HIV, HIV-associated Neurocognitive Disorder, Neurotoxicity
Conditions
Keywords
HIV, HIV-associated neurocognitive disorder, neurotoxicity
Brief summary
In this study investigators will use a multi-modal imaging approach of MRS and fMRI to comprehensively assess the biological changes in the brain associated with EFV-based regimen (EFV/FTC/TDF), specifically alterations in the brain circuitry, function and local neurochemistry, and their correlation with neuropsychological function.
Detailed description
In a cohort of HIV-infected patients who are clinically stable on the commonly use regimen of EFV/emtricitabine (FTC)/truvada (TDF) or Atripla, investigators propose to replace the EFV component with an integrase inhibitor, Raltegravir (RAL), given as the RAL and FTC/TDF to evaluate the EFV-related neural alterations. This is a multidisciplinary study which will be lead by Dr. Nina Lin, in collaboration with the research teams of Dr. Alexander Lin, Director of the Center for Clinical Spectroscopy, and Dr. Emily Stern, Director of the Functional Neuroimaging Laboratory, both members of the Brigham and Women's Department of Radiology at Harvard Medical School, as well as Dr. Jane Epstein, a researcher in Dr. Stern's research group. Dr. Epstein is a staff psychiatrist at Brigham and Women's hospital with extensive experience and expertise in research on abnormalities of affective and motivational processing in the context of neuropsychiatric disorders. Investigators will utilize the established clinical research platform in the Infectious Disease outpatient clinical practice at the Brigham and Women's Hospital, where there is currently have many ongoing HIV-related studies and a large panel of HIV-infected patients motivated to be involved in clinically relevant research. Investigators propose to use advanced neuroimaging to measure biologically changes in the brain associated with long-term EFV use with the following specific aims: 1. Determine changes in neurometabolites measured by MRS in the brain associated with long-term EFV use 2. Assess for alterations in neural activity correlated with affective symptoms associated with EFV vs RAL use using fMRI, and their associations with changes in neurometabolites assessed by MRS, and with changes in cognition assessed by Trail Making and Digit Substitution Tests. 3. Determine changes in emotion, cognition and sleep quality after switching from EFV to RAL, and how they correlate with subject treatment preference. This clinical study will extend our current understanding of EFV neurotoxicity by further defining the nature of these biological changes. Further elucidation of the neurobiological underpinnings of EFV-induced CNS toxicity will have clinical relevance in improving the quality of life and drug adherence of HIV-infected patients on ART, especially among older patients or those with baseline neuropsychiatric disorders, whom at baseline are more vulnerable to neurocognitive decline from long-term HIV infection.
Interventions
DRUGRaltegravir
Switch from Atripla to Raltegravir 400mg BID + Truvada (FTC/TDF) for total of 8 weeks
Sponsors
Merck Sharp & Dohme LLC
Massachusetts General Hospital
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
BASIC_SCIENCE
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
1. Chronic HIV-infected individuals on suppressive regimen with EFV/FTC/TDF, for at least 6 months 2. Undetectable HIV-1 RNA virus load for at least 6 months 3. No co-infections with active hepatitis B and C 4. Presence of at least moderate symptoms on 2 out of 3 subcores on the DASS 5. No known active HIV-related and non-HIV related CNS infections 6. Estimated glomerular filtration rate (EGFR) \>60 ml/min 7. Consent to switching to EVG/COBI/FTC/TDF 8. Ages 18 - 65
Exclusion criteria
1. History of CNS opportunistic infections or active CNS infections 2. History of severe psychiatric disorder (excluding depression and anxiety) 3. History of chronic neurological disorders, such as epilepsy or multiple sclerosis 4. History of or current significant substance abuse or dependence and/or heavy alcohol use (\>12 oz/wk) 5. Any women who may be pregnant (positive urine pregnancy test or unprotected sex in 2 weeks prior to scan) or known to be pregnant 6. Contraindications to undergoing fMRI, including metallic implants, claustrophobia, and medical conditions or medications that significantly affect cerebral blood flow or function.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Neurometabolites Based on Magnetic Resonance Spectroscopy (MRS) | week 0 and week 8 | Assess the levels of neuro-metabolites measured by MRS at week 0 before switching to the efavirenz-based therapy. Two areas of the brain: 1) posterior cingulate gyrus and 2) anterior cingulate will be assessed for the levels of brain creatine (Cr), gamma-aminobutyric acid (GABA) and glutathione (GLU). |
