Flag of the European Union EU Clinical Trials Register Help

Clinical trials

The European Union Clinical Trials Register   allows you to search for protocol and results information on:
  • interventional clinical trials that were approved in the European Union (EU)/European Economic Area (EEA) under the Clinical Trials Directive 2001/20/EC
  • clinical trials conducted outside the EU/EEA that are linked to European paediatric-medicine development

  • EU/EEA interventional clinical trials approved under or transitioned to the Clinical Trial Regulation 536/2014 are publicly accessible through the
    Clinical Trials Information System (CTIS).


    The EU Clinical Trials Register currently displays   43871   clinical trials with a EudraCT protocol, of which   7290   are clinical trials conducted with subjects less than 18 years old.   The register also displays information on   18700   older paediatric trials (in scope of Article 45 of the Paediatric Regulation (EC) No 1901/2006).

    Phase 1 trials conducted solely on adults and that are not part of an agreed paediatric investigation plan (PIP) are not publicly available (see Frequently Asked Questions ).  
     
    Examples: Cancer AND drug name. Pneumonia AND sponsor name.
    How to search [pdf]
    Search Tips: Under advanced search you can use filters for Country, Age Group, Gender, Trial Phase, Trial Status, Date Range, Rare Diseases and Orphan Designation. For these items you should use the filters and not add them to your search terms in the text field.
    Advanced Search: Search tools
     

    < Back to search results

    Download PDF

    Clinical Trial Results:
    RIVER - Research In Viral Eradication of HIV Reservoirs, A two-arm (proof of concept) randomised phase II trial

    Summary
    EudraCT number
    2014-001425-32
    Trial protocol
    GB  
    Global end of trial date
    31 Mar 2023

    Results information
    Results version number
    v1(current)
    This version publication date
    12 Apr 2024
    First version publication date
    12 Apr 2024
    Other versions

    Trial information

    Close Top of page
    Trial identification
    Sponsor protocol code
    14SM2359
    Additional study identifiers
    ISRCTN number
    ISRCTN83717528
    US NCT number
    NCT02336074
    WHO universal trial number (UTN)
    U1111-1163-2579
    Other trial identifiers
    Sponsor Reference: 14SM2359
    Sponsors
    Sponsor organisation name
    Imperial College London
    Sponsor organisation address
    South Kensington, London, United Kingdom, SW7 2AZ
    Public contact
    RIVER Trial Manager, MRC Clinical Trial Unit at UCL, 0044 0207 670 4773, mrcctu.river@ucl.ac.uk
    Scientific contact
    RIVER Trial Manager, MRC Clinical Trial Unit at UCL, 0044 0207 670 4773, mrcctu.river@ucl.ac.uk
    Paediatric regulatory details
    Is trial part of an agreed paediatric investigation plan (PIP)
    No
    Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial?
    No
    Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial?
    No
    Results analysis stage
    Analysis stage
    Final
    Date of interim/final analysis
    14 Nov 2018
    Is this the analysis of the primary completion data?
    Yes
    Primary completion date
    15 Nov 2017
    Global end of trial reached?
    Yes
    Global end of trial date
    31 Mar 2023
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    To see whether in primary HIV infection, a combination of immediate combination ART (cART), immunisation and latency reactivation using the HDACi vorinostat will confer a significant reduction in the HIV reservoir when compared with cART alone.
    Protection of trial subjects
    Initiation of immediate ART for individuals with PHI is within routine practice within the UK. The vaccine strategy has been given to HIV uninfected individuals and is safe and well tolerated. There is an unknown long-term risk of toxicity following use of vorinostat. The steps taken to minimise risk and safeguard patients include: 1) very stringent inclusion and exclusion criteria to avoid enrolment of patients in which the receipt of vorinostat would cause an increased risk (theoretical or proven) of harm, for example we exclude anyone with a past history of cancer; 2) close monitoring (safety bloods and clinical assessment) during the study in order to manage and minimise side effects. Clear dose reduction and stopping rules within the protocol during vorinostat dosing; 3) exclusion of women of child bearing potential as in preclinical studies, vorinostat caused chromosomal rearrangement in the hamster ovary. 4) Long term annual follow-up for 5 years after completion of the study. 5) men with female partners must avoid getting their partners pregnant for 6 months of the intervention. Additional inclusion criteria (including safety bloods, ECG and urinalysis) have to be met before the patient is randomised at week 24, and before receipt of vorinostat at week 32 Day 3. All research staff involved in the conduct of the study at the sites are very experienced, including several in HIV vaccine studies.
    Background therapy
    -
    Evidence for comparator
    -
    Actual start date of recruitment
    08 Dec 2015
    Long term follow-up planned
    Yes
    Long term follow-up rationale
    Safety
    Long term follow-up duration
    5 Years
    Independent data monitoring committee (IDMC) involvement?
    Yes
    Population of trial subjects
    Number of subjects enrolled per country
    Country: Number of subjects enrolled
    United Kingdom: 60
    Worldwide total number of subjects
    60
    EEA total number of subjects
    0
    Number of subjects enrolled per age group
    In utero
    0
    Preterm newborn - gestational age < 37 wk
    0
    Newborns (0-27 days)
    0
    Infants and toddlers (28 days-23 months)
    0
    Children (2-11 years)
    0
    Adolescents (12-17 years)
    0
    Adults (18-64 years)
    60
    From 65 to 84 years
    0
    85 years and over
    0

    Subject disposition

    Close Top of page
    Recruitment
    Recruitment details
    82 participants were screened at 6 clinical centres in the UK of whom 63 were enrolled, 3 withdrew before randomisation, and 60 participants were randomised between 14 Jun 2016 - 11 Jul 2017: 30 control and 30 intervention.

    Pre-assignment
    Screening details
    -

    Pre-assignment period milestones
    Number of subjects started
    82 [1]
    Intermediate milestone: Number of subjects
    Enrolment: 63
    Number of subjects completed
    60

    Pre-assignment subject non-completion reasons
    Reason: Number of subjects
    Prolonged QTc interval: 5
    Reason: Number of subjects
    Concurrent comorbidity: 2
    Reason: Number of subjects
    PHI diagnosis more than 4 weeks ago: 3
    Reason: Number of subjects
    Laboratory abnormalities: 5
    Reason: Number of subjects
    Patient decision: 1
    Reason: Number of subjects
    Contraindication vorinostat + QTc interval: 1
    Reason: Number of subjects
    Contraindication for vaccines: 1
    Reason: Number of subjects
    PHI diagnosis >4 weeks ago + QTc interval: 1
    Reason: Number of subjects
    Post enrolment: withdrawn/lost: 3
    Notes
    [1] - The number of subjects reported to have started the pre-assignment period are not the same as the worldwide number enrolled in the trial. It is expected that these numbers will be the same.
    Justification: 82 individuals were screened at 6 sites in the UK of whom 63, aged 18–60 years who fulfilled all other eligibility criteria were enrolled in the study. ART was initiated at enrolment and randomisation occurred 24 weeks later, provided that the plasma HIV RNA was less than 50 copies per ml. Three of 63 participants withdrew before randomisation, and 60 were randomised. Not all patients screened have been enrolled.
    Period 1
    Period 1 title
    Main study (overall period)
    Is this the baseline period?
    Yes
    Allocation method
    Randomised - controlled
    Blinding used
    Not blinded

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    Arm A, Control
    Arm description
    Active Comparator: Control Combination Antiretroviral Therapy (cART) preferably including raltegravir prescribed at week 0 for the duration of the study up to post-randomisation week 18 (42 weeks in total)
    Arm type
    Active comparator

    Investigational medicinal product name
    Combination Antiretroviral Therapy (cART)
    Investigational medicinal product code
    Other name
    Truvada, Darunavir, Ritonavir
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    cART is prescribed at enrolment/randomisation for the duration of the study.

