 2.7 • n=206 Participants
|
|
Premorbid intelligence quotient (IQ)
|
104.2 units on a scale
STANDARD_DEVIATION 18.7 • n=99 Participants
|
102.5 units on a scale
STANDARD_DEVIATION 12.6 • n=107 Participants
|
103.0 units on a scale
STANDARD_DEVIATION 14.1 • n=206 Participants
|
|
Nadir cluster of differentiation 4 (CD4)
|
400 cells/mm3
n=99 Participants
|
115 cells/mm3
n=107 Participants
|
200 cells/mm3
n=206 Participants
|
|
Current CD4
|
943 cells/mm3
n=99 Participants
|
583 cells/mm3
n=107 Participants
|
684 cells/mm3
n=206 Participants
|
|
HIV-Associated Neurocognitive Disorder (HAND) status
Normal/Unimpaired
|
1 participants
n=99 Participants
|
2 participants
n=107 Participants
|
3 participants
n=206 Participants
|
|
HIV-Associated Neurocognitive Disorder (HAND) status
Asymptomatic Neurocognitive Impairment (ANI)
|
2 participants
n=99 Participants
|
7 participants
n=107 Participants
|
9 participants
n=206 Participants
|
|
HIV-Associated Neurocognitive Disorder (HAND) status
Mild Neurocognitive Disorder (MND)
|
1 participants
n=99 Participants
|
3 participants
n=107 Participants
|
4 participants
n=206 Participants
|
|
HIV-Associated Neurocognitive Disorder (HAND) status
HIV-Associated Dementia (HAD)
|
1 participants
n=99 Participants
|
0 participants
n=107 Participants
|
1 participants
n=206 Participants
|
PRIMARY outcome
Timeframe: Change from baseline Neuropsychological testing at 6 and 12 monthsPopulation: Modified intent-to-treat analysis. All enrolled participants were included aside n=2 low CNS penetrance with baseline data only (1 lost to follow-up, 1 withdrew before 6-months).
Change in overall neurocognitive performance, defined as a global neurocognitive z-score, after a 12-month period of observation, between HIV positive patients taking antiretroviral regimens categorized as being either of high or low CNS penetration. To derive this score, 1) raw scores obtained from a 5-domain brief neurocognitive battery were converted to age-corrected z-scores (M=0, Standard Deviation=1) and 2) the set of individual subtest z-scores were averaged to generate a single composite (global) z-score for each subject. Lower (negative) scores therefore indicate greater levels of cognitive impairment.
Outcome measures
| Measure |
Non Neuro-HAART (Low CNS Penetrance)
n=5 Participants
Participants will be assessed based on their current Highly Active Antiretroviral Treatment (HAART). A scoring system is utilised to determine if their current treatment has high Central Nervous System (CNS) penetrance or low CNS penetrance. This will determine which study cohort they are allocated to. No treatment adjustments or changes will be made, they will remain on their usual HAART regimen.
|
Neuro-HAART (High CNS Penetrance)
n=12 Participants
Participants will be assessed based on their current Highly Active Antiretroviral Treatment (HAART). A scoring system is utilised to determine if their current treatment has high Central Nervous System (CNS) penetrance or low CNS penetrance. This will determine which study cohort they are allocated to. No treatment adjustments or changes will be made, they will remain on their usual HAART regimen.
|
|---|---|---|
|
Change in Neurocognitive Functioning
Baseline
|
-0.26 Global neurocognitive z-score
Standard Error 0.27
|
-0.80 Global neurocognitive z-score
Standard Error 0.17
|
|
Change in Neurocognitive Functioning
6 months
|
-0.09 Global neurocognitive z-score
Standard Error 0.27
|
-0.63 Global neurocognitive z-score
Standard Error 0.17
|
|
Change in Neurocognitive Functioning
12 months
|
-0.07 Global neurocognitive z-score
Standard Error 0.27
|
-0.61 Global neurocognitive z-score
Standard Error 0.17
|
SECONDARY outcome
Timeframe: Baseline and 12 monthsPopulation: n=1 participant in high CNS penetrance arm did not return for 12-months follow-up visit. Their baseline data were therefore excluded from analysis.
