Trial Outcomes & Findings for Research In Viral Eradication of HIV Reservoirs (NCT NCT02336074)
NCT ID: NCT02336074
Last Updated: 2023-10-23
Results Overview
The average of two measures taken at post-randomisation week 16 and 18
Recruitment status
COMPLETED
Study phase
PHASE2
Target enrollment
60 participants
Primary outcome timeframe
Averaged across post-randomisation week 16 and 18
Results posted on
2023-10-23
Participant Flow
Participants were recruited from 6 UK clinical sites. The recruitment period was from November 2015 until July 2017. Last patient last visit was completed in November 2017.
Participants were recruited from two Strata: 1. Recently diagnosed with primary HIV-1 infection - Eligible participants were enrolled at week 0 when combination ART (cART) began. Randomisation occurred at week 22 2. Previously diagnosed with primary HIV-1 infection - Randomisation occurred within 2 weeks of screening.
Participant milestones
| Measure |
Control
Participants received combination Antiretroviral Therapy (cART) preferably including raltegravir prescribed for the duration of the study
|
Intervention
Participants received combination Antiretroviral Therapy (cART) preferably including raltegravir prescribed for the duration of the study 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).
|
|---|---|---|
|
Overall Study
STARTED
|
30
|
30
|
|
Overall Study
COMPLETED
|
30
|
28
|
|
Overall Study
NOT COMPLETED
|
0
|
2
|
Reasons for withdrawal
| Measure |
Control
Participants received combination Antiretroviral Therapy (cART) preferably including raltegravir prescribed for the duration of the study
|
Intervention
Participants received combination Antiretroviral Therapy (cART) preferably including raltegravir prescribed for the duration of the study 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).
|
|---|---|---|
|
Overall Study
Adverse Event
|
0
|
2
|
Baseline Characteristics
Research In Viral Eradication of HIV Reservoirs
Baseline characteristics by cohort
| Measure |
Control (Arm A - ART Only)
n=30 Participants
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)
|
Intervention (Arm B - ART + Vaccines + Vorinostat)
n=30 Participants
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).
|
Total
n=60 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Categorical
<=18 years
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
30 Participants
n=5 Participants
|
30 Participants
n=7 Participants
|
60 Participants
n=5 Participants
|
|
Age, Categorical
>=65 years
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Age, Continuous
|
31 years
n=5 Participants
|
35 years
n=7 Participants
|
32 years
n=5 Participants
|
|
Sex: Female, Male
Female
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
30 Participants
n=5 Participants
|
30 Participants
n=7 Participants
|
60 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
White
|
16 Participants
n=5 Participants
|
26 Participants
n=7 Participants
|
42 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
South Asian
|
0 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
South East Asian
|
1 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Hispanic/Latino
|
3 Participants
n=5 Participants
|
2 Participants
n=7 Participants
|
5 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Black Caribbean/American
|
2 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
2 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Black African
|
2 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
2 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Mixed ethnic group
|
5 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
6 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Other
|
1 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
|
Mode of HIV Infection
MSM
|
26 Participants
n=5 Participants
|
29 Participants
n=7 Participants
|
55 Participants
n=5 Participants
|
|
Mode of HIV Infection
MSW
|
1 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
2 Participants
n=5 Participants
|
|
Mode of HIV Infection
MSM + IDU
|
2 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
2 Participants
n=5 Participants
|
|
Mode of HIV Infection
Unknown
|
1 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
|
CD4 at randomisation
|
694 cells/mm3
n=5 Participants
|
710 cells/mm3
n=7 Participants
|
708 cells/mm3
n=5 Participants
|
|
HIV RNA at randomisation (copies/ml)
<50
|
29 Participants
n=5 Participants
|
30 Participants
n=7 Participants
|
59 Participants
n=5 Participants
|
|
HIV RNA at randomisation (copies/ml)
50 - <200
|
1 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
|
Weeks since PHI diagnosis
<= 1 week
|
1 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
|
Weeks since PHI diagnosis
>1 - 2 weeks
|
3 Participants
n=5 Participants
|
3 Participants
n=7 Participants
|
6 Participants
n=5 Participants
|
|
Weeks since PHI diagnosis
>2 - 3 weeks
|
7 Participants
n=5 Participants
|
7 Participants
n=7 Participants
|
14 Participants
n=5 Participants
|
|
Weeks since PHI diagnosis
>3 - 4 weeks
|
15 Participants
n=5 Participants
|
16 Participants
n=7 Participants
|
31 Participants
n=5 Participants
|
|
Weeks since PHI diagnosis
> 4 weeks
|
4 Participants
n=5 Participants
|
4 Participants
n=7 Participants
|
8 Participants
n=5 Participants
|
|
Weeks since PHI diagnosis (at randomisation)
|
28 weeks
n=5 Participants
|
28 weeks
n=7 Participants
|
28 weeks
n=5 Participants
|
PRIMARY outcome
Timeframe: Averaged across post-randomisation week 16 and 18The average of two measures taken at post-randomisation week 16 and 18
Outcome measures
| Measure |
Control (Arm A - ART Only)
n=30 Participants
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)
|
Intervention (Arm B - ART + Vaccines + Vorinostat)
n=30 Participants
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).