    Investigational medicinal product name
    Raltegravir
    Investigational medicinal product code
    Other name
    Isentress
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Raltegravir dosage: oral 400mg tablet twice per day (BID).

    Arm title
    Arm B, Intervention
    Arm description
    Experimental: Intervention Combination Antiretroviral Therapy (cART) preferably including raltegravir prescribed at week 0 for the duration of the study up to post-randomisation week 18 (42 weeks in total) Plus ChAdV63.HIVconsv prime (post-randomisation week 00) and MVA.HIVconsv boost (post randomisation week 08 day 1) vaccines; followed by a 28-day course of vorinostat (10 doses in total).
    Arm type
    Experimental

    Investigational medicinal product name
    Combination Antiretroviral Therapy (cART)
    Investigational medicinal product code
    Other name
    Truvada, Darunavir, Ritonavir
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    cART is prescribed at enrolment/randomisation for the duration of the study.

    Investigational medicinal product name
    Raltegravir
    Investigational medicinal product code
    Other name
    Isentress
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Raltegravir dosage: oral 400mg tablet twice per day (BID).

    Investigational medicinal product name
    Vorinostat
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Capsule
    Routes of administration
    Oral use
    Dosage and administration details
    Vorinostat (suberoylanilide hydroxamic acid abbreviated to SAHA) inhibits the histone deacetylases HDAC1, HDAC2, HDAC3 (Class I) and HDAC6 (Class II). Vorinostat is supplied as capsules containing 100mg vorinostat and the following inactive ingredients: microcrystalline cellulose, sodium croscarmellose and magnesium stearate. Dosage: oral 400mg every third day from post randomisation week 8 day 3 (PR08-3) to week 12 day 2 (PR12-2) inclusive. 10 doses in total. Administration: Vorinostat is administered orally with food. Participants should drink at least 2L fluid/day (on drug dosing days) to prevent dehydration and must report any excessive vomiting or diarrhoea; signs or symptoms of deep vein thrombosis (swelling and pain in a limb, shortness of breath, cough, pleuritic chest pain); unusual bleeding and seek medical attention.

    Investigational medicinal product name
    ChAdV63.HIVconsv (ChAd)
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Injection
    Routes of administration
    Intramuscular use
    Dosage and administration details
    Dosage: 5x10^10 vp Administration: This dose is obtained by injecting 0.37ml of the vaccine at 1.35x10^11 vp/ml without dilution. This prime vaccination is administered intramuscularly (IM) into the deltoid muscle of the non-dominant arm within 1 week of randomisation at visit post randomisation week 00 (PR00).

    Investigational medicinal product name
    MVA.HIVconsv (MVA)
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Injection
    Routes of administration
    Intramuscular use
    Dosage and administration details
    Dosage: 2x10^8 pfu Administration: This dose is obtained by injecting 0.23 ml of the vaccine IM at 8.6x10^8 pfu/ml without dilution. This boost vaccination is administered intramuscularly (IM) into the deltoid muscle of the non-dominant arm at post-randomisation week 08 Day 1 (2 prior to start of vorinostat)

    Number of subjects in period 1
    Arm A, Control Arm B, Intervention
    Started
    30
    30
    Completed
    30
    30

    Baseline characteristics

    Close Top of page
    Baseline characteristics reporting groups
    Reporting group title
    Arm A, Control
    Reporting group description
    Active Comparator: Control Combination Antiretroviral Therapy (cART) preferably including raltegravir prescribed at week 0 for the duration of the study up to post-randomisation week 18 (42 weeks in total)

    Reporting group title
    Arm B, Intervention
    Reporting group description
    Experimental: Intervention Combination Antiretroviral Therapy (cART) preferably including raltegravir prescribed at week 0 for the duration of the study up to post-randomisation week 18 (42 weeks in total) Plus ChAdV63.HIVconsv prime (post-randomisation week 00) and MVA.HIVconsv boost (post randomisation week 08 day 1) vaccines; followed by a 28-day course of vorinostat (10 doses in total).

    Reporting group values
    Arm A, Control Arm B, Intervention Total
    Number of subjects
    30 30 60
    Age categorical
    Aged ≥18 to ≤60 years old
    Units: Subjects
        In utero
    0 0 0
        Preterm newborn infants (gestational age < 37 wks)
    0 0 0
        Newborns (0-27 days)
    0 0 0
        Infants and toddlers (28 days-23 months)
    0 0 0
        Children (2-11 years)
    0 0 0
        Adolescents (12-17 years)
    0 0 0
        Adults (18-64 years)
    30 30 60
        From 65-84 years
    0 0 0
        85 years and over
    0 0 0
    Age continuous
    Units: years
        median (inter-quartile range (Q1-Q3))
    31 (30 to 38) 35 (28 to 44) -
    Gender categorical
    All 60 participants were male
    Units: Subjects
        Female
    0 0 0
        Male
    30 30 60
    Stratum
    Units: Subjects
        Stratum 1
    26 26 52
        Stratum 2
    4 4 8
    Ethnicity
    Units: Subjects
        White
    16 26 42
        South Asian
    0 1 1
        South East Asian
    1 0 1
        Hispanic/Latino
    3 2 5
        Black Caribbean/American
    2 0 2
        Black African
    2 0 2
        Mixed ethnic group
    5 1 6
        Other
    1 0 1
    Mode of HIV infection
    Units: Subjects
        MSM
    26 29 55
        MSW
    1 1 2
        Unknown
    1 0 1
        MSM+IDU
    2 0 2
    HIV RNA
    Units: Subjects
        <50 copies/ml
    29 30 59
        50 - <200 copies/ml
    1 0 1
    Weeks since PHI diagnosis
    Units: Subjects
        ≤1 week
    1 0 1
        >1 - 2 weeks
    3 3 6
        >2 - 3 weeks
    7 7 14
        >3 - 4 weeks
    15 16 31
        >4 weeks
    4 4 8
    CD4 cell count
    Units: cells/mm3
        median (inter-quartile range (Q1-Q3))
    694 (561 to 844) 710 (579 to 759) -
    CD4/CD8 ratio
    Units: ratio
        median (inter-quartile range (Q1-Q3))
    1.09 (0.77 to 1.42) 1.07 (0.91 to 1.46) -
    eGFR
    Units: mL/min/1.73 m²
        median (inter-quartile range (Q1-Q3))
    106 (99 to 119) 111 (105 to 120) -
    Time since PHI diagnosis
    Units: weeks
        median (inter-quartile range (Q1-Q3))
    28 (27 to 41) 28 (27 to 34) -

