RIVER - Research in Viral Eradication of HIV Reservoirs

Recruitment & Eligibility

Status: Authorised-recruitment may be ongoing or finished

Sex: All

Target Recruitment: 60

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:
a.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))
b.A positive p24 antigen result and a negative HIV antibody test
c.Negative antibody test with either detectable HIV RNA or proviral DNA
d.PHE RITA test algorithm (a) reported as Incident” confirming the HIV-1 antibody avidity is consistent with recent infection (within the preceding 16 weeks)
e.Weakly reactive or equivocal 4th generation HIV antibody antigen test
f.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 (b)
6.Willing to start immediate cART and be randomised to continue cART alone or cART plus intervention (HIV vaccines plus HDACi) at week 24
7.Willing and able to comply with visit schedule and provide blood sampling

(a)using current cut-offs for optical density as defined by PHE
(b)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.

Are the trial subjects under 18? no
Number of subjects for this age range: 0
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 60
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range 0

Exclusion Criteria

1.Women of child bearing potential (WCBP) (a)
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)
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.Any contraindication to receipt of the strand-transfer integrase inhibitor (INSTI), raltegravir
9.HIV-2 infection
10.Known HTLV-1 co-infection
11.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)
12.Current or planned systemic immunosuppressive therapy (inhaled corticosteroids are allowed)
13.Any history of proven thromboembolism (pulmonary embolism or deep vein thrombosis)
14.Any inherited or acquired bleeding diathesis including gastric or duodenal ulcers, varices
15.Concurrent or planned use of any drugs contraindicated with vorinostat i.e. antiarrhythmics; any other drugs that prolong QTc; warfarin, aspirin, sodium valproate
16.Prior intolerance of any of either the components of the vaccine or HDACi,
17.Uncontrolled diabetes mellitus defined as an HBA1C>7%
18.Any congenital or acquired prolongation of the QTc interval, with normal defined as ?0.40s (=400ms); bradycardia <55 bpm
19.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
20.Allergy to egg
21.History of anaphylaxis or severe adverse reaction to vaccines
22.Planned receipt of vaccines (including vaccines such as yellow fever; hepatitis B, influenza) within 2 weeks of the first vaccination at week 24 on study
23.Abnormal blood test results at screening including
a.Moderate to severe hepatic impairment as defined by Child-Pugh classification
b.ALT >5xULN
c.Platelets <150x109/L
d.eGFR <90 (b)
e.uPCR >30 mg/mmol
24.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
25.Active alcohol or substance use that, in the Investigator’s opinion, will prevent adequate adherence with study requirements
26.Insufficient venous access that will allow scheduled blood draws as per protocol

(a) defined as any female who has experienced menarche and who has not undergone successful surgical sterilisation (hysterectomy or bilateral oophorectomy) or is not postmenopausal (defined as amenorrhoea = 12 consecutive months; or women on hormone replacement therapy (HRT) with documented serum follicle stimulating hormone (FSH) level > 35mIU/mL); NB bilateral tubal ligation is reversible, a women with only tubal ligation who does not meet any of the other criteria is considered a WCBP.
(b)eGFR is calculated by the local labs using CKD-EPI or MDRD, both equations are acceptable. Units ml/min/1.73m2.