A Study of the Neurological Effects of Adding Maraviroc to HAART Regimen in Patients With HIV (HANDmac)

• Sponsor: Bruce Brew (Other)
• Overall Status: Completed
• CT.gov ID: NCT01449006
• Collaborator: ViiV Healthcare (Industry)
• Enrollment: 19
• Locations: 2
• Arms: 2
• Duration (Months): 35
• Patients Per Site: 9.5
• Patients Per Site Per Month: 0.3

Study Details

Study Description

Brief Summary

HIV related cognitive impairment still occurs despite highly active antiretroviral therapy (HAART). HIV disease affects the brain in 20-40% of patients with advancing HIV disease; leading to varying degrees of cognitive impairment, recently termed HIV associated neurocognitive disorders (HAND). HAND may occur in patients who are virally suppressed in both blood and CSF.

Patients with HIV Associated Neurocognitive Disorders (HAND) who are virally suppressed in both their blood and cerebrospinal fluid (CSF), whilst on a highly active antiretroviral therapy (HAART) regimen may have significant cognitive improvement with HAART intensification with the medication Maraviroc; compared to those who remain on their existing regimen.

This study will be a prospective, interventional, randomised and unblinded controlled clinical trial. The aim of this study will be to determine whether HAART intensification with the medication Maraviroc, leads to significant improvement in HIV associated neurocognitive disorders (HAND).

Patients with the recent progression (within 6 months) of HAND (validated by neuropsychological assessment) on HAART, who are virally suppressed (<50 copies per ml) in blood and CSF will be randomised to have their existing HAART regimen intensified with Maraviroc, or not. The control arm will remain on their medication regimen as prescribed. The target is to enrol 70 patients into the control group, and 70 patients into the Maraviroc intensification group.

Patients will undergo baseline neuropsychological testing, MRI, blood tests, and cerebrospinal fluid (CSF) tests (via a lumbar puncture). The methods used to determine the effectiveness of adding Maraviroc, will include further neuropsychological assessment at 6 months, and neuropsychological assessment, MRI and CSF assessment again at 12 months.

Neuropsychological testing completed at 6 and 12 months will be completed by a "blind assessor", in that they will have no knowledge of which arm (treatment or control) the participant is enrolled in.

An evaluation (neuropsychological testing) will be performed should the patient deteriorate during the course of the study, as recognised by the patient's managing physician.

At the end of the study protocol (12 months) the patient's HAART therapy will be managed by their primary physician.

Condition or Disease	Intervention/Treatment	Phase
Human Immunodeficiency Virus (HIV); HIV Associated Neurocognitive Disorders (HAND)	Drug: Maraviroc	Phase 4

Study Design

• Study Type: Interventional
• Actual Enrollment: 19 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Randomised Controlled Clinical Trial of the Efficacy of HAART Intensification With Maraviroc in HIV Virally Suppressed Patients With Cognitive Impairment
• Study Start Date: Oct 1, 2011
• Actual Primary Completion Date: Sep 1, 2014
• Actual Study Completion Date: Sep 1, 2014

Arms and Interventions

Arm	Intervention/Treatment
No Intervention: Standard of care HAART regimen Participants randomised to this arm of the trial will remain on their usual prescribed HAART regimen.
Experimental: Maraviroc Participants randomised to this arm will remain on their usual prescribed HAART regimen, with the addition of Maraviroc. Maraviroc will be prescribed according to the Product Information Sheet, with consideration given to background therapy.	Drug: Maraviroc; Maraviroc oral tablet. Dosage: 150 mg twice daily, 300 mg twice daily, or 600 mg twice daily. Dosing will be dependent on the participant's background HAART therapy, and will be in accordance with the product information sheet.; Other Names: Celsentri

Outcome Measures

Primary Outcome Measures

1. Change in Neurocognitive Functioning [Baseline, 6-months and 12-months]

   Change in overall neurocognitive performance, defined as a global neurocognitive z-score, over the study time-period (baseline, 6-months, 12-months). To derive this score, 1) raw scores obtained from a 5-domain brief neurocognitive battery were converted to age-corrected z-scores (M=0, SD=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.

Secondary Outcome Measures

1. Change in CSF Neopterin Concentration [Baseline and 12-months]

   Change in concentration of the CSF neuroinflammatory marker neopterin (measured in nmol/L) from baseline to 12-months.