    End points

    Close Top of page
    End points reporting groups
    Reporting group title
    Arm A, Control
    Reporting group description
    Active Comparator: Control Combination Antiretroviral Therapy (cART) preferably including raltegravir prescribed at week 0 for the duration of the study up to post-randomisation week 18 (42 weeks in total)

    Reporting group title
    Arm B, Intervention
    Reporting group description
    Experimental: Intervention Combination Antiretroviral Therapy (cART) preferably including raltegravir prescribed at week 0 for the duration of the study up to post-randomisation week 18 (42 weeks in total) Plus ChAdV63.HIVconsv prime (post-randomisation week 00) and MVA.HIVconsv boost (post randomisation week 08 day 1) vaccines; followed by a 28-day course of vorinostat (10 doses in total).

    Primary: Total HIV DNA from CD4 T-cells averaged across post randomisation weeks 16 and 18

    Close Top of page
    End point title
    Total HIV DNA from CD4 T-cells averaged across post randomisation weeks 16 and 18
    End point description
    The primary endpoint was total HIV-DNA averaged across post-randomisation weeks 16 and 18. It was analysed on a log10-scale. Treatment arms were compared in terms of absolute total HIV DNA levels at post-randomisation weeks 16 and 18 adjusted for the baseline (i.e. randomisation) level and by stratum using analysis of covariance. If either the PR week 16 result or the PR week 18 result were entirely missing but not both, the primary endpoint consisted of the single available result. If total HIV DNA was missing at both PR-16 or PR-18, or at baseline, an imputation method was used to estimate missing values. Predictors included stratum, total HIV-DNA from previous time-points and other factors associated with total HIV DNA.” Baseline results were missing in 2 participants. Results were imputed using stratum and mean total HIV-DNA from PR week 16 and 18. Therefore, the primary analysis of the primary endpoint included all 60 randomised participants.
    End point type
    Primary
    End point timeframe
    Post randomisation weeks 16 and 18
    End point values
    Arm A, Control Arm B, Intervention
    Number of subjects analysed
    30
    30
    Units: HIV-DNA copies/million CD4+T cells
        log mean (standard deviation)
    2.95 ( 0.50 )
    3.06 ( 0.49 )
    Statistical analysis title
    Difference in total HIV-DNA
    Statistical analysis description
    Difference: Intervention minus Control. Analysis using linear regression on log10 scale adjusted for baseline value and stratum
    Comparison groups
    Arm A, Control v Arm B, Intervention
    Number of subjects included in analysis
    60
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.256
    Method
    Regression, Linear
    Parameter type
    Mean difference (final values)
    Point estimate
    0.041
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -0.031
         upper limit
    0.113
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.036

    Secondary: Integrated HIV DNA from CD4 T-cells averaged across post randomisation weeks 16 and 18

    Close Top of page
    End point title
    Integrated HIV DNA from CD4 T-cells averaged across post randomisation weeks 16 and 18
    End point description
    End point type
    Secondary
    End point timeframe
    Post randomisation weeks 16 and 18
    End point values
    Arm A, Control Arm B, Intervention
    Number of subjects analysed
    29
    23
    Units: copies per 10⁶ CD4+ T cells
        log mean (standard deviation)
    2.79 ( 0.51 )
    2.83 ( 0.45 )
    Statistical analysis title
    Difference
    Statistical analysis description
    Difference: Intervention minus Control. Derived from linear regression adjusted for baseline value and stratum on log10 scale
    Comparison groups
    Arm A, Control v Arm B, Intervention
    Number of subjects included in analysis
    52
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.603
    Method
    Regression, Linear
    Parameter type
    Mean difference (final values)
    Point estimate
    0.05
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -0.15
         upper limit
    0.25
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.1

    Secondary: Viral outgrowth (replication competence)

    Close Top of page
    End point title
    Viral outgrowth (replication competence)
    End point description
    End point type
    Secondary
    End point timeframe
    Post randomisation week 16
    End point values
    Arm A, Control Arm B, Intervention
    Number of subjects analysed
    29
    27
    Units: undetectable viral outgrowth
    12
    6
    Statistical analysis title
    Difference
    Statistical analysis description
    Logistic regression, adjusted for stratum & baseline undetectable and imputed missing baseline results (imputed separately for each arm using multiple imputation based on stratum and PR week 16 results). Control in the model: Arm A
    Comparison groups
    Arm A, Control v Arm B, Intervention
    Number of subjects included in analysis
    56
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.145
    Method
    Regression, Logistic
    Parameter type
    Odds ratio (OR)
    Point estimate
    0.41
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    0.13
         upper limit
    1.35
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.25

    Secondary: HIV RNA from single copy assay

    Close Top of page
    End point title
    HIV RNA from single copy assay
    End point description
    End point type
    Secondary
    End point timeframe
    Post randomisation week 18
    End point values
    Arm A, Control Arm B, Intervention
    Number of subjects analysed
    26
    29
    Units: copies/mL
        median (inter-quartile range (Q1-Q3))
    6 (1 to 20)
    6 (1 to 14)
    Statistical analysis title
    Difference
    Comparison groups
    Arm A, Control v Arm B, Intervention
    Number of subjects included in analysis
    55
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.81
    Method
    Wilcoxon (Mann-Whitney)
    Confidence interval

    Secondary: HIV cell-associated unspliced RNA

    Close Top of page
    End point title
    HIV cell-associated unspliced RNA
    End point description
    End point type
    Secondary
    End point timeframe
    Post randomisation week 16 and 18, average
    End point values
    Arm A, Control Arm B, Intervention
    Number of subjects analysed
    27
    23
    Units: copies per ng
        median (inter-quartile range (Q1-Q3))
    0.12 (0.02 to 0.90)
    0.29 (0.01 to 0.96)
    Statistical analysis title
    Difference in HIV cell associated RNA
    Statistical analysis description
    Median regression of post-randomisation weeks 16 & 18 average, with bootstrapped standard error (Stata command bsqreg), adjusted for baseline value and stratum, to estimate the difference Intervention minus Control.
    Comparison groups
    Arm A, Control v Arm B, Intervention
    Number of subjects included in analysis
    50
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.83
    Method
    Median regression
    Parameter type
    Median difference (final values)
    Point estimate
    0.02
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -0.19
         upper limit
    0.24
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.11

    Secondary: HIV-specific CD4+ T cells positive for CD154

    Close Top of page
    End point title
    HIV-specific CD4+ T cells positive for CD154
    End point description
    End point type
    Secondary
    End point timeframe
    Post randomisation week 9
    End point values
    Arm A, Control Arm B, Intervention
    Number of subjects analysed
    27
    30
    Units: proportion of cells
        median (inter-quartile range (Q1-Q3))
    0.021 (0.001 to 0.037)
    0.141 (0.065 to 0.256)
    Statistical analysis title
    Difference
    Comparison groups
    Arm A, Control v Arm B, Intervention
    Number of subjects included in analysis
    57
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    < 0.001
    Method
    Wilcoxon (Mann-Whitney)
    Confidence interval