| Neural Activation Networks Using Functional Magnetic Resonance Imaging (fMRI) | week 0 and week 8 | Assess changes in neural activation correlated with affective disturbances associated with EFV vs. RAL using fMRI employing a paradigm that probes affective symptomatologies typical with EFV use; anxiety/dysphoria and affective dysregulation, and their association with changes in cognitive function. Four brain regions of interests (ROIs) are specified to show the differential frontal-limbic activation patterns in the task-evoked neural responses to the 3 linear contrasts of Pre-/Post-/ Pre-vs. Post-switch: \[Negative Word vs. Neutral Word\] x \[No-Go Trial Block vs. Go Trial Block\]: anterior Frontal Pole (aFP), posterior Cingulate Gyrus (pCG), dorsal anterior Cingulate Gyrus (daCG), Left Hippocampus (LHC). A linear mixed-effects model is utilized to examine the effect sizes of the key Regimen/Condition contrasts, with the Subject factor as the random-effect, and Age incorporated as a co-variate of no interest. A z-score is the Mean with a SD=1 and Measure of Dispersion equal to 1. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Fasting Lipid Profile | week 0 and week 8 | Measure the change in fasting lipid panel prior to and after switching off EFV-based regimen. |
| Sleep Quality | week 0 and week 8 | Assess for changes in sleep pattern and quality prior to and after switching off EFV-based regimen through a self-administered Pittsburg Sleep Quality Index (PSQI). Measure consists of 19 items with each weighted on 0-3 scale and the sum produces a total score, which ranges from 0-21. The lower the score the healthier the sleep quality. |
| Other Neurometabolite Changes Measured by MRS | week 0 and week 8 | Use MRS to evaluate a fuller panel of known neurometabolites (in addition to the primary endpoints) to evaluate for prominent and significant changes associated with EFV use. |
| Markers of Immune Activation | week 0 and week 8 | Change in markers of immune activation and inflammation associated with change to RAL (ie, sCD14, IL-6, hsCRP, D-dimer, CRP, LPS, sCD163, EndoCab) |
| Change in Level of EFV and Metabolites | week 0 and week 8 | Correlate change in level of EFV and metabolites with neurocognitive and neuroimaging changes |
| ART Regimen Preference | week 0 and week 8 | Evaluate patient preference in ART regimen (Atripla, EFV/FTC/TDF versus RAL + FTC/TDF) through self-administered questionnaires. |
| Neurocognitive Changes Measured by a Panel of Indexes: WAIS-R, HAMD, DASS-21, FRSBE, STAI | week 0 and week 8 | Assess for changes in cognitive and affective function prior to and after switching off EFV-based regimen. Indexes used to access neurocognitive changes included: 1. Wechsler Adult Intelligence Scale (WAIS-R) Digital Symbol Substitution Test: sensitive to brain dmamage, dementia, age and depressive changes. Range of 0-100, the higher the score the better the person's performance 2. Hamilton Rating Scale for Depression (HAMD): Measure of depression. Score of 0-7 is normal, score of \>20 is moderate/severe depression 3. Depression Anxiety Stress Scale (DASS-21) the lower the score, the less severe depression, anxiety and stress. Scale range of 0-63 4. Frontal Systems Behavior Scale (FRSBE): Increased score indicates greater behavioral impairment associated with frontal systems, range 37.2 to 186 5. Spielberger state trait anxiety inventory (STAI): the higher the score the greater then anxiety level, range of 20 to 80. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Raltegravir All 10 participants were switched from Atripla to twice daily Raltegravir and Truvada (FTC/TDF) | 10 |
| Total | 10 |
Baseline characteristics
| Characteristic | Raltegravir |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 0 Participants |
| Age, Categorical Between 18 and 65 years | 10 Participants |
| Region of Enrollment United States | 10 participants |
| Sex: Female, Male Female | 4 Participants |
| Sex: Female, Male Male | 6 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 10 |
| other Total, other adverse events | 0 / 10 |
| serious Total, serious adverse events | 0 / 10 |
Outcome results
Primary
Neural Activation Networks Using Functional Magnetic Resonance Imaging (fMRI)
Assess changes in neural activation correlated with affective disturbances associated with EFV vs. RAL using fMRI employing a paradigm that probes affective symptomatologies typical with EFV use; anxiety/dysphoria and affective dysregulation, and their association with changes in cognitive function. Four brain regions of interests (ROIs) are specified to show the differential frontal-limbic activation patterns in the task-evoked neural responses to the 3 linear contrasts of Pre-/Post-/ Pre-vs. Post-switch: \[Negative Word vs. Neutral Word\] x \[No-Go Trial Block vs. Go Trial Block\]: anterior Frontal Pole (aFP), posterior Cingulate Gyrus (pCG), dorsal anterior Cingulate Gyrus (daCG), Left Hippocampus (LHC). A linear mixed-effects model is utilized to examine the effect sizes of the key Regimen/Condition contrasts, with the Subject factor as the random-effect, and Age incorporated as a co-variate of no interest. A z-score is the Mean with a SD=1 and Measure of Dispersion equal to 1.
