Research In Viral Eradication of HIV Reservoirs

Launched by IMPERIAL COLLEGE LONDON · Jan 7, 2015

Keywords

ClinConnect Summary

The study design is a two-arm, open label randomised study. Eligible participants are recruited from two participant cohorts (Cohort I - Recently diagnosed or Cohort II - Previously diagnosed with HIV). All participants receive combination ART (cART) for the duration of the intervention phase of the study (Cohort I: 42 weeks, Cohort II: 18 weeks). In patients meeting the criteria for randomisation (eligibility assessed at week 22/screening), participants will either continue cART or receive an intervention consisting of two anti-HIV vaccines separated by 8 weeks followed by 10 doses of the ...

Gender

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Eligibility criteria

• • Inclusion criteria
• • 1. Aged ≥18 to ≤60 years old
• • 2. Able to give informed written consent including consent to long-term follow-up
• 3. Should be enrolled within a maximum of 4 weeks of a diagnosis of primary HIV-1 infection confirmed by one of the following criteria:
• • 1. 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)
• • 2. A positive p24 antigen result and a negative HIV antibody test
• • 3. Negative antibody test with either detectable HIV RNA or proviral DNA
• • 4. PHE RITA test algorithm (a) reported as "Incident" confirming the HIV-1 antibody avidity is consistent with recent infection (within the preceding 16 weeks).
• • 5. Weakly reactive or equivocal 4th generation HIV antibody antigen test
• • 6. Equivocal or reactive antibody test with \<4 bands on western blot
• • 4. Adequate haemoglobin (Hb≥12g/dL for males, ≥11g/dL for females)
• • 5. Weight ≥50kg
• • 6. Willing to be treated with cART (preferably including raltegravir) and be randomised to continue cART alone or cART plus intervention (HIV vaccines plus HDACi)
• • 7. Willing and able to comply with visit schedule and provide blood sampling
• • Exclusion criteria
• • 1. Women of child bearing potential (WCBP) (b)
• • 2. In women with intact ovaries and no uterus, any planned egg donation anytime in the future to a surrogate
• • 3. Intention to donate sperm or father a child within 6 months of the intervention
• • 4. Co-infection with hepatitis B (surface antigen positive or detectable HBV DNA levels in blood) or hepatitis C (HCV RNA positive or HVC antigen positive)
• • 5. Any current or past history of malignancy
• • 6. Concurrent opportunistic infection or other comorbidity or comorbidity likely to occur during the trial e.g.past history of ischaemic or other significant heart disease, malabsorption syndromes, autoimmune disease
• • 7. Any contraindication to receipt of BHIVA recommended combination antiretrovirals
• • 8. HIV-2 infection
• • 9. Known HTLV-1 co-infection
• • 10. Prior immunisation with any experimental HIV Immunogens (including any component of the vaccines used in the RIVER protocol; simian or human adenoviral vaccine; other experimental HIV vaccines)
• • 11. Current or planned systemic immunosuppressive therapy (inhaled corticosteroids are allowed)
• • 12. Any history of proven thromboembolism (pulmonary embolism or deep vein thrombosis)
• • 13. Any inherited or acquired bleeding diathesis including gastric or duodenal ulcers, varices
• • 14. Concurrent or planned use of any drugs contraindicated with vorinostat i.e. antiarrhythmics; any other drugs that prolong QTc; warfarin, aspirin, sodium valproate
• • 15. Prior intolerance of any of either the components of the vaccine or HDACi,
• • 16. Uncontrolled diabetes mellitus defined as an HBA1C\>7%
• • 17. Any congenital or acquired prolongation of the QTc interval, with normal defined as ≤0.44s (≤440ms)
• • 18. 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
• • 19. Allergy to egg
• • 20. History of anaphylaxis or severe adverse reaction to vaccines
• • 21. 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)
• 22. Abnormal blood test results at screening including:
• • 1. Moderate to severe hepatic impairment as defined by Child-Pugh classification
• • 2. ALT \>5xULN
• • 3. Platelets \<150x109/L
• • 4. eGFR \<60 (c)
• • 5. uPCR \>30 mg/mmol
• • 23. 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
• • 24. Active alcohol or substance use that, in the Investigator's opinion, will prevent adequate adherence with study requirements
• • 25. Insufficient venous access that will allow scheduled blood draws as per protocol
• • 1. using current cut-offs for optical density as defined by PHE
• • 2. females aged \<20 years of age, and weighing \<65kg and \<168cm in height will need to have an estimation of blood volume (EBV) prior to enrolment, \>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.
• • 3. eGFR is calculated by the local labs using CKD-EPI. Units ml/min/1.73m2.