    Secondary: HIV-specific CD4+ T cells positive for CD154

    Close Top of page
    End point title
    HIV-specific CD4+ T cells positive for CD154
    End point description
    End point type
    Secondary
    End point timeframe
    Post randomisation week 12
    End point values
    Arm A, Control Arm B, Intervention
    Number of subjects analysed
    27
    30
    Units: proportion of cells
        median (inter-quartile range (Q1-Q3))
    0.025 (0.011 to 0.049)
    0.174 (0.118 to 0.257)
    Statistical analysis title
    Difference
    Comparison groups
    Arm A, Control v Arm B, Intervention
    Number of subjects included in analysis
    57
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    < 0.001
    Method
    Wilcoxon (Mann-Whitney)
    Confidence interval

    Secondary: HIV-specific CD4+ T cells positive for IFNγ

    Close Top of page
    End point title
    HIV-specific CD4+ T cells positive for IFNγ
    End point description
    End point type
    Secondary
    End point timeframe
    Post randomisation week 9
    End point values
    Arm A, Control Arm B, Intervention
    Number of subjects analysed
    27
    30
    Units: proportion of cells
        median (inter-quartile range (Q1-Q3))
    0.007 (0.000 to 0.042)
    0.102 (0.051 to 0.235)
    Statistical analysis title
    Difference
    Comparison groups
    Arm A, Control v Arm B, Intervention
    Number of subjects included in analysis
    57
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    < 0.001
    Method
    Wilcoxon (Mann-Whitney)
    Confidence interval

    Secondary: HIV-specific CD4+ T cells positive for IFNγ

    Close Top of page
    End point title
    HIV-specific CD4+ T cells positive for IFNγ
    End point description
    End point type
    Secondary
    End point timeframe
    Post randomisation week 12
    End point values
    Arm A, Control Arm B, Intervention
    Number of subjects analysed
    27
    30
    Units: proportion of cells
        median (inter-quartile range (Q1-Q3))
    0.034 (0.007 to 0.061)
    0.181 (0.070 to 0.266)
    Statistical analysis title
    Difference
    Comparison groups
    Arm A, Control v Arm B, Intervention
    Number of subjects included in analysis
    57
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    < 0.001
    Method
    Wilcoxon (Mann-Whitney)
    Confidence interval

    Secondary: HIV-specific CD4+ T cells positive for IL2

    Close Top of page
    End point title
    HIV-specific CD4+ T cells positive for IL2
    End point description
    End point type
    Secondary
    End point timeframe
    Post randomisation week 9
    End point values
    Arm A, Control Arm B, Intervention
    Number of subjects analysed
    27
    30
    Units: proportion of cells
        median (inter-quartile range (Q1-Q3))
    0.006 (0.000 to 0.024)
    0.073 (0.022 to 0.132)
    Statistical analysis title
    Difference
    Comparison groups
    Arm A, Control v Arm B, Intervention
    Number of subjects included in analysis
    57
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    < 0.001
    Method
    Wilcoxon (Mann-Whitney)
    Confidence interval

    Secondary: HIV-specific CD4+ T cells positive for IL2

    Close Top of page
    End point title
    HIV-specific CD4+ T cells positive for IL2
    End point description
    End point type
    Secondary
    End point timeframe
    Post randomisation week 12
    End point values
    Arm A, Control Arm B, Intervention
    Number of subjects analysed
    27
    30
    Units: proportion of cells
        median (inter-quartile range (Q1-Q3))
    0.008 (0.000 to 0.019)
    0.118 (0.069 to 0.158)
    Statistical analysis title
    Difference
    Comparison groups
    Arm A, Control v Arm B, Intervention
    Number of subjects included in analysis
    57
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    < 0.001
    Method
    Wilcoxon (Mann-Whitney)
    Confidence interval

    Secondary: HIV-specific CD4+ T cells positive for TNFα

    Close Top of page
    End point title
    HIV-specific CD4+ T cells positive for TNFα
    End point description
    End point type
    Secondary
    End point timeframe
    Post randomisation week 9
    End point values
    Arm A, Control Arm B, Intervention
    Number of subjects analysed
    27
    30
    Units: proportion of cells
        median (inter-quartile range (Q1-Q3))
    0.020 (0.002 to 0.051)
    0.183 (0.104 to 0.274)
    Statistical analysis title
    Difference
    Comparison groups
    Arm A, Control v Arm B, Intervention
    Number of subjects included in analysis
    57
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    < 0.001
    Method
    Wilcoxon (Mann-Whitney)
    Confidence interval

    Secondary: HIV-specific CD4+ T cells positive for TNFα

    Close Top of page
    End point title
    HIV-specific CD4+ T cells positive for TNFα
    End point description
    End point type
    Secondary
    End point timeframe
    Post randomisation week 12
    End point values
    Arm A, Control Arm B, Intervention
    Number of subjects analysed
    27
    30
    Units: proportion of cells
        median (inter-quartile range (Q1-Q3))
    0.028 (0.011 to 0.059)
    0.175 (0.128 to 0.300)
    Statistical analysis title
    Difference
    Comparison groups
    Arm A, Control v Arm B, Intervention
    Number of subjects included in analysis
    57
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    < 0.001
    Method
    Wilcoxon (Mann-Whitney)
    Confidence interval

    Secondary: HIV-specific CD8+ T cells positive for CD154

    Close Top of page
    End point title
    HIV-specific CD8+ T cells positive for CD154
    End point description
    End point type
    Secondary
    End point timeframe
    Post randomisation week 9
    End point values
    Arm A, Control Arm B, Intervention
    Number of subjects analysed
    27
    30
    Units: proportion of cells
        median (inter-quartile range (Q1-Q3))
    0.008 (0.000 to 0.017)
    0.011 (0.006 to 0.036)
    Statistical analysis title
    Difference
    Comparison groups
    Arm A, Control v Arm B, Intervention
    Number of subjects included in analysis
    57
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.089
    Method
    Wilcoxon (Mann-Whitney)
    Confidence interval

    Secondary: HIV-specific CD8+ T cells positive for CD154

    Close Top of page
    End point title
    HIV-specific CD8+ T cells positive for CD154
    End point description
    End point type
    Secondary
    End point timeframe
    Post randomisation week 12
    End point values
    Arm A, Control Arm B, Intervention
    Number of subjects analysed
    27
    30
    Units: proportion of cells
        median (inter-quartile range (Q1-Q3))
    0.004 (0.000 to 0.010)
    0.009 (0.002 to 0.040)
    Statistical analysis title
    Difference
    Comparison groups
    Arm A, Control v Arm B, Intervention
    Number of subjects included in analysis
    57
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.12
    Method
    Wilcoxon (Mann-Whitney)
    Confidence interval