2. Change in MRS Cerebral Metabolite Ratios in Basal Ganglia [Baseline and 12 months]

   Change in major cerebral metabolites in the basal ganglia, 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 echot 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.

3. Change in MRS Cerebral Metabolite Ratios in Frontal White Matter [Baseline and 12 months]

   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 H2O as standard.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• HIV Positive

• On HAART, with plasma viral load < 50 copies/ml for previous 12 months or more

• Able to provide informed consent

• HAND diagnosis, with symptom progression within previous 6 months

Exclusion Criteria:

• Non-HIV related neurological disorders and active central nervous system (CNS) opportunistic infection (as assessed by full blood count, electrolytes, creatinine, glucose, liver funciton tests, cryptococcal antigen, venereal disease research laboratory (VDRL), MRI brain scan and CSF analysis for cell count, protein, glucose, culture, VDRL and cryptococcal antigen)

• Psychiatric disorders on the psychiatric axis

• Current major depression

• Current substance use disorder, or severe substance use disorder within 12 months of study entry

• Active Hepatitis C Virus (HCV) (detectable HCV RNA)

• History of loss of consciousness > 1 hour

• Non-proficient in English

• Medications known to pharmacologically interact with antiretrovirals (ARVs)

• Currently taking an entry inhibitor

• Pregnancy (as assessed by the urine pregnancy test)

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	St. Vincent's Hospital	Sydney	New South Wales	Australia	2010
2	The Alfred Hospital	Melbourne	Victoria	Australia	3181

Sponsors and Collaborators

• Bruce Brew
• ViiV Healthcare

Investigators

• Principal Investigator: Bruce J Brew, MBBS, PhD, St Vincent's Hospital - Sydney, Australia

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Bruce Brew, Professor, St. Vincent's Hospital-Manhattan
• ClinicalTrials.gov Identifier: NCT01449006
• Other Study ID Numbers: 11/066; 114560
• First Posted: Oct 7, 2011
• Last Update Posted: Feb 27, 2019
• Last Verified: Feb 1, 2019

• Keywords provided by Bruce Brew, Professor, St. Vincent's Hospital-Manhattan: HIV; HAND; Maraviroc; Neurocognitive; Neurology; Human Immunodeficiency Virus; HIV Associated Neurocognitive Disorders
• Additional relevant MeSH terms: Acquired Immunodeficiency Syndrome; HIV Infections; Immunologic Deficiency Syndromes; Neurocognitive Disorders; Maraviroc

Study Results

Participant Flow

Recruitment Details	Participants were recruited from St Vincent's Hospital and/or referred from tertiary sexual health centres over the period January 2012 to June 2013.
Pre-assignment Detail	Two enrolled participants failed screening (1 HCV+, 1 not cognitively impaired)

Arm/Group Title	Standard of Care HAART Regimen	Maraviroc
Arm/Group Description	Participants randomised to this arm of the trial will remain on their usual prescribed HAART regimen.	Participants randomised to this arm will remain on their usual prescribed HAART regimen, with the addition of Maraviroc. Maraviroc will be prescribed according to the Product Information Sheet, with consideration given to background therapy. Maraviroc: Maraviroc oral tablet. Dosage: 150 mg twice daily, 300 mg twice daily, or 600 mg twice daily. Dosing will be dependent on the participant's background HAART therapy, and will be in accordance with the product information sheet.
Period Title: Overall Study
STARTED	8	9
COMPLETED	5	9
NOT COMPLETED	3	0