|
|---|---|---|
|
Total HIV DNA From CD4 T-cells
|
2.95 HIV-DNA copies/mill CD4+ T cells (log10)
Standard Deviation 0.50
|
3.06 HIV-DNA copies/mill CD4+ T cells (log10)
Standard Deviation 0.49
|
SECONDARY outcome
Timeframe: From randomization to the final visit at week 18.Population: All participants randomized
Clinical adverse events of any grade post-randomization.
Outcome measures
| Measure |
Control (Arm A - ART Only)
n=30 Participants
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)
|
Intervention (Arm B - ART + Vaccines + Vorinostat)
n=30 Participants
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).
|
|---|---|---|
|
Clinical Adverse Events
Not had any event
|
8 Participants
|
1 Participants
|
|
Clinical Adverse Events
Did have any event
|
22 Participants
|
29 Participants
|
SECONDARY outcome
Timeframe: At week 16Population: All participants randomized with valid assay results at week 16.
Number of Participants with undetectable quantitative viral outgrowth
Outcome measures
| Measure |
Control (Arm A - ART Only)
n=29 Participants
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)
|
Intervention (Arm B - ART + Vaccines + Vorinostat)
n=27 Participants
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).
|
|---|---|---|
|
Quantitative Viral Outgrowth
|
12 Participants with undetectable outgrowth
|
6 Participants with undetectable outgrowth
|
SECONDARY outcome
Timeframe: 12 weeksPopulation: All participants randomized with valid assay results
Percentage of CD4+ CD154+ IFNγ+ T cells , assessed using an optimized and qualified flow cytometry panel.
Outcome measures
| Measure |
Control (Arm A - ART Only)
n=27 Participants
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)
|
Intervention (Arm B - ART + Vaccines + Vorinostat)
n=30 Participants
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).
|
|---|---|---|
|
Percentage of CD4+ CD154+ IFNγ+ T Cells
Post randomisation week 9
|
0.006 % cells CD4+ CD154+ IFNγ+
Interval 0.0 to 0.015
|
0.097 % cells CD4+ CD154+ IFNγ+
Interval 0.043 to 0.161
|
|
Percentage of CD4+ CD154+ IFNγ+ T Cells
Post randomisation week 12
|
0.006 % cells CD4+ CD154+ IFNγ+
Interval 0.0 to 0.015
|
0.109 % cells CD4+ CD154+ IFNγ+
Interval 0.05 to 0.214
|
SECONDARY outcome
Timeframe: 12 weeksPercentage of CD8+ CD107a+ IFNγ+ T cells , assessed using an optimized and qualified flow cytometry panel.