Change in major cerebral metabolites in the basal ganglia, as measured by 1H-Magnetic Resonance Spectroscopy (MRS), after a 12 month period of observation. Spectra were acquired on a Phillips Achieva 3T MRI scanner using point-resolved spectroscopy (PRESS) sequence with short echo time (TE). jMRUI/AMARES algorithm was used to process spectra. Metabolite ratios were calculated for the following metabolites: N-acetyl aspartate (NAA), choline (Cho), creatine (Cr), myo-inositol (mIo), in relation to internal water (H20) as standard.
Outcome measures
| Measure |
Non Neuro-HAART (Low CNS Penetrance)
n=5 Participants
Participants will be assessed based on their current Highly Active Antiretroviral Treatment (HAART). A scoring system is utilised to determine if their current treatment has high Central Nervous System (CNS) penetrance or low CNS penetrance. This will determine which study cohort they are allocated to. No treatment adjustments or changes will be made, they will remain on their usual HAART regimen.
|
Neuro-HAART (High CNS Penetrance)
n=11 Participants
Participants will be assessed based on their current Highly Active Antiretroviral Treatment (HAART). A scoring system is utilised to determine if their current treatment has high Central Nervous System (CNS) penetrance or low CNS penetrance. This will determine which study cohort they are allocated to. No treatment adjustments or changes will be made, they will remain on their usual HAART regimen.
|
|---|---|---|
|
Change in MRS Cerebral Metabolite Ratios in Basal Ganglia
Cr 12 Months
|
3.20 Ratio
Standard Error 0.18
|
3.27 Ratio
Standard Error 0.12
|
|
Change in MRS Cerebral Metabolite Ratios in Basal Ganglia
NAA Baseline
|
4.14 Ratio
Standard Error 0.20
|
4.00 Ratio
Standard Error 0.13
|
|
Change in MRS Cerebral Metabolite Ratios in Basal Ganglia
NAA 12 months
|
3.96 Ratio
Standard Error 0.20
|
3.99 Ratio
Standard Error 0.13
|
|
Change in MRS Cerebral Metabolite Ratios in Basal Ganglia
Cr Baseline
|
3.18 Ratio
Standard Error 0.18
|
3.03 Ratio
Standard Error 0.12
|
|
Change in MRS Cerebral Metabolite Ratios in Basal Ganglia
Cho Baseline
|
1.81 Ratio
Standard Error 0.16
|
1.79 Ratio
Standard Error 0.11
|
|
Change in MRS Cerebral Metabolite Ratios in Basal Ganglia
Cho 12 Months
|
1.78 Ratio
Standard Error 0.16
|
1.72 Ratio
Standard Error 0.11
|
|
Change in MRS Cerebral Metabolite Ratios in Basal Ganglia
mIo Baseline
|
1.22 Ratio
Standard Error 0.21
|
1.27 Ratio
Standard Error 0.14
|
|
Change in MRS Cerebral Metabolite Ratios in Basal Ganglia
mIo 12 Months
|
1.12 Ratio
Standard Error 0.21
|
1.18 Ratio
Standard Error 0.14
|
SECONDARY outcome
Timeframe: Baseline and 12 monthsPopulation: n=1 participant in high CNS penetrance arm did not return for 12-months follow-up visit. Their baseline data were therefore excluded from analysis.
Change in major cerebral metabolites in the frontal white matter, as measured by 1H-Magnetic Resonance Spectroscopy (MRS), between baseline and 12-months. Spectra were acquired on a Phillips Achieva 3T MRI scanner using point-resolved spectroscopy (PRESS) sequence with short TE. jMRUI/AMARES algorithm was used to process spectra. Metabolite ratios were calculated for the following metabolites: N-acetyl aspartate (NAA), choline (Cho), creatine (Cr), myo-inositol (mIo), glutamate/glutamine complex (Glx), in relation to internal H20 as standard.
Outcome measures
| Measure |
Non Neuro-HAART (Low CNS Penetrance)
n=5 Participants
Participants will be assessed based on their current Highly Active Antiretroviral Treatment (HAART). A scoring system is utilised to determine if their current treatment has high Central Nervous System (CNS) penetrance or low CNS penetrance. This will determine which study cohort they are allocated to. No treatment adjustments or changes will be made, they will remain on their usual HAART regimen.
|
Neuro-HAART (High CNS Penetrance)
n=11 Participants
Participants will be assessed based on their current Highly Active Antiretroviral Treatment (HAART). A scoring system is utilised to determine if their current treatment has high Central Nervous System (CNS) penetrance or low CNS penetrance. This will determine which study cohort they are allocated to. No treatment adjustments or changes will be made, they will remain on their usual HAART regimen.
