Toll-like Receptor 9 Agonist Treatment in Chronic HIV-1 Infection

University of Aarhus12 enrolled

Overview

Combination antiretroviral treatment (cART) effectively suppresses virus replication and partially restores immune functions. However, cART cannot cure HIV infection. This study aim to investigate whether the antiviral immune response can be enhanced and/or viral transcription reactivated with MGN1703. MGN1703 is an agonist to toll-like receptor (TLR) 9. Activation of TLR9 has been shown to augment innate and adaptive immune effector functions, most notably enhanced NK cell and T cell functions. Furthermore, TLR9 agonists have been shown in vitro to reactivate viral transcription in latently infected cells, potentially leading to enhanced recognition of infected cells by the immune effector cells.

In Part A, participants will receive 4 weeks MGN1703 therapy (60 mg s.c. twice weekly). During the 4 weeks, participants will be closely monitored for safety and therapeutic effects of the drug. Targeted enrolment in Part A is 14-16 study subjects. In Part B, participants will receive 24 weeks of MGN1703 therapy (60 mg s.c. twice weekly). During the 24 weeks, participants will be frequently monitored for safety and therapeutic effects of the drug. Targeted enrolment in Part B is 10-12 study subjects, preferentially recruited from part A.

Study Type

INTERVENTIONAL

Allocation

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

HIV

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

Inclusion Criteria: * Documented HIV-1 infection * Age \>18 years * CD4+ T-cell count \>350/µL at screening * On cART (for a minimum of 12 months) * Able to give informed consent. Exclusion Criteria: * Pregnancy as determined by a positive urine beta-hCG (if female) * Males or females who are unwilling or unable to use barrier contraception during sexual intercourse for the entire study period. * Currently breast-feeding (if female) * Viral load (HIV RNA) \> 50 copies/mL * Contraindication to receive MGN1703 as per current investigator brochure * Presence of acute bacterial infection or undiagnosed febrile condition * Concurrent chronic systemic immune therapy or immunosuppressant medication, including continuous systemic steroid treatment within the last 2 weeks prior to randomization * Use of antibiotic therapy within the last 2 weeks prior to randomization * Known HBV or HCV infection * Any medical, psychiatric, social, or occupational condition or other responsibility that, in the judgment of the Principal Investigator (PI), would interfere with the evaluation of study objectives (such as severe alcohol abuse, severe drug abuse, dementia) * Unable to follow protocol regimen

Outcomes

Primary Outcomes

Part A: NK cell activation

As measured by CD69 expression

Time frame: 12 weeks

Part B: Quantification of the size of the HIV reservoir

As measured by quantitative viral outgrowth (qVOA) and total HIV DNA

Time frame: 32 weeks

Secondary Outcomes

Safety and tolerability, as measured by adverse events (AE), adverse reactions (AR), serious adverse events (SAE), serious adverse reactions (SAR) and suspected unexpected serious adverse reactions (SUSAR).

Safety evaluation, as measured by adverse events (AE), adverse reactions (AR), serious adverse events (SAE), serious adverse reactions (SAR) and suspected unexpected serious adverse reactions (SUSAR).

Time frame: 12 weeks

The size of the HIV-1 reservoir

HIV DNA and others measures

Time frame: 12 weeks

Viral transcription

Plasma HIV RNA and cell-associated unspliced HIV RNA

Time frame: 12 weeks

Toll-like Receptor 9 Agonist Treatment in Chronic HIV-1 Infection

Overview

Conditions

Interventions

Eligibility

Locations (2)

Outcomes

Primary Outcomes

Secondary Outcomes