Outcome measures
| Measure |
Control (Arm A - ART Only)
n=27 Participants
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)
|
Intervention (Arm B - ART + Vaccines + Vorinostat)
n=30 Participants
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).
|
|---|---|---|
|
CD8+ T-cell Responses
Post randomisation week 12
|
0.062 % cells CD8+ CD107a+ IFNγ+
Interval 0.008 to 0.106
|
0.263 % cells CD8+ CD107a+ IFNγ+
Interval 0.105 to 0.62
|
|
CD8+ T-cell Responses
Post randomisation week 9
|
0.052 % cells CD8+ CD107a+ IFNγ+
Interval 0.014 to 0.142
|
0.194 % cells CD8+ CD107a+ IFNγ+
Interval 0.142 to 0.722
|
SECONDARY outcome
Timeframe: 12 weeksPopulation: All participants randomized with valid assay results
CD8+ T cell antiviral suppressive activity was expressed as percentage elimination 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. Viral inhibition Assay
Outcome measures
| Measure |
Control (Arm A - ART Only)
n=27 Participants
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)
|
Intervention (Arm B - ART + Vaccines + Vorinostat)
n=30 Participants
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).
|
|---|---|---|
|
Viral Inhibition
|
-18.25 Percentage elimination
Interval -29.65 to -6.85
|
1.50 Percentage elimination
Interval -11.28 to 14.27
|
POST_HOC outcome
Timeframe: 12 weeksPopulation: Intervention arm only - histone H4 acetylation was only measured in participants in the intervention arm with the aim to compare values approximately 2 hours post vorinostat intake with values pre vorinostat intake. No data were collected from participants in the control arm.
Histone H4 acetylation using a H4K5/8/12/16 immunoassay with thawed PBMC derived cell lysates added to an ELISA using anti-H4 monoclonal antibody
Outcome measures
| Measure |
Control (Arm A - ART Only)
n=22 Participants
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)
|
Intervention (Arm B - ART + Vaccines + Vorinostat)
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).
|
|---|---|---|
|
Histone H4 Acetylation
|
3.19 Fold increase pre to post vorinostat
Interval 2.42 to 4.22
|
—
|
Adverse Events
Control
Serious events: 0 serious events
Other events: 6 other events
Deaths: 0 deaths
Intervention
Serious events: 1 serious events
Other events: 1 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Control
n=30 participants at risk
ART only
Combination ART (cART) preferably including raltegravir (control)
|
Intervention
n=30 participants at risk
ART plus vaccines plus vorinostat
Combination ART (cART) preferably including raltegravir\* plus ChAdV63.HIVconsv (ChAd) prime and MVA.HIVconsv (MVA) boost vaccines; followed by a 28-day course of vorinostat (10 doses in total).
|
|---|---|---|
|
Vascular disorders
Vasovagal syncope
|
0.00%
0/30 • 18 weeks
|
3.3%
1/30 • Number of events 1 • 18 weeks
|
Other adverse events
| Measure |
Control
n=30 participants at risk
ART only
Combination ART (cART) preferably including raltegravir (control)
|
Intervention
n=30 participants at risk
ART plus vaccines plus vorinostat
Combination ART (cART) preferably including raltegravir\* plus ChAdV63.HIVconsv (ChAd) prime and MVA.HIVconsv (MVA) boost vaccines; followed by a 28-day course of vorinostat (10 doses in total).
|
|---|---|---|
|
Hepatobiliary disorders
Acute hepatitis A
|
3.3%
1/30 • Number of events 1 • 18 weeks
|
0.00%
0/30 • 18 weeks
|
|
Infections and infestations
Influenza
|
3.3%
1/30 • Number of events 1 • 18 weeks
|
0.00%
0/30 • 18 weeks
|
|
Skin and subcutaneous tissue disorders
Proctitis herpes
|
3.3%
1/30 • Number of events 1 • 18 weeks
|
0.00%
0/30 • 18 weeks
|
|
Infections and infestations
Shingles
|
3.3%
1/30 • Number of events 1 • 18 weeks
|
0.00%
0/30 • 18 weeks
|
|
Injury, poisoning and procedural complications
Wrist injury
|
3.3%
1/30 • Number of events 1 • 18 weeks
|
0.00%
0/30 • 18 weeks
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
3.3%
1/30 • Number of events 1 • 18 weeks
|
3.3%
1/30 • Number of events 1 • 18 weeks
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee The NHS Organisations shall not publish or otherwise disseminate conclusions of the Study, including all or any part of the Results of the Study without prior written consent of the Sponsor, such consent not to be unreasonably withheld or delayed.
- Publication restrictions are in place
Restriction type: OTHER