    Secondary: HIV-specific CD8+ T cells positive for IFNγ

    Close Top of page
    End point title
    HIV-specific CD8+ T cells positive for IFNγ
    End point description
    End point type
    Secondary
    End point timeframe
    Post randomisation week 9
    End point values
    Arm A, Control Arm B, Intervention
    Number of subjects analysed
    27
    30
    Units: proportion of cells
        median (inter-quartile range (Q1-Q3))
    0.114 (0.036 to 0.307)
    0.320 (0.195 to 0.942)
    Statistical analysis title
    Difference
    Comparison groups
    Arm A, Control v Arm B, Intervention
    Number of subjects included in analysis
    57
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.002
    Method
    Wilcoxon (Mann-Whitney)
    Confidence interval

    Secondary: HIV-specific CD8+ T cells positive for IFNγ

    Close Top of page
    End point title
    HIV-specific CD8+ T cells positive for IFNγ
    End point description
    End point type
    Secondary
    End point timeframe
    Post randomisation week 12
    End point values
    Arm A, Control Arm B, Intervention
    Number of subjects analysed
    27
    30
    Units: proportion of cells
        median (inter-quartile range (Q1-Q3))
    0.170 (0.057 to 0.279)
    0.309 (0.177 to 1.061)
    Statistical analysis title
    Difference
    Comparison groups
    Arm A, Control v Arm B, Intervention
    Number of subjects included in analysis
    57
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.004
    Method
    Wilcoxon (Mann-Whitney)
    Confidence interval

    Secondary: HIV-specific CD8+ T cells positive for IL2

    Close Top of page
    End point title
    HIV-specific CD8+ T cells positive for IL2
    End point description
    End point type
    Secondary
    End point timeframe
    Post randomisation week 9
    End point values
    Arm A, Control Arm B, Intervention
    Number of subjects analysed
    27
    30
    Units: proportion of cells
        median (inter-quartile range (Q1-Q3))
    0.004 (0.000 to 0.015)
    0.065 (0.010 to 0.190)
    Statistical analysis title
    Difference
    Comparison groups
    Arm A, Control v Arm B, Intervention
    Number of subjects included in analysis
    57
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.001
    Method
    Wilcoxon (Mann-Whitney)
    Confidence interval

    Secondary: HIV-specific CD8+ T cells positive for IL2

    Close Top of page
    End point title
    HIV-specific CD8+ T cells positive for IL2
    End point description
    End point type
    Secondary
    End point timeframe
    Post randomisation week 12
    End point values
    Arm A, Control Arm B, Intervention
    Number of subjects analysed
    27
    30
    Units: proportion of cells
        median (inter-quartile range (Q1-Q3))
    0.010 (0.000 to 0.032)
    0.017 (0.000 to 0.105)
    Statistical analysis title
    Difference
    Comparison groups
    Arm A, Control v Arm B, Intervention
    Number of subjects included in analysis
    57
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.45
    Method
    Wilcoxon (Mann-Whitney)
    Confidence interval

    Secondary: HIV-specific CD8+ T cells positive for TNFα

    Close Top of page
    End point title
    HIV-specific CD8+ T cells positive for TNFα
    End point description
    End point type
    Secondary
    End point timeframe
    Post randomisation week 9
    End point values
    Arm A, Control Arm B, Intervention
    Number of subjects analysed
    27
    30
    Units: proportion of cells
        median (inter-quartile range (Q1-Q3))
    0.104 (0.033 to 0.207)
    0.240 (0.102 to 0.645)
    Statistical analysis title
    Difference
    Comparison groups
    Arm A, Control v Arm B, Intervention
    Number of subjects included in analysis
    57
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.015
    Method
    Wilcoxon (Mann-Whitney)
    Confidence interval

    Secondary: HIV-specific CD8+ T cells positive for TNFα

    Close Top of page
    End point title
    HIV-specific CD8+ T cells positive for TNFα
    End point description
    End point type
    Secondary
    End point timeframe
    Post randomisation week 12
    End point values
    Arm A, Control Arm B, Intervention
    Number of subjects analysed
    27
    30
    Units: proportion of cells
        median (inter-quartile range (Q1-Q3))
    0.139 (0.018 to 0.255)
    0.232 (0.102 to 0.585)
    Statistical analysis title
    Difference
    Comparison groups
    Arm A, Control v Arm B, Intervention
    Number of subjects included in analysis
    57
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.013
    Method
    Wilcoxon (Mann-Whitney)
    Confidence interval

    Secondary: CD8+ T Cell antiviral activity (viral inhibition)

    Close Top of page
    End point title
    CD8+ T Cell antiviral activity (viral inhibition)
    End point description
    CD8+ T cell antiviral suppressive activity will be expressed as percentage inhibition and determined as follows: [(fraction of p24 + cells in CD4 + T cells cultured alone)– (fraction of p24 + in CD4+ T cells cultured with CD8+ cells)]/(fraction of p24 + cells in CD4 +T cells cultured alone) × 100. A CD4:CD8 ratio of 10:1 was used for this analysis.
    End point type
    Secondary
    End point timeframe
    Post randomisation week 9
    End point values
    Arm A, Control Arm B, Intervention
    Number of subjects analysed
    24
    25
    Units: % inhibition
        median (inter-quartile range (Q1-Q3))
    41 (11 to 86)
    75 (22 to 95)
    Statistical analysis title
    Difference in change from randomisation
    Statistical analysis description
    Linear regression, adjusted for baseline result and stratum Difference between arms defined as Intervention minus Control
    Comparison groups
    Arm B, Intervention v Arm A, Control
    Number of subjects included in analysis
    49
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.104
    Method
    Regression, Linear
    Parameter type
    Mean difference (final values)
    Point estimate
    14.29
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -3.06
         upper limit
    31.64
    Variability estimate
    Standard error of the mean
    Dispersion value
    8.61

    Secondary: CD8+ T Cell antiviral activity (viral inhibition)

    Close Top of page
    End point title
    CD8+ T Cell antiviral activity (viral inhibition)
    End point description
    CD8+ T cell antiviral suppressive activity will be expressed as percentage inhibition and determined as follows: [(fraction of p24 + cells in CD4 + T cells cultured alone)– (fraction of p24 + in CD4+ T cells cultured with CD8+ cells)]/(fraction of p24 + cells in CD4 +T cells cultured alone) × 100. A CD4:CD8 ratio of 10:1 was used for this analysis.
    End point type
    Secondary
    End point timeframe
    Post randomisation week 12
    End point values
    Arm A, Control Arm B, Intervention
    Number of subjects analysed
    24
    26
    Units: % inhibition
        median (inter-quartile range (Q1-Q3))
    21 (4 to 65)
    71 (14 to 92)
    Statistical analysis title
    Difference in change from randomisation
    Statistical analysis description
    linear regression, adjusted for baseline result and stratum. Difference between arms defined as Intervention minus Control
    Comparison groups
    Arm A, Control v Arm B, Intervention
    Number of subjects included in analysis
    50
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.026
    Method
    Regression, Linear
    Parameter type
    Mean difference (final values)
    Point estimate
    19.75
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    2.42
         upper limit
    37.08
    Variability estimate
    Standard error of the mean
    Dispersion value
    8.61

