NCT07028385

Safety and Impact of Baricitinib on Cell Surivival Pathways, HIV-1 Reservoir and Inflamation in People With HIV-1

Exploratory Phase 2 Randomized, Double-blind, Placebo-Controlled Study to Evaluate the Safety and Impact on HIV-1 Reservoir of Baricitinib in Virologically Suppressed People With HIV-1

• Status: Active Not Recruiting
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 30 (estimated)
• Sponsor: Fundación FLS de Lucha Contra el Sida, las Enfermedades Infecciosas y la Promoción de la Salud y la Ciencia · Academic / Other
• Sex: All
• Age: 18 Years – 64 Years
• Healthy volunteers: Not accepted

Summary

The goal of this exploratory clinical trial is to evaluate the safety and tolerability of bariticinib administered at 2 mg once daily during 12 weeks in 30 people living with HIV-1 (PWH) on suppressive antiretroviral therapy (ART) and to evaluate changes in levels of phosphorylated STAT (pSTAT) after 12 weeks of treatment with bariticinib. The main questions it aims to answer are: * The safety and tolerability of bariticinib * To evaluate the effects of bariticinib on T-cells (HIV-1 reservoirs, apoptosis, inflamation, activation and exhaustion). * To characterize bariticinib pharmacokinetics in plasma. Participants will be treated with pral Barticinib 2mg or matched Placebo daily for 12 weeks. Suppressive cART will remain unchanged during the entire study. Participants will be followed until week 24, in a total of 8 visits.

Detailed description

Despite the success of antiretroviral therapy (ART) in suppressing HIV replication, it does not eliminate the latent viral reservoir, which remains a major barrier to achieving a cure. Recent evidence suggests that HIV-infected cells may evade immune clearance by overexpressing anti-apoptotic proteins such as BCL-2, contributing to reservoir persistence. Baricitinib, a second-generation Janus kinase (JAK) inhibitor has shown potential in preclinical studies to reduce HIV reactivation and modulate immune activation. This study investigates whether baricitinib can safely modulate the HIV-1 reservoir and immune environment in PWH on suppressive ART. Participants will be randomized (2:1) to receive either oral baricitinib 2 mg or placebo daily for 12 weeks, followed by a 12-week observation period. The primary objectives are to assess the safety and tolerability of baricitinib and to evaluate changes in phosphorylated STAT (pSTAT) levels in CD4+ T cells as a pharmacodynamic marker. Secondary objectives include evaluating the effects of baricitinib on BCL-2 expression, JAK/STAT signaling, HIV-1 reservoir size, inflammatory biomarkers, and immune cell subsets. Exploratory analyses will assess HIV-specific T cell responses, CD4+ T cell susceptibility to cytotoxic T lymphocyte (CTL) killing, and transcriptomic changes.

Conditions

• HIV

Interventions

Type	Name	Description
DRUG	Bariticinib 2 mg	Commercially available tablets containing 2 mg of barticiinib will be used. The tablets will be re-capsulated to keep the study blind.
OTHER	Placebo	Maltodextrin capsules with identical weight and appearance (shape, size, colour and flavour) as the bariticinib-containing capsules.

Timeline

• Start date: 2025-09-22
• Primary completion: 2026-04-01
• Completion: 2026-07-01
• First posted: 2025-06-19
• Last updated: 2026-02-27

Locations

1 site across 1 country: Spain