HIV-1-infection
Conditions
Brief summary
This study is designed to evaluate the safety and efficacy of lefitolimod and 3BNC117/10-1074 in HIV-1-infected individuals on ART and during ATI as intervention to reduce the HIV-1 reservoir
Interventions
DRUGSaline
Placebo
DRUGLefitolimod
A TLR9 agonist administered s.c. once weekly for 8 weeks.
Broadly neutralizing antibodies against HIV env administered two times with a 3 week interval.
Sponsors
Aalborg University Hospital
Odense University Hospital
Rigshospitalet, Denmark
Hvidovre University Hospital
The Peter Doherty Institute for Infection and Immunity
University of Utah
Oslo University Hospital
University of Aarhus
Study design
Allocation
RANDOMIZED
Intervention model
FACTORIAL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Masking description
The participant and all study personnel who directly interact with study participants are blinded to study arm designation.
Intervention model description
Participants will be randomized 1:1:1:1 in a blinded fashion to receive: Arm A: Placebo and Placebo Arm B: Lefitolimod and Placebo Arm C: Placebo and 3BNC117+10-1074 Arm D: Lefitolimod and 3BNC117+10-1074
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
* Documented HIV-1 infection * Adults age 18-65 years * On ART for a minimum of 18 months. * CD4+ T cell count \>500 at screening * HIV-1 RNA plasma level of \< 50 copies/mL by standard assays for at least 15 months (a single viral load measurement \> 50 but \< 500 copies/mL during this time period is allowable). * Able to give informed consent * Viral reservoir sensitivity to 3BNC117 and 10-1074. (Sensitivity of the viral reservoir to neutralization by 3BNC117 and 10-1074 will be tested following the screening visit (i.e. prior to randomization)). Sensitivity of the viral reservoir to neutralization by 3BNC117 and 10-1074 will be tested following the screening visit (i.e. prior to enrollment and randomization). Isolated PBMCs will be analyzed using the PhenoSense HIV mAb Assay, Monogram Biosciences. The sensitivity of an individuals archieved proviruses to bNAb neutralization will be determined by the IC50 value of PBMC derived pseudovirus inhibition. Subjects that are considered sensitive to both 3BNC117 (IC90\<=1.5 μg/mL) and 10-1074 (IC90\<=2.0 μg/mL) AND MPI\>97 AND fulfill the other inclusion/
Exclusion criteria
will proceed to study enrolment and randomization. If sensitivity cannot be determined by the PhenoSense HIVmAb Assay, participants will be screened for 3BNC117 and 10-1074 sensitivity using HIV env sequencing carried out in-house (Aarhus, Denmark). The method was originally established and validated by Rockefeller University that already has this method implemented. The method utilizes HIV-1 DNA envelope sequencing and a mathematical prediction binding algoritm of known binding sites of the antibodies. Based on the individual HIV env sequence, proviruses are categorized as sensitive or resistant. Subjects that are determined to be sensitive to both 3BNC117 and 10-1074 (defined as at least 90% of known sequences sensitive to either bNAb) AND fulfill the other inclusion/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Time to re-initiation of cART during analytical treatment interruption (ATI) | Up to 26 weeks. | Time from date of cART cessation to the date of the last of three consecutive plasma HIV-1 RNA measurements \>10,000 copies/mL, CD4 cell count \<350 on two consecutive measurements, or end of ATI (i.e. 26 weeks after cessation of cART) - whichever comes first. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Safety and Tolerability assessment measured by AEs, Adverse Reactions (ARs), SAEs, | Duration of the study | Subject who receives at least one dose of the IMP(s) will be included in the evaluation for safety, measured by AEs, Adverse Reactions (ARs), SAEs, Serious ARs (SARs) and (SUSAR) |
| Plasma HIV RNA doubling time | Duration of ATI (up to 26 weeks) | Plasma HIV RNA doubling time from first measurement \>50 copies/mL to first measurement \>1,000 copies/mL during the analytical treatment interruption (plasma HIV RNA measured by standard clinical assays, e.g. Cobas TaqMan; Lower limit of quantitation 20 copies/mL) |
Countries
Australia, Denmark, Norway, United States
Outcome results
None listed