Time frame: week 0 and week 8
Population: 8 of 10 enrolled patients passed QA testing to qualify for final fMRI data analyses. The 3 linear contrasts of Pre-switch/Post-switch/Pre- vs. Post-switch: \[Neg vs.Neu\] x \[No-Go vs. Go\] are reported as z-score (standardized effect size measures with SD=1). Z-score is obtained for each subject, group Z-score is obtained via a mixed-effects model.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Raltegravir | Neural Activation Networks Using Functional Magnetic Resonance Imaging (fMRI) | PreVsPostXNegVsNeuXNoGoVsGo: aFP | 3.19 z-score |
| Raltegravir | Neural Activation Networks Using Functional Magnetic Resonance Imaging (fMRI) | PreVsPostXNegVsNeuXNoGoVsGo: pCG | 3.00 z-score |
| Raltegravir | Neural Activation Networks Using Functional Magnetic Resonance Imaging (fMRI) | PreVsPostXNegVsNeuXNoGoVsGo: daCG | -2.53 z-score |
| Raltegravir | Neural Activation Networks Using Functional Magnetic Resonance Imaging (fMRI) | PreVsPostXNegVsNeuXNoGoVsGo:LHC | -3.64 z-score |
| Raltegravir | Neural Activation Networks Using Functional Magnetic Resonance Imaging (fMRI) | Pre: NegVsNeuXNoGoVsGo: aFP | 4.01 z-score |
| Raltegravir | Neural Activation Networks Using Functional Magnetic Resonance Imaging (fMRI) | Pre: NegVsNeuXNoGoVsGo:pCG | 3.61 z-score |
| Raltegravir | Neural Activation Networks Using Functional Magnetic Resonance Imaging (fMRI) | Pre: NegVsNeuXNoGoVsGo: daCG | -2.94 z-score |
| Raltegravir | Neural Activation Networks Using Functional Magnetic Resonance Imaging (fMRI) | Pre: NegVsNeuXNoGoVsGo: LHC | -3.07 z-score |
| Raltegravir | Neural Activation Networks Using Functional Magnetic Resonance Imaging (fMRI) | Post: NegVsNeuXNoGoVsGo: aFP | -3.03 z-score |
| Raltegravir | Neural Activation Networks Using Functional Magnetic Resonance Imaging (fMRI) | Post: NegVsNeuXNoGoVsGo: pCG | -3.13 z-score |
| Raltegravir | Neural Activation Networks Using Functional Magnetic Resonance Imaging (fMRI) | Post: NegVsNeuXNoGoVsGo: daCG | 3.65 z-score |
| Raltegravir | Neural Activation Networks Using Functional Magnetic Resonance Imaging (fMRI) | Post: NegVsNeuXNoGoVsGo: LHC | 2.88 z-score |
Primary
Neurometabolites Based on Magnetic Resonance Spectroscopy (MRS)
Assess the levels of neuro-metabolites measured by MRS at week 0 before switching to the efavirenz-based therapy. Two areas of the brain: 1) posterior cingulate gyrus and 2) anterior cingulate will be assessed for the levels of brain creatine (Cr), gamma-aminobutyric acid (GABA) and glutathione (GLU).