    Secondary: CD4/CD8 ratio

    Close Top of page
    End point title
    CD4/CD8 ratio
    End point description
    End point type
    Secondary
    End point timeframe
    Post randomisation week 8
    End point values
    Arm A, Control Arm B, Intervention
    Number of subjects analysed
    27
    28
    Units: ratio
        median (inter-quartile range (Q1-Q3))
    1.08 (0.84 to 1.41)
    1.16 (0.82 to 1.42)
    Statistical analysis title
    Difference
    Comparison groups
    Arm A, Control v Arm B, Intervention
    Number of subjects included in analysis
    55
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.54
    Method
    t-test, 2-sided
    Confidence interval

    Secondary: CD4/CD8 ratio

    Close Top of page
    End point title
    CD4/CD8 ratio
    End point description
    End point type
    Secondary
    End point timeframe
    Post randomisation week 16
    End point values
    Arm A, Control Arm B, Intervention
    Number of subjects analysed
    30
    30
    Units: ratio
        median (inter-quartile range (Q1-Q3))
    1.18 (0.89 to 1.53)
    1.27 (0.93 to 1.50)
    Statistical analysis title
    Difference
    Comparison groups
    Arm A, Control v Arm B, Intervention
    Number of subjects included in analysis
    60
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.82
    Method
    t-test, 2-sided
    Confidence interval

    Adverse events

    Close Top of page
    Adverse events information
    Timeframe for reporting adverse events
    Main trial: randomisation to post randomisation week 18.
    Assessment type
    Non-systematic
    Dictionary used for adverse event reporting
    Dictionary name
    MedDRA
    Dictionary version
    19
    Reporting groups
    Reporting group title
    Control
    Reporting group description
    -