Baseline Characteristics

Arm/Group Title	Standard of Care HAART Regimen	Maraviroc	Total
Arm/Group Description	Participants randomised to this arm of the trial will remain on their usual prescribed HAART regimen.	Participants randomised to this arm will remain on their usual prescribed HAART regimen, with the addition of Maraviroc. Maraviroc will be prescribed according to the Product Information Sheet, with consideration given to background therapy. Maraviroc: Maraviroc oral tablet. Dosage: 150 mg twice daily, 300 mg twice daily, or 600 mg twice daily. Dosing will be dependent on the participant's background HAART therapy, and will be in accordance with the product information sheet.	Total of all reporting groups
Overall Participants	5	9	14
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	60 (9.4)	52.2 (3.7)	55 (7.1)
Sex: Female, Male (Count of Participants)
Female	0 0%	0 0%	0 0%
Male	5 100%	9 100%	14 100%
Race/Ethnicity, Customized (participants) [Number]
Caucasian	5 100%	9 100%	14 100%
Region of Enrollment (participants) [Number]
Australia	5 100%	9 100%	14 100%
Education (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	11.6 (2.3)	12.3 (2.8)	12.1 (2.6)
Premorbid intelligence quotient (IQ) (units on a scale) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [units on a scale]	104.4 (18.9)	102.2 (16.3)	103 (16.6)
Nadir cluster of differentiation 4 (CD4) (cells/mm3) [Median (Inter-Quartile Range) ]
Median (Inter-Quartile Range) [cells/mm3]	310	150	174.5
Current CD4 (cells/mm3) [Median (Inter-Quartile Range) ]
Median (Inter-Quartile Range) [cells/mm3]	980	499	625.5
HAND Status (participants) [Number]
Asymptomatic Neurocognitive Impairment (ANI)	1 20%	1 11.1%	2 14.3%
Mild Neurocognitive Disorder (MND)	2 40%	8 88.9%	10 71.4%
HIV-Associated Dementia (HAD)	2 40%	0 0%	2 14.3%

Outcome Measures

1. Primary Outcome

Title	Change in Neurocognitive Functioning
Description	Change in overall neurocognitive performance, defined as a global neurocognitive z-score, over the study time-period (baseline, 6-months, 12-months). To derive this score, 1) raw scores obtained from a 5-domain brief neurocognitive battery were converted to age-corrected z-scores (M=0, SD=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.
Time Frame	Baseline, 6-months and 12-months

Outcome Measure Data

Analysis Population Description

Modified intent-to-treat analysis. All randomized participants were included except for n=2 controls with baseline data only (1 lost to follow-up, 1 withdrew before 6-months) and n=1 control where a protocol violation was noted (randomized without conclusive evidence of neurocognitive impairment - see participant flow section).

Arm/Group Title	Standard of Care HAART Regimen	Maraviroc
Arm/Group Description	Participants randomised to this arm of the trial will remain on their usual prescribed HAART regimen.	Participants randomised to this arm will remain on their usual prescribed HAART regimen, with the addition of Maraviroc. Maraviroc will be prescribed according to the Product Information Sheet, with consideration given to background therapy. Maraviroc: Maraviroc oral tablet. Dosage: 150 mg twice daily, 300 mg twice daily, or 600 mg twice daily. Dosing will be dependent on the participant's background HAART therapy, and will be in accordance with the product information sheet.
Measure Participants	5	9
Baseline	-0.94 (0.30)	-0.81 (0.23)
6 months	-1.03 (0.30)	-0.51 (0.23)
12 months	-0.93 (0.30)	-0.56 (0.23)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Standard of Care HAART Regimen, Maraviroc
	Comments	The primary outcome was analysed using a mixed-effect regression model with arm and time as fixed linear effects, arm*time interaction as a non-linear fixed effect and participant as a random effect to account for participant attrition.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.05
	Comments	This pilot study was conducted to generate effect sizes for a potential larger investigation. The study design and small sample size had limited power to detect a statistically significant effect at p<0.05, so no p-value threshold was strictly set.
	Method	Mixed Models Analysis
	Comments	41 data points included (control n=14; maraviroc: n=27); n=1 control did not attend 12-month visit.

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Standard of Care HAART Regimen, Maraviroc
	Comments	Clinical relevance of the effect size observed at 6-months was assessed by generating Cohen's d statistic and 90% confidence interval (CI) around the estimate.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Cohen's d
	Estimated Value	0.77
	Confidence Interval	(2-Sided) 90%; -0.19 to 1.71
	Parameter Dispersion	Type: Value:
	Estimation Comments	Positive value reflects improved neurocognitive functioning in maraviroc arm compared to control arm.

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Standard of Care HAART Regimen, Maraviroc
	Comments	Clinical relevance of the effect size observed at 12-months was assessed by generating Cohen's d statistic and 90%CI around the estimate.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	0.55
	Confidence Interval	(2-Sided) 90%; -0.47 to 1.55
	Parameter Dispersion	Type: Value:
	Estimation Comments	Positive value reflects improved neurocognitive functioning in maraviroc arm compared to control arm.