Time frame: week 0 and week 8
Population: The arbitrary units are expressed as the output from MRS software. While similar to concentration (mM) due to assumptions in the software, it is best expressed as arbitrary units for comparison from week 0 to week 8.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Raltegravir | Neurometabolites Based on Magnetic Resonance Spectroscopy (MRS) | Post-switch Anterior Cingulate Creatine | 14.34 arbitrary units | Standard Deviation 2.92 |
| Raltegravir | Neurometabolites Based on Magnetic Resonance Spectroscopy (MRS) | Pre-switch Posterior Cingulate Creatine | 19.38 arbitrary units | Standard Deviation 1.82 |
| Raltegravir | Neurometabolites Based on Magnetic Resonance Spectroscopy (MRS) | Post-switch Posterior Cingulate Creatine | 18.94 arbitrary units | Standard Deviation 4.01 |
| Raltegravir | Neurometabolites Based on Magnetic Resonance Spectroscopy (MRS) | Pre-switch Posterior Cingulate Glutamate | 27.83 arbitrary units | Standard Deviation 5.06 |
| Raltegravir | Neurometabolites Based on Magnetic Resonance Spectroscopy (MRS) | Post-switch Posterior Cingulate Glutamate | 24.95 arbitrary units | Standard Deviation 4.54 |
| Raltegravir | Neurometabolites Based on Magnetic Resonance Spectroscopy (MRS) | Pre-switch Posterior Cingulate GABA | 5.27 arbitrary units | Standard Deviation 0.74 |
| Raltegravir | Neurometabolites Based on Magnetic Resonance Spectroscopy (MRS) | Post-switch Posterior Cingulate GABA | 5.32 arbitrary units | Standard Deviation 1.85 |
| Raltegravir | Neurometabolites Based on Magnetic Resonance Spectroscopy (MRS) | Pre-switch Anterior Cingulate Creatine | 14.86 arbitrary units | Standard Deviation 2.18 |
| Raltegravir | Neurometabolites Based on Magnetic Resonance Spectroscopy (MRS) | Pre-switch Anterior Cingulate Glutamate | 19.09 arbitrary units | Standard Deviation 3.83 |
| Raltegravir | Neurometabolites Based on Magnetic Resonance Spectroscopy (MRS) | Post-switch Anterior Cingulate Glutamate | 22.25 arbitrary units | Standard Deviation 6.21 |
| Raltegravir | Neurometabolites Based on Magnetic Resonance Spectroscopy (MRS) | Pre-switch Anterior Cingulate GABA | 4.73 arbitrary units | Standard Deviation 1.55 |
| Raltegravir | Neurometabolites Based on Magnetic Resonance Spectroscopy (MRS) | Post-switch Anterior Cingulate GABA | 3.14 arbitrary units | Standard Deviation 2.12 |
Secondary
ART Regimen Preference
Evaluate patient preference in ART regimen (Atripla, EFV/FTC/TDF versus RAL + FTC/TDF) through self-administered questionnaires.
Time frame: week 0 and week 8
Population: Each participant was asked a single self-administered question on their ART preference and asked to chose one of the 3 answers; 1. prefer to take Atripla, 2. prefer RAL-based regimen (that they received in study) or 3. no preference.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Raltegravir | ART Regimen Preference | Prefer Raltegravir-based ART | 7 participants |
| Raltegravir | ART Regimen Preference | Prefer Atripla (EFV-based ART) | 0 participants |
| Raltegravir | ART Regimen Preference | No preference | 3 participants |
Secondary
Change in Level of EFV and Metabolites
Correlate change in level of EFV and metabolites with neurocognitive and neuroimaging changes
Time frame: week 0 and week 8
Population: Level of EFV (efavirenz) in Atripla and its two known metabolites known to cause cerebral side effects, 7-hydroxy (OH) EFV and 8-OH EFV, were measured in the plasma prior to switch off Atripla and after 8 weeks of RAL-based regimen (no EFV).
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Raltegravir | Change in Level of EFV and Metabolites | pre-switch detectable 7-OH and 8-OH EFV metablites | 9 participants |
| Raltegravir | Change in Level of EFV and Metabolites | post-switch detectable 7-OH and 8-OH EFVmetaboites | 1 participants |
Secondary
Fasting Lipid Profile
Measure the change in fasting lipid panel prior to and after switching off EFV-based regimen.