    Reporting group title
    Intervention
    Reporting group description
    -

    Serious adverse events
    Control Intervention
    Total subjects affected by serious adverse events
         subjects affected / exposed
    0 / 30 (0.00%)
    1 / 30 (3.33%)
         number of deaths (all causes)
    0
    0
         number of deaths resulting from adverse events
    Nervous system disorders
    Syncope vasovagal
         subjects affected / exposed
    0 / 30 (0.00%)
    1 / 30 (3.33%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 0%
    Non-serious adverse events
    Control Intervention
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    22 / 30 (73.33%)
    29 / 30 (96.67%)
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Skin Tags
         subjects affected / exposed
    0 / 30 (0.00%)
    1 / 30 (3.33%)
         occurrences all number
    0
    1
    General disorders and administration site conditions
    Administration Site Rash
         subjects affected / exposed
    0 / 30 (0.00%)
    1 / 30 (3.33%)
         occurrences all number
    0
    1
    Excessive Thirst
         subjects affected / exposed
    0 / 30 (0.00%)
    1 / 30 (3.33%)
         occurrences all number
    0
    1
    Fatigue
         subjects affected / exposed
    0 / 30 (0.00%)
    11 / 30 (36.67%)
         occurrences all number
    0
    11
    Flu-Like Symptoms
         subjects affected / exposed
    0 / 30 (0.00%)
    2 / 30 (6.67%)
         occurrences all number
    0
    2
    General Malaise
         subjects affected / exposed
    0 / 30 (0.00%)
    1 / 30 (3.33%)
         occurrences all number
    0
    1
    Injection Site Muscle Pain
         subjects affected / exposed
    0 / 30 (0.00%)
    1 / 30 (3.33%)
         occurrences all number
    0
    1
    Injection Site Pain
         subjects affected / exposed
    0 / 30 (0.00%)
    2 / 30 (6.67%)
         occurrences all number
    0
    2
    Night Sweats
         subjects affected / exposed
    1 / 30 (3.33%)
    0 / 30 (0.00%)
         occurrences all number
    1
    0
    Tiredness
         subjects affected / exposed
    0 / 30 (0.00%)
    1 / 30 (3.33%)
         occurrences all number
    0
    1
    Vaccination Site Induration
         subjects affected / exposed
    0 / 30 (0.00%)
    1 / 30 (3.33%)
         occurrences all number
    0
    1
    Vaccination Site Pain
         subjects affected / exposed
    0 / 30 (0.00%)
    5 / 30 (16.67%)
         occurrences all number
    0
    6
    Respiratory, thoracic and mediastinal disorders
    Cough
         subjects affected / exposed
    0 / 30 (0.00%)
    2 / 30 (6.67%)
         occurrences all number
    0
    2
    Hay Fever
         subjects affected / exposed
    1 / 30 (3.33%)
    1 / 30 (3.33%)
         occurrences all number
    1
    1
    Nasal Congestion
         subjects affected / exposed
    0 / 30 (0.00%)
    1 / 30 (3.33%)
         occurrences all number
    0
    1
    Sore Throat
         subjects affected / exposed
    1 / 30 (3.33%)
    1 / 30 (3.33%)
         occurrences all number
    1
    1
    Psychiatric disorders
    Anxiety
         subjects affected / exposed
    0 / 30 (0.00%)
    2 / 30 (6.67%)
         occurrences all number
    0
    2
    Low Mood
         subjects affected / exposed
    2 / 30 (6.67%)
    1 / 30 (3.33%)
         occurrences all number
    2
    1
    Panic Attack
         subjects affected / exposed
    0 / 30 (0.00%)
    1 / 30 (3.33%)
         occurrences all number
    0
    1
    Vivid Dreams
         subjects affected / exposed
    0 / 30 (0.00%)
    1 / 30 (3.33%)
         occurrences all number
    0
    1
    Injury, poisoning and procedural complications
    Head Injury
         subjects affected / exposed
    1 / 30 (3.33%)
    0 / 30 (0.00%)
         occurrences all number
    1
    0
    Insect Bite Nos
         subjects affected / exposed
    0 / 30 (0.00%)
    1 / 30 (3.33%)
         occurrences all number
    0
    1
    Soft Tissue Injury
         subjects affected / exposed
    1 / 30 (3.33%)
    0 / 30 (0.00%)
         occurrences all number
    1
    0
    Wrist Injury
         subjects affected / exposed
    1 / 30 (3.33%)
    0 / 30 (0.00%)
         occurrences all number
    1
    0
    Cardiac disorders
    Atrioventricular Block
         subjects affected / exposed
    0 / 30 (0.00%)
    1 / 30 (3.33%)
         occurrences all number
    0
    1
    Nervous system disorders
    Dizziness
         subjects affected / exposed
    0 / 30 (0.00%)
    1 / 30 (3.33%)
         occurrences all number
    0
    1
    Forgetfulness
         subjects affected / exposed
    1 / 30 (3.33%)
    0 / 30 (0.00%)
         occurrences all number
    1
    0
    Headache
         subjects affected / exposed
    0 / 30 (0.00%)
    4 / 30 (13.33%)
         occurrences all number
    0
    4
    Light Headedness
         subjects affected / exposed
    0 / 30 (0.00%)
    1 / 30 (3.33%)
         occurrences all number
    0
    1
    Sleepiness
         subjects affected / exposed
    0 / 30 (0.00%)
    2 / 30 (6.67%)
         occurrences all number
    0
    3
    Gastrointestinal disorders
    Acute Gastroenteritis
         subjects affected / exposed
    1 / 30 (3.33%)
    0 / 30 (0.00%)
         occurrences all number
    1
    0
    Anal Fissure
         subjects affected / exposed
    1 / 30 (3.33%)
    0 / 30 (0.00%)
         occurrences all number
    1
    0
    Anal Warts
         subjects affected / exposed
    1 / 30 (3.33%)
    0 / 30 (0.00%)
         occurrences all number
    1
    0
    Constipation
         subjects affected / exposed
    0 / 30 (0.00%)
    1 / 30 (3.33%)
         occurrences all number
    0
    1
    Diarrhoea
         subjects affected / exposed
    3 / 30 (10.00%)
    7 / 30 (23.33%)
         occurrences all number
    3
    9
    Dry Mouth
         subjects affected / exposed
    0 / 30 (0.00%)
    3 / 30 (10.00%)
         occurrences all number
    0
    3
    Epigastric Pain
         subjects affected / exposed
    1 / 30 (3.33%)
    0 / 30 (0.00%)
         occurrences all number
    1
    0
    Gastroenteritis
         subjects affected / exposed
    1 / 30 (3.33%)
    0 / 30 (0.00%)
         occurrences all number
    1
    0
    Heartburn
         subjects affected / exposed
    1 / 30 (3.33%)
    0 / 30 (0.00%)
         occurrences all number
    1
    0
    Loose Stools
         subjects affected / exposed
    1 / 30 (3.33%)
    1 / 30 (3.33%)
         occurrences all number
    1
    1
    Nausea
         subjects affected / exposed
    0 / 30 (0.00%)
    5 / 30 (16.67%)
         occurrences all number
    0
    5
    Proctitis
         subjects affected / exposed
    1 / 30 (3.33%)
    0 / 30 (0.00%)
         occurrences all number
    1
    0
    Rectal Bleeding
         subjects affected / exposed
    1 / 30 (3.33%)
    0 / 30 (0.00%)
         occurrences all number
    1
    0
    Vomiting
         subjects affected / exposed
    0 / 30 (0.00%)
    1 / 30 (3.33%)
         occurrences all number
    0
    4
    Skin and subcutaneous tissue disorders
    Eczema
         subjects affected / exposed
    0 / 30 (0.00%)
    1 / 30 (3.33%)
         occurrences all number
    0
    2
    Epidermal Cyst
         subjects affected / exposed
    1 / 30 (3.33%)
    0 / 30 (0.00%)
         occurrences all number
    1
    0
    Erythematous Rash
         subjects affected / exposed
    0 / 30 (0.00%)
    2 / 30 (6.67%)
         occurrences all number
    0
    2
    Folliculitis
         subjects affected / exposed
    0 / 30 (0.00%)
    1 / 30 (3.33%)
         occurrences all number
    0
    1
    Foot Callus
         subjects affected / exposed
    1 / 30 (3.33%)
    0 / 30 (0.00%)
         occurrences all number
    1
    0
    Itchy Rash
         subjects affected / exposed
    0 / 30 (0.00%)
    1 / 30 (3.33%)
         occurrences all number
    0
    1
    Night Sweats
         subjects affected / exposed
    0 / 30 (0.00%)
    1 / 30 (3.33%)
         occurrences all number
    0
    1
    Seborrhoeic Dermatitis
         subjects affected / exposed
    1 / 30 (3.33%)
    0 / 30 (0.00%)
         occurrences all number
    1
    0
    Skin Rash
         subjects affected / exposed
    0 / 30 (0.00%)
    1 / 30 (3.33%)
         occurrences all number
    0
    1
    Tinea Corporis
         subjects affected / exposed
    0 / 30 (0.00%)
    1 / 30 (3.33%)
         occurrences all number
    0
    1
    Renal and urinary disorders
    Haematuria
         subjects affected / exposed
    1 / 30 (3.33%)
    0 / 30 (0.00%)
         occurrences all number
    1
    0
    Urethral Irritation
         subjects affected / exposed
    1 / 30 (3.33%)
    0 / 30 (0.00%)
         occurrences all number
    1
    0
    Musculoskeletal and connective tissue disorders
    Achilles Tendonitis
         subjects affected / exposed
    1 / 30 (3.33%)
    0 / 30 (0.00%)
         occurrences all number
    1
    0
    Back Pain
         subjects affected / exposed
    1 / 30 (3.33%)
    1 / 30 (3.33%)
         occurrences all number
    1
    1
    Low Back Pain
         subjects affected / exposed
    1 / 30 (3.33%)
    0 / 30 (0.00%)
         occurrences all number
    1
    0
    Muscle Swelling
         subjects affected / exposed
    0 / 30 (0.00%)
    1 / 30 (3.33%)
         occurrences all number
    0
    1
    Musculoskeletal Pain
         subjects affected / exposed
    1 / 30 (3.33%)
    0 / 30 (0.00%)
         occurrences all number
    1
    0
    Pain In Arm
         subjects affected / exposed
    0 / 30 (0.00%)
    1 / 30 (3.33%)
         occurrences all number
    0
    1
    Infections and infestations
    Acute Hepatitis A
         subjects affected / exposed
    1 / 30 (3.33%)
    1 / 30 (3.33%)
         occurrences all number
    1
    1
    Acute Upper Respiratory Tract Infection
         subjects affected / exposed
    1 / 30 (3.33%)
    0 / 30 (0.00%)
         occurrences all number
    1
    0
    Cold
         subjects affected / exposed
    1 / 30 (3.33%)
    3 / 30 (10.00%)
         occurrences all number
    1
    3
    Cold Sore
         subjects affected / exposed
    1 / 30 (3.33%)
    0 / 30 (0.00%)
         occurrences all number
    1
    0
    Common Cold
         subjects affected / exposed
    0 / 30 (0.00%)
    1 / 30 (3.33%)
         occurrences all number
    0
    1
    Coryzal Illness
         subjects affected / exposed
    1 / 30 (3.33%)
    0 / 30 (0.00%)
         occurrences all number
    1
    0
    Coryzal Symptoms
         subjects affected / exposed
    0 / 30 (0.00%)
    2 / 30 (6.67%)
         occurrences all number
    0
    2
    Eye Infection
         subjects affected / exposed
    1 / 30 (3.33%)
    0 / 30 (0.00%)
         occurrences all number
    1
    0
    Flu Symptoms
         subjects affected / exposed
    0 / 30 (0.00%)
    1 / 30 (3.33%)
         occurrences all number
    0
    1
    Folliculitis
         subjects affected / exposed
    1 / 30 (3.33%)
    0 / 30 (0.00%)
         occurrences all number
    1
    0
    Fungal Infection
         subjects affected / exposed
    0 / 30 (0.00%)
    1 / 30 (3.33%)
         occurrences all number
    0
    1
    Furuncle
         subjects affected / exposed
    1 / 30 (3.33%)
    0 / 30 (0.00%)
         occurrences all number
    1
    0
    Gingivitis
         subjects affected / exposed
    0 / 30 (0.00%)
    1 / 30 (3.33%)
         occurrences all number
    0
    1
    Gonorrhoea
         subjects affected / exposed
    2 / 30 (6.67%)
    3 / 30 (10.00%)
         occurrences all number
    2
    3
    Helicobacter Pylori Infection
         subjects affected / exposed
    1 / 30 (3.33%)
    0 / 30 (0.00%)
         occurrences all number
    1
    0
    Influenza
         subjects affected / exposed
    1 / 30 (3.33%)
    0 / 30 (0.00%)
         occurrences all number
    1
    0
    Influenza B Virus Infection
         subjects affected / exposed
    1 / 30 (3.33%)
    0 / 30 (0.00%)
         occurrences all number
    1
    0
    Lymphogranuloma Venereum
         subjects affected / exposed
    0 / 30 (0.00%)
    1 / 30 (3.33%)
         occurrences all number
    0
    1
    Pharyngeal Gonococcal Infection
         subjects affected / exposed
    0 / 30 (0.00%)
    1 / 30 (3.33%)
         occurrences all number
    0
    1
    Proctitis Herpes
         subjects affected / exposed
    1 / 30 (3.33%)
    0 / 30 (0.00%)
         occurrences all number
    1
    0
    Ringworm Of Body
         subjects affected / exposed
    0 / 30 (0.00%)
    1 / 30 (3.33%)
         occurrences all number
    0
    1
    Salmonella Gastroenteritis
         subjects affected / exposed
    0 / 30 (0.00%)
    1 / 30 (3.33%)
         occurrences all number
    0
    1
    Shingles
         subjects affected / exposed
    1 / 30 (3.33%)
    0 / 30 (0.00%)
         occurrences all number
    1
    0
    Syphilis
         subjects affected / exposed
    0 / 30 (0.00%)
    2 / 30 (6.67%)
         occurrences all number
    0
    2
    Tonsillitis
         subjects affected / exposed
    1 / 30 (3.33%)
    0 / 30 (0.00%)
         occurrences all number
    1
    0
    Tooth Abscess
         subjects affected / exposed
    1 / 30 (3.33%)
    0 / 30 (0.00%)
         occurrences all number
    1
    0
    Upper Respiratory Tract Infection
         subjects affected / exposed
    1 / 30 (3.33%)
    2 / 30 (6.67%)
         occurrences all number
    1
    2
    Metabolism and nutrition disorders
    Glucose Tolerance Impaired
         subjects affected / exposed
    0 / 30 (0.00%)
    1 / 30 (3.33%)
         occurrences all number
    0
    1
    Vitamin D Deficiency
         subjects affected / exposed
    0 / 30 (0.00%)
    1 / 30 (3.33%)
         occurrences all number
    0
    1