|
|---|---|---|
|
Change in MRS Cerebral Metabolite Ratios in Frontal White Matter
NAA Baseline
|
4.39 Ratio
Standard Error 0.22
|
4.38 Ratio
Standard Error 0.15
|
|
Change in MRS Cerebral Metabolite Ratios in Frontal White Matter
NAA 12 Months
|
4.74 Ratio
Standard Error 0.22
|
4.32 Ratio
Standard Error 0.15
|
|
Change in MRS Cerebral Metabolite Ratios in Frontal White Matter
Cr Baseline
|
2.77 Ratio
Standard Error 0.19
|
3.09 Ratio
Standard Error 0.12
|
|
Change in MRS Cerebral Metabolite Ratios in Frontal White Matter
Cr 12 Months
|
3.29 Ratio
Standard Error 0.19
|
3.16 Ratio
Standard Error 0.12
|
|
Change in MRS Cerebral Metabolite Ratios in Frontal White Matter
Cho Baseline
|
2.25 Ratio
Standard Error 0.13
|
2.33 Ratio
Standard Error 0.09
|
|
Change in MRS Cerebral Metabolite Ratios in Frontal White Matter
Cho 12 Months
|
2.50 Ratio
Standard Error 0.13
|
2.31 Ratio
Standard Error 0.08
|
|
Change in MRS Cerebral Metabolite Ratios in Frontal White Matter
mIo Baseline
|
1.06 Ratio
Standard Error 0.09
|
1.05 Ratio
Standard Error 0.06
|
|
Change in MRS Cerebral Metabolite Ratios in Frontal White Matter
mIo 12 Months
|
1.19 Ratio
Standard Error 0.09
|
1.23 Ratio
Standard Error 0.06
|
|
Change in MRS Cerebral Metabolite Ratios in Frontal White Matter
Glx Baseline
|
2.26 Ratio
Standard Error 0.16
|
2.13 Ratio
Standard Error 0.11
|
|
Change in MRS Cerebral Metabolite Ratios in Frontal White Matter
Glx 12 Months
|
2.13 Ratio
Standard Error 0.19
|
1.96 Ratio
Standard Error 0.11
|
SECONDARY outcome
Timeframe: Baseline to 12 MonthsPopulation: Data presented for n=5 participants with detectable CSF ARV concentrations who had lumbar puncture at Baseline and 12 months. The pre-specified analysis was not conducted as nevirapine, raltegravir, and darunavir were the only ARVs detected in CSF, and of these, only nevirapine was detected above the minimum threshold (set at \>50 ug/L).
To measure plateaux CSF ARV concentrations. This will identify the proportion of patients achieving levels of specific ARVs capable of inhibiting 95% of in vitro viral replication (IC95).
Outcome measures
| Measure |
Non Neuro-HAART (Low CNS Penetrance)
n=1 Participants
Participants will be assessed based on their current Highly Active Antiretroviral Treatment (HAART). A scoring system is utilised to determine if their current treatment has high Central Nervous System (CNS) penetrance or low CNS penetrance. This will determine which study cohort they are allocated to. No treatment adjustments or changes will be made, they will remain on their usual HAART regimen.
|
Neuro-HAART (High CNS Penetrance)
n=4 Participants
Participants will be assessed based on their current Highly Active Antiretroviral Treatment (HAART). A scoring system is utilised to determine if their current treatment has high Central Nervous System (CNS) penetrance or low CNS penetrance. This will determine which study cohort they are allocated to. No treatment adjustments or changes will be made, they will remain on their usual HAART regimen.
|
|---|---|---|
|
Cerebrospinal Fluid
Nevirapine Baseline
|
NA ug/L
Standard Error NA
No participants in this study arm had detectable nevirapine CSF concentrations at baseline. Therefore no data available to report.
|
1161.5 ug/L
Standard Error 101.5
|
|
Cerebrospinal Fluid
Nevirapine 12 months
|
NA ug/L
Standard Error NA
No participants in this study arm had detectable nevirapine CSF concentrations at 12 months. Therefore no data available to report.
|
1445 ug/L
Standard Error 234
|
|
Cerebrospinal Fluid
Raltegravir Baseline
|
38 ug/L
Standard Error NA
n=1 participant in this study arm had detectable raltegravir CSF concentrations at baseline. Therefore SE not applicable.