Time frame: week 0 and week 8
Population: Change in lipid panel pre- and post-switch to RAL-based regimen
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Raltegravir | Fasting Lipid Profile | pre-switch total cholesterol | 200.9 mg/dL | Standard Deviation 37.02 |
| Raltegravir | Fasting Lipid Profile | post-switch total cholesterol | 176.7 mg/dL | Standard Deviation 26.2 |
| Raltegravir | Fasting Lipid Profile | pre-switch HDL | 58.8 mg/dL | Standard Deviation 9.69 |
| Raltegravir | Fasting Lipid Profile | post-switch HDL | 53.1 mg/dL | Standard Deviation 13.42 |
| Raltegravir | Fasting Lipid Profile | pre-switch LDL | 118.8 mg/dL | Standard Deviation 31.56 |
| Raltegravir | Fasting Lipid Profile | post-switch LDL | 103.5 mg/dL | Standard Deviation 24.08 |
| Raltegravir | Fasting Lipid Profile | pre-switch triglyceride | 116.4 mg/dL | Standard Deviation 69.62 |
| Raltegravir | Fasting Lipid Profile | post-switch triglyceride | 100.6 mg/dL | Standard Deviation 54.52 |
Secondary
Markers of Immune Activation
Change in markers of immune activation and inflammation associated with change to RAL (ie, sCD14, IL-6, hsCRP, D-dimer, CRP, LPS, sCD163, EndoCab)
Time frame: week 0 and week 8
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Raltegravir | Markers of Immune Activation | pre-switch IL-6 | 1.49 pg/ml | Standard Deviation 0.68 |
| Raltegravir | Markers of Immune Activation | pre-switch sCD14 | 3652333.6 pg/ml | Standard Deviation 771769.196 |
| Raltegravir | Markers of Immune Activation | post-switch sCD14 | 3135828.52 pg/ml | Standard Deviation 791445.1417 |
| Raltegravir | Markers of Immune Activation | pre-switch IP-10 | 195.84 pg/ml | Standard Deviation 74.57 |
| Raltegravir | Markers of Immune Activation | post-switch IP-10 | 202.85 pg/ml | Standard Deviation 55.58 |
| Raltegravir | Markers of Immune Activation | pre-switch sCD163 | 672844 pg/ml | Standard Deviation 281620 |
| Raltegravir | Markers of Immune Activation | post-switch sCD163 | 733536 pg/ml | Standard Deviation 378.958 |
| Raltegravir | Markers of Immune Activation | pre-switch MCP-1 | 95.578 pg/ml | Standard Deviation 34.14 |
| Raltegravir | Markers of Immune Activation | post-switch MCP-1 | 92.794 pg/ml | Standard Deviation 56.25 |
| Raltegravir | Markers of Immune Activation | post-switch IL-6 | 1.69 pg/ml | Standard Deviation 0.89 |
| Raltegravir | Markers of Immune Activation | pre-switch TNFR1 | 771.18 pg/ml | Standard Deviation 145.46 |
| Raltegravir | Markers of Immune Activation | post-switch TNFR1 | 829.12 pg/ml | Standard Deviation 130.66 |
Secondary
Neurocognitive Changes Measured by a Panel of Indexes: WAIS-R, HAMD, DASS-21, FRSBE, STAI
Assess for changes in cognitive and affective function prior to and after switching off EFV-based regimen. Indexes used to access neurocognitive changes included: 1. Wechsler Adult Intelligence Scale (WAIS-R) Digital Symbol Substitution Test: sensitive to brain dmamage, dementia, age and depressive changes. Range of 0-100, the higher the score the better the person's performance 2. Hamilton Rating Scale for Depression (HAMD): Measure of depression. Score of 0-7 is normal, score of \>20 is moderate/severe depression 3. Depression Anxiety Stress Scale (DASS-21) the lower the score, the less severe depression, anxiety and stress. Scale range of 0-63 4. Frontal Systems Behavior Scale (FRSBE): Increased score indicates greater behavioral impairment associated with frontal systems, range 37.2 to 186 5. Spielberger state trait anxiety inventory (STAI): the higher the score the greater then anxiety level, range of 20 to 80.
