Study of Combined GARP:TGF-β1/PD-1 Blockade as a Shock-and-kill Strategy in HIV-1 Cure

NCT07692932 | Not Yet Recruiting

• 1 other identifier: 2026/03FEV/065
• Study Type: interventional
• Target: 100
• Locations: 1 country
• Sites: 1

Brief Summary

The persistence of a reservoir of long-lived, latently infected cells carrying replication-competent proviral DNA constitutes the main barrier to Human Immunodeficiency Virus type 1 (HIV-1) cure. Recent research on HIV cure has focused strategies to "purge" the viral reservoir either to eradicate the infection or, at least, delay the time to viral recrudescence after antiretroviral treatment (ART) interruption. On the other hand, chronic HIV-1 infection is characterized by a dysfunctional state of CD8+ T cells. A long-standing approach has been the establishment of latency reversal (LR) strategies, aiming to pharmacologically reactivate viral expression in latently infected cells, exposing them to clearance by CD8+ T cells or death through viral cytolysis. Strategies have also been developed to stimulate virus-specific CD8+ T cells. This global approach is called "shock-and-kill". PD-1 blockade has been shown to be able to both facilitate LR and reverse CD8+ T cell dysfunction in HIV-1 ex vivo. Clinical studies evaluating PD-(L)1 blockade in people living with HIV (PLWHIV) without cancer provide promising evidence for both immunologic and virologic response but also highlight the main limitations of immune checkpoint blockade (ICB) in PLWHIV: variable and transient responses to the treatment, and a safety concern. Combination with other ICB would be a relevant approach. Anti-GARP:TGF-β1 monoclonal antibodies overcome resistance to anti-PD-1 immunotherapy in murine models of cancer, resulting from the increase in numbers or effector functions of anti-tumor CD8+ T cells. These findings have been subsequently translated into clinical research, with a phase I first-in-human study in patients with solid tumors. In HIV-1 infection, TGF-β1 is involved in disease progression and pathogenesis, notably in the establishment of the reservoir. The inhibition of TGF-β1 receptor by its inhibitor (galunisertib) has been shown to increase LR in HIV ex-vivo as well as in a in-vivo model with SIV. In the simian model, galunisertib also enhanced anti-SIV immune response and decreased SIV reservoir size. This study will assess, in an ex vivo model, whether the addition of GARP:TGF-β1 blockade to PD-1 blockade enhances the virologic and/or immunologic responses, in a shock-and-kill combined strategy.

Conditions

HIV -1 Infection

Keywords

HIV; HIV-1; Immune checkpoint blockade; PD-1; TGF-β1

Outcome Measures

Primary Outcomes (1)

• HIV-1 reservoir shrinkage

  To assess the additive and/or synergistic effect of GARP:TGF-β1 blockade when added to PD-1 blockade in terms of LR and enhancement of HIV-specific T cellular response in HIV-1, in order to evaluate the benefit of a combined immunotherapy as a "shock-and-kill" treatment aiming towards HIV cure.

  on blood draw on day 1

Secondary Outcomes (2)

• reversal of immune exhaustion

  on blood drawn on day 1

• Latency reversal

  on blood drawn on day 1

Study Arms (1)

blood drawn

EXPERIMENTAL

blood drawn

Other: blood drawn

Interventions

blood drawn OTHER

blood drawn

blood drawn

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Adults (min 18 years old).
• HIV-1 subtype B infected and regularly followed at Centre de reference HIV of Cliniques Universitaires Saint-Luc.
• Treated on cART and virologically suppressed.

You may not qualify if:

• Elite controlers
• Chronic hepatitis B or C co-infection.
• Vulnerable subjects.

Sponsors & Collaborators

• Cliniques universitaires Saint-Luc- Université Catholique de Louvain: lead

Study Sites (1)

Cliniques Universitaires Saint-Luc

Brussels, Brussels Capital, 1200, Belgium

Location

Study Officials

• Sophie Lucas, MD, PhD

  Université Catholique de Louvain

  STUDY CHAIR

• Jean Cyr Yombi, MD

  Cliniques universitaires Saint-Luc- Université Catholique de Louvain

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Laurence Bamps, MD

CONTACT

+3227648286; laurence.bamps@saintluc.uclouvain.be

Céline D'Aoust

CONTACT

+3227642190; infectiology-research@saintluc.uclouvain.be

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 3, 2026
• First Posted: July 9, 2026
• Study Start (Estimated): August 31, 2026
• Primary Completion (Estimated): December 31, 2030
• Study Completion (Estimated): December 31, 2030
• Last Updated: July 9, 2026

Record last verified: 2026-06

Locations

BE (1)