|
39 ug/L
Standard Error NA
n=1 participant in this study arm had detectable raltegravir CSF concentrations at baseline. Therefore SE not applicable.
|
|
Cerebrospinal Fluid
Raltegravir 12 months
|
32 ug/L
Standard Error NA
n=1 participant in this study arm had detectable raltegravir CSF concentrations at 12 months. Therefore SE not applicable.
|
NA ug/L
Standard Error NA
No participants in this study arm had detectable raltegravir CSF concentrations at 12 months. Therefore no data available to report.
|
|
Cerebrospinal Fluid
Darunavir Baseline
|
46 ug/L
Standard Error NA
n=1 participant in this study arm had detectable darunavir CSF concentrations at baseline. Therefore SE not applicable.
|
39 ug/L
Standard Error NA
n=1 participant in this study arm had detectable darunavir CSF concentrations at baseline. Therefore SE not applicable.
|
|
Cerebrospinal Fluid
Darunavir 12 months
|
NA ug/L
Standard Error NA
No participants in this study arm had detectable darunavir CSF concentrations at 12 months. Therefore no data available to report.
|
50 ug/L
Standard Error NA
n=1 participant in this study arm had detectable darunavir CSF concentrations at 12 months. Therefore SE not applicable.
|
Adverse Events
Non Neuro-HAART (Low CNS Penetrance)
Serious events: 0 serious events
Other events: 2 other events
Deaths: 0 deaths
Neuro-HAART (High CNS Penetrance)
Serious events: 0 serious events
Other events: 5 other events
Deaths: 0 deaths
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
Non Neuro-HAART (Low CNS Penetrance)
n=7 participants at risk
Participants will be assessed based on their current Highly Active Antiretroviral Treatment (HAART). A scoring system is utilised to determine if their current treatment has high Central Nervous System (CNS) penetrance or low CNS penetrance. This will determine which study cohort they are randomised to. No treatment adjustments or changes will be made, they will remain on their usual HAART regimen.
|
Neuro-HAART (High CNS Penetrance)
n=12 participants at risk
Participants will be assessed based on their current Highly Active Antiretroviral Treatment (HAART). A scoring system is utilised to determine if their current treatment has high Central Nervous System (CNS) penetrance or low CNS penetrance. This will determine which study cohort they are randomised to. No treatment adjustments or changes will be made, they will remain on their usual HAART regimen.
|
|---|---|---|
|
Investigations
Post-lumbar puncture headache
|
14.3%
1/7 • Number of events 1 • Baseline to 12 Months
|
8.3%
1/12 • Number of events 1 • Baseline to 12 Months
|
|
Surgical and medical procedures
Laser eye surgery
|
14.3%
1/7 • Number of events 1 • Baseline to 12 Months
|
0.00%
0/12 • Baseline to 12 Months
|
|
Renal and urinary disorders
Kidney stones and stent insertion
|
14.3%
1/7 • Number of events 1 • Baseline to 12 Months
|
0.00%
0/12 • Baseline to 12 Months
|
|
Skin and subcutaneous tissue disorders
Rash and excema
|
0.00%
0/7 • Baseline to 12 Months
|
8.3%
1/12 • Number of events 1 • Baseline to 12 Months
|
|
Infections and infestations
Influenza
|
14.3%
1/7 • Number of events 1 • Baseline to 12 Months
|
8.3%
1/12 • Number of events 1 • Baseline to 12 Months
|
|
Skin and subcutaneous tissue disorders
Staphylococcal infection
|
0.00%
0/7 • Baseline to 12 Months
|
8.3%
1/12 • Number of events 1 • Baseline to 12 Months
|
|
Investigations
Skin biopsy
|
0.00%
0/7 • Baseline to 12 Months
|
8.3%
1/12 • Number of events 1 • Baseline to 12 Months
|
|
Surgical and medical procedures
Basal cell carcinoma removal
|
0.00%
0/7 • Baseline to 12 Months
|
8.3%
1/12 • Number of events 1 • Baseline to 12 Months
|
|
Musculoskeletal and connective tissue disorders
Muscle strain
|
0.00%
0/7 • Baseline to 12 Months
|
8.3%
1/12 • Number of events 1 • Baseline to 12 Months
|
|
Metabolism and nutrition disorders
Vitamin D deficiency
|
14.3%
1/7 • Number of events 1 • Baseline to 12 Months
|
0.00%
0/12 • Baseline to 12 Months
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place