2. Secondary Outcome

Title	Change in CSF Neopterin Concentration
Description	Change in concentration of the CSF neuroinflammatory marker neopterin (measured in nmol/L) from baseline to 12-months.
Time Frame	Baseline and 12-months

Outcome Measure Data

Analysis Population Description

The analysis included all randomized participants who were included in the primary analysis aside from n=1 control and n=2 maraviroc who did not provide a CSF sample at 12-months.

Arm/Group Title	Standard of Care HAART Regimen	Maraviroc
Arm/Group Description	Participants randomised to this arm of the trial will remain on their usual prescribed HAART regimen.	Participants randomised to this arm will remain on their usual prescribed HAART regimen, with the addition of Maraviroc. Maraviroc will be prescribed according to the Product Information Sheet, with consideration given to background therapy. Maraviroc: Maraviroc oral tablet. Dosage: 150 mg twice daily, 300 mg twice daily, or 600 mg twice daily. Dosing will be dependent on the participant's background HAART therapy, and will be in accordance with the product information sheet.
Measure Participants	4	7
Baseline	11.5 (3.41)	12.57 (2.57)
12-months	13.25 (3.41)	15.71 (2.57)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Standard of Care HAART Regimen, Maraviroc
	Comments	Change in CSF neopterin levels was analysed using repeated-measures ANOVA with arm, time, and arm*time interaction as fixed effects.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.82
	Comments
	Method	ANOVA
	Comments

3. Secondary Outcome

Title	Change in MRS Cerebral Metabolite Ratios in Basal Ganglia
Description	Change in major cerebral metabolites in the basal ganglia, 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 echot 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.
Time Frame	Baseline and 12 months

Outcome Measure Data

Analysis Population Description

The analysis included all randomized participants who were included in the primary analysis aside from n=1 control who did not attend MRI appointment at 12-months.

Arm/Group Title	Standard of Care HAART Regimen	Maraviroc
Arm/Group Description	Participants randomised to this arm of the trial will remain on their usual prescribed HAART regimen.	Participants randomised to this arm will remain on their usual prescribed HAART regimen, with the addition of Maraviroc. Maraviroc will be prescribed according to the Product Information Sheet, with consideration given to background therapy. Maraviroc: Maraviroc oral tablet. Dosage: 150 mg twice daily, 300 mg twice daily, or 600 mg twice daily. Dosing will be dependent on the participant's background HAART therapy, and will be in accordance with the product information sheet.
Measure Participants	4	9
NAA Baseline	3.76 (0.16)	3.96 (0.11)
NAA 12 Months	3.87 (0.16)	3.89 (0.11)
Cr Baseline	3.09 (0.16)	2.91 (0.11)
Cr 12 Months	3.24 (0.16)	3.08 (0.11)
Cho Baseline	1.42 (0.14)	1.45 (0.09)
Cho 12 Months	1.59 (0.14)	1.55 (0.09)
mIo Baseline	1.10 (0.22)	1.19 (0.15)
mIo 12 Months	0.88 (0.22)	1.07 (0.15)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Standard of Care HAART Regimen, Maraviroc
	Comments	Change in NAA/H20 levels were analysed using repeated-measures ANOVA with arm, time, and arm*time interaction as fixed effects.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.49
	Comments
	Method	ANOVA
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Standard of Care HAART Regimen, Maraviroc
	Comments	Change in Cr/H20 levels were analysed using repeated-measures ANOVA with arm, time, and arm*time interaction as fixed effects.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.94
	Comments
	Method	ANOVA
	Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Standard of Care HAART Regimen, Maraviroc
	Comments	Change in Cho/H20 levels were analysed using repeated-measures ANOVA with arm, time, and arm*time interaction as fixed effects.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.80
	Comments
	Method	ANOVA
	Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Standard of Care HAART Regimen, Maraviroc
	Comments	Change in mIo/H20 levels were analysed using repeated-measures ANOVA with arm, time, and arm*time interaction as fixed effects.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.72
	Comments
	Method	ANOVA
	Comments

4. Secondary Outcome

Title	Change in MRS Cerebral Metabolite Ratios in Frontal White Matter
Description	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 H2O as standard.
Time Frame	Baseline and 12 months

Outcome Measure Data

Analysis Population Description

The analysis included all randomized participants who were included in the primary analysis aside from n=1 control who did not attend MRI appointment at 12-months.

