Phase 2
N=60
Research In Viral Eradication of HIV Reservoirs
HIV
Bottom Line
View on ClinicalTrials.gov: NCT02336074 ↗Enrolled (actual)
60
Serious AEs
1.7%
Results posted
Sep 2019
Primary outcome: Primary: Total HIV DNA From CD4 T-cells — 2.95; 3.06 HIV-DNA copies/mill CD4+ T cells (log10) — p=0.26
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 2
- Interventions
- Combination Antiretroviral Therapy (cART) (Drug); Raltegravir (Drug); Vorinostat (Drug); ChAdV63.HIVconsv (ChAd) (Biological); MVA.HIVconsv (MVA) (Biological)
- Age
- Adult · 18+ yrs
- Sex
- All
- Sponsor
- Imperial College London
- Primary completion
- Nov 2017
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Total HIV DNA From CD4 T-cells |
2.95; 3.06 | 0.26 |
| SECONDARY Clinical Adverse Events |
8; 1; 22; 29 | — |
| SECONDARY Quantitative Viral Outgrowth |
12; 6 | 0.145 |
| SECONDARY Percentage of CD4+ CD154+ IFNγ+ T Cells |
0.006; 0.097; 0.006; 0.109 | — |
| SECONDARY CD8+ T-cell Responses |
0.052; 0.194; 0.062; 0.263 | — |
| SECONDARY Viral Inhibition |
-18.25; 1.50 | — |
Summary
This study will be a two-arm prospective 1:1 randomised controlled trial comparing:
Arm A: cART preferably including raltegravir (combination ART cART - control) Arm B: cART preferably including raltegravir (cART) plus ChAdV63.HIVconsv (ChAd) prime and MVA.HIVconsv (MVA) boost vaccines; followed by a 28-day course of vorinostat (10 doses in total).
We hypothesise that this intervention in primary HIV infection will confer a significant reduction in the latent HIV reservoir when compared with cART alone.
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Eligibility Criteria
Inclusion criteria
- Aged ≥18 to ≤60 years old
- Able to give informed written consent including consent to long-term follow-up
- Should be enrolled within a maximum of 4 weeks of a diagnosis of primary HIV-1 infection confirmed by one of the following criteria:
- Positive HIV-1 serology within a maximum of 12 weeks of a documented negative HIV-1 serology test result (can include point of care test (POCT) using blood for both tests)
- A positive p24 antigen result and a negative HIV antibody test
- Negative antibody test with either detectable HIV RNA or proviral DNA
- PHE RITA test algorithm (a) reported as "Incident" confirming the HIV-1 antibody avidity is consistent with recent infection (within the preceding 16 weeks).
- Weakly reactive or equivocal 4th generation HIV antibody antigen test
- Equivocal or reactive antibody test with 7%
- Any congenital or acquired prolongation of the QTc interval, with normal defined as ≤0.44s (≤440ms)
- Participation in any other clinical trial of an experimental agent or any non-interventional study where additional blood draws are required; participation in an observational study is permitted
- Allergy to egg
- History of anaphylaxis or severe adverse reaction to vaccines
- Planned receipt of vaccines within 2 weeks of the first trial vaccination administered at PR week 00 (including vaccines such as yellow fever; hepatitis B, influenza)
- Abnormal blood test results at screening including:
- Moderate to severe hepatic impairment as defined by Child-Pugh classification
- ALT >5xULN
- Platelets 30 mg/mmol
- Physical and laboratory test findings: Evidence of organ dysfunction or any clinically significant deviation from normal in physical examination and/or vital signs that the investigator believes is a preclusion from enrolment into the study
- Active alcohol or substance use that, in the Investigator's opinion, will prevent adequate adherence with study requirements
- Insufficient venous access that will allow scheduled blood draws as per protocol
- using current cut-offs for optical density as defined by PHE
- females aged 3500mL before to participate. This circumstance is unlikely to arise as most women between the ages of 18 to 20 years would be of child-bearing potential (CBP) and excluded on that basis.
- eGFR is calculated by the local labs using CKD-EPI. Units ml/min/1.73m2.
Data sourced from ClinicalTrials.gov (NCT02336074). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.