Time frame: week 0 and week 8
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Raltegravir | Neurocognitive Changes Measured by a Panel of Indexes: WAIS-R, HAMD, DASS-21, FRSBE, STAI | pre-switch WAIS | 48.1 units on a scale | Standard Deviation 12.53838551 |
| Raltegravir | Neurocognitive Changes Measured by a Panel of Indexes: WAIS-R, HAMD, DASS-21, FRSBE, STAI | post-switch WAIS | 53.5 units on a scale | Standard Deviation 12.00231459 |
| Raltegravir | Neurocognitive Changes Measured by a Panel of Indexes: WAIS-R, HAMD, DASS-21, FRSBE, STAI | pre-switch FRSBE | 79.2 units on a scale | Standard Deviation 13.07074766 |
| Raltegravir | Neurocognitive Changes Measured by a Panel of Indexes: WAIS-R, HAMD, DASS-21, FRSBE, STAI | post-switch FRSBE | 72.4 units on a scale | Standard Deviation 9.834180754 |
| Raltegravir | Neurocognitive Changes Measured by a Panel of Indexes: WAIS-R, HAMD, DASS-21, FRSBE, STAI | pre-switch HAMD | 4.7 units on a scale | Standard Deviation 3.860051813 |
| Raltegravir | Neurocognitive Changes Measured by a Panel of Indexes: WAIS-R, HAMD, DASS-21, FRSBE, STAI | post-switch HAMD | 2.7 units on a scale | Standard Deviation 3.020301677 |
| Raltegravir | Neurocognitive Changes Measured by a Panel of Indexes: WAIS-R, HAMD, DASS-21, FRSBE, STAI | pre-switch DASS depression | 6.4 units on a scale | Standard Deviation 9.834180754 |
| Raltegravir | Neurocognitive Changes Measured by a Panel of Indexes: WAIS-R, HAMD, DASS-21, FRSBE, STAI | post-switch DASS depression | 3.4 units on a scale | Standard Deviation 3.777124126 |
| Raltegravir | Neurocognitive Changes Measured by a Panel of Indexes: WAIS-R, HAMD, DASS-21, FRSBE, STAI | pre-switch STAI | 29.4 units on a scale | Standard Deviation 5.481281278 |
| Raltegravir | Neurocognitive Changes Measured by a Panel of Indexes: WAIS-R, HAMD, DASS-21, FRSBE, STAI | post-switch STAI | 27.2 units on a scale | Standard Deviation 6.528569692 |
Secondary
Other Neurometabolite Changes Measured by MRS
Use MRS to evaluate a fuller panel of known neurometabolites (in addition to the primary endpoints) to evaluate for prominent and significant changes associated with EFV use.
Time frame: week 0 and week 8
Population: The arbitrary units are expressed as the output from MRS software. While similar to concentration (mM) due to assumptions in the software, it is best expressed as arbitrary units for comparison from week 0 to week 8.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Raltegravir | Other Neurometabolite Changes Measured by MRS | Post-switch Posterior Cingulate Aspartate | 3.31 arbitrary units | Standard Deviation 0.97 |
| Raltegravir | Other Neurometabolite Changes Measured by MRS | Pre-switch Anterior Cingulate Glutathione | 4.25 arbitrary units | Standard Deviation 1.01 |
| Raltegravir | Other Neurometabolite Changes Measured by MRS | Pre-switch Posterior Cingulate Glutathione | 5.11 arbitrary units | Standard Deviation 1.18 |
| Raltegravir | Other Neurometabolite Changes Measured by MRS | Post-switch Posterior Cingulate Glutathione | 4.70 arbitrary units | Standard Deviation 1.51 |
| Raltegravir | Other Neurometabolite Changes Measured by MRS | Pre-switch Posterior Cingulate Aspartate | 4.32 arbitrary units | Standard Deviation 0.95 |
| Raltegravir | Other Neurometabolite Changes Measured by MRS | Post-switch Anterior Cingulate Glutathione | 3.18 arbitrary units | Standard Deviation 1.08 |
| Raltegravir | Other Neurometabolite Changes Measured by MRS | Pre-switch Anterior Cingulate Aspartate | 3.15 arbitrary units | Standard Deviation 1.28 |
| Raltegravir | Other Neurometabolite Changes Measured by MRS | Post-switch Anterior Cingulate Aspartate | 2.18 arbitrary units | Standard Deviation 1.61 |
Secondary
Sleep Quality
Assess for changes in sleep pattern and quality prior to and after switching off EFV-based regimen through a self-administered Pittsburg Sleep Quality Index (PSQI). Measure consists of 19 items with each weighted on 0-3 scale and the sum produces a total score, which ranges from 0-21. The lower the score the healthier the sleep quality.
Time frame: week 0 and week 8
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Raltegravir | Sleep Quality | pre-switch PSQI index | 5.3 units on a scale | Standard Deviation 3.06 |
| Raltegravir | Sleep Quality | post-switch PSQI index | 3.8 units on a scale | Standard Deviation 1.99 |