    More information

    Close Top of page

    Substantial protocol amendments (globally)

    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    03 Jun 2015
    Schedule amended to allow for repeat testing of a participant’s viral load, until this falls below the level of detectability. Trial assessment schedule has been split into two stages, pre and post randomisation, with randomisation becoming a separate visit to ensure all participants have a common baseline. All visits after randomisation are now referred to as post randomisation weeks (PR week), which has been updated throughout. Eligibility assessments including routine blood results and resting 12-lead ECG need to be within 14 days of randomisation. Wording clarified for enrolment exclusion criteria 22. Removed the requirement for participants to attend visits fasted. Changes to the trial assessment schedule only: 1) Screening/baseline visit is now referred to as screening only. 2) Follow up visit at week 08 has been removed. 3) For several visits the volumes and timings of blood samples have been changed. Total blood volume taken across the protocol has increased by 17ml. 4) Visits where quality of life questionnaires are required have changed. Further clarification on the vaccination visits has been included: 1) Specified that the first vaccination (Chad) at PR week 00 must take place within 1 week of randomisation. For participants is Arm A, this visit can be completed over the phone. 2) There is a window of 7 days between the two vaccinations given at PR week 00 and PR08 Day 1. 3) Preliminary results from the BCN01 study are now available. 4) Results from the START study are now available
    03 Jun 2015
    Continued: Event reporting section has been updated : 1) Only grade 3 adverse events are reportable prior to randomisation. Grade 4 events are reportable throughout the study as SAEs. 2) Pregnancy in a partner is now considered a notable event. 3) Vaccine related events have been added to the notable events and are listed in Appendix IV. 4) For SAEs, participants must be identified by study number, 3 letter code and year of birth only. 5) Clarification that HERVs may be investigated as an exploratory outcome. 6) Re-clarification of the end of the interventional phase of the study and end of study.
    23 Jul 2015
    Re-clarification of the investigator’s event reporting responsibilities.
    18 May 2016
    Additional QTc information. Change of QTc and bradycardia eligibility criteria. Trial Assessment Schedule only: Additional ECGs at PR10-1 and PR16 included Eligibility has been updated to: 1) Enable sites to use either Hepatitis C RNA or Hepatitis C antigen test to exclude current infection. 2) Enforce use of the CKD-EPI equation to calculate eGFR. Clarification on use of ART prior to enrolment Removed requirement for participants to return empty/part used Raltegravir Removal co-enrolment in UK Register of HIV seroconverters.
    20 Oct 2016
    Addition of Cohort II – Previously diagnosed participants Additional 18ml blood sample for Merck assay at PR11-1. Change of eGFR eligibility criteria . References to TMG updated to PMG.
    15 Oct 2019
    Change to coordinating centre address and Clinical Project Manager. Addition of annual follow up phase to visit tables. Added lost to follow up definition during long-term follow-up. Change of long-term follow-up requirements. Added clarification on the notification requirements for Notable Events during long-term follow-up.
    14 Jun 2022
    Added VIRIAS substudy information including background, rationale, number of participants, eligibility criteria and visit procedures. Addition of VIRIAS substudy references.

    Interruptions (globally)

    Were there any global interruptions to the trial? No

    Limitations and caveats

    Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data.
    None reported

    Online references

    http://www.ncbi.nlm.nih.gov/pubmed/32085823
    For support, Contact us.
    The status and protocol content of GB trials is no longer updated since 1 January 2021. For the UK, as of 31 January 2021, EU Law applies only to the territory of Northern Ireland (NI) to the extent foreseen in the Protocol on Ireland/NI. Legal notice
    As of 31 January 2023, all EU/EEA initial clinical trial applications must be submitted through CTIS . Updated EudraCT trials information and information on PIP/Art 46 trials conducted exclusively in third countries continues to be submitted through EudraCT and published on this website.

    European Medicines Agency © 1995-Fri May 03 17:56:19 CEST 2024 | Domenico Scarlattilaan 6, 1083 HS Amsterdam, The Netherlands
    EMA HMA