Arm/Group Title	Standard of Care HAART Regimen	Maraviroc
Arm/Group Description	Participants randomised to this arm of the trial will remain on their usual prescribed HAART regimen.	Participants randomised to this arm will remain on their usual prescribed HAART regimen, with the addition of Maraviroc. Maraviroc will be prescribed according to the Product Information Sheet, with consideration given to background therapy. Maraviroc: Maraviroc oral tablet. Dosage: 150 mg twice daily, 300 mg twice daily, or 600 mg twice daily. Dosing will be dependent on the participant's background HAART therapy, and will be in accordance with the product information sheet.
Measure Participants	4	9
NAA Baseline	4.32 (0.34)	4.16 (0.23)
NAA 12 Months	4.30 (0.34)	4.16 (0.23)
Cr Baseline	2.74 (0.21)	2.93 (0.14)
Cr 12 Months	2.99 (0.21)	3.05 (0.14)
Cho Baseline	2.19 (0.16)	2.13 (0.11)
Cho 12 Months	2.19 (0.16)	2.24 (0.11)
mIo Baseline	1.11 (0.15)	1.07 (0.10)
mIo 12 Months	1.15 (0.15)	1.35 (0.10)
Glx Baseline	2.16 (0.23)	2.27 (0.15)
Glx 12 Months	2.05 (0.23)	2.18 (0.15)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Standard of Care HAART Regimen, Maraviroc
	Comments	Change in NAA/H20 levels were analysed using repeated-measures ANOVA with arm, time, and arm*time interaction as fixed effects.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.95
	Comments
	Method	ANOVA
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Standard of Care HAART Regimen, Maraviroc
	Comments	Change in Cr/H20 levels were analysed using repeated-measures ANOVA with arm, time, and arm*time interaction as fixed effects.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.66
	Comments
	Method	ANOVA
	Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Standard of Care HAART Regimen, Maraviroc
	Comments	Change in Cho/H20 levels were analysed using repeated-measures ANOVA with arm, time, and arm*time interaction as fixed effects.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.56
	Comments
	Method	ANOVA
	Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Standard of Care HAART Regimen, Maraviroc
	Comments	Change in mIo/H20 levels were analysed using repeated-measures ANOVA with arm, time, and arm*time interaction as fixed effects.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.29
	Comments
	Method	ANOVA
	Comments

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	Standard of Care HAART Regimen, Maraviroc
	Comments	Change in Glx/H20 levels were analysed using repeated-measures ANOVA with arm, time, and arm*time interaction as fixed effects.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.95
	Comments
	Method	ANOVA
	Comments

Adverse Events

Time Frame	Baseline to 12-months
Arm/Group Title	Standard of Care HAART Regimen		Maraviroc
Arm/Group Description	Participants randomised to this arm of the trial will remain on their usual prescribed HAART regimen.		Participants randomised to this arm will remain on their usual prescribed HAART regimen, with the addition of Maraviroc. Maraviroc will be prescribed according to the Product Information Sheet, with consideration given to background therapy. Maraviroc: Maraviroc oral tablet. Dosage: 150 mg twice daily, 300 mg twice daily, or 600 mg twice daily. Dosing will be dependent on the participant's background HAART therapy, and will be in accordance with the product information sheet.
All Cause Mortality
	Standard of Care HAART Regimen		Maraviroc
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Standard of Care HAART Regimen		Maraviroc
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/8 (0%)		0/9 (0%)
Other (Not Including Serious) Adverse Events
	Standard of Care HAART Regimen		Maraviroc
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	2/8 (25%)		5/9 (55.6%)
Eye disorders
Blurred vision	1/8 (12.5%)	1	0/9 (0%)	0
Infections and infestations
Upper respiratory infection	0/8 (0%)	0	2/9 (22.2%)	2
Injury, poisoning and procedural complications
Fall	0/8 (0%)	0	1/9 (11.1%)	1
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Neoplasms benign, malignant and unspecified (incl cysts and polyps) - Other	0/8 (0%)	0	1/9 (11.1%)	1
Nervous system disorders
Cerebrospinal fluid leakage	1/8 (12.5%)	1	1/9 (11.1%)	1
Renal and urinary disorders
Renal calculi	1/8 (12.5%)	1	0/9 (0%)	0
Skin and subcutaneous tissue disorders
Skin infection	0/8 (0%)	0	2/9 (22.2%)	2

Limitations/Caveats

Small pilot sample size (N=17). Unrepresentative of international HAND populations. Open-label design may have contributed to loss to follow-up in controls. Modified intention-to-treat design potentially introduced bias into analyses.

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.