Tnf Inhibitors to Reduce Mortality in HIV-1 Infected PAtients With Tuberculosis meNIngitis

• Status: Not yet recruiting
• Trial end date: 2025-03-01
• Target enrollment: 0
• Participant gender: All

Summary

Randomized phase II clinical trial which aims to assess the impact on 3-month mortality and safety of adding adalimumab to standard treatment (anti-tuberculosis drugs and corticosteroids) in HIV patients with tuberculosis meningitis in 3 countries (Brazil, Mozambique, and Zambia).

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: ANRS, Emerging Infectious Diseases
• Treatments: Adalimumab

Criteria

Inclusion Criteria:

• Age ≥18 years

• HIV-1 infection

• ART-naïve or ART discontinued for at least 6 months

• Definite or probable tuberculosis meningitis

• Standard tuberculosis meningitis treatment ≤3 days: anti TB drugs at standard doses and high-dose dexamethasone as per WHO guidelines

• Signed informed consent form by patient or relative.

Exclusion Criteria:

• Other concomitant neurological infection, i.e. toxoplasmosis, cryptococcosis, progressive multifocal leukoencephalopathy, bacterial meningitis, neuro-syphilis

• Asymptomatic positive cryptococcal antigen in serum

• HIV-2 infection (single or dual)

• HBsAg positive or anti hepatitis C virus antibodies positive

• Alanine transaminase (ALT)>5 ULN

• Rifampicin-resistant TB detected by GeneXpert MTB/RIF Ultra

• History of previous TB treatment in patients with GeneXpert MTB/RIF Ultra negative or unavailable

• Current use of drugs contraindicated with study drugs and that cannot be safely stopped

• Allergy to study drugs or any of their components

• Uncontrolled opportunistic infection

• Moderate to severe cardiac insufficiency (NYHA classes III / IV)

• Any condition which might, in the investigator's opinion, compromise the safety of treatment and/or patient's adherence to study procedures

• For women of childbearing age: 1) Pregnancy or breastfeeding; 2) Refusal to use effective contraception to be discussed with the investigator

• Subjects participating in another clinical trial evaluating therapies and including an exclusion period that is still in force during the screening phase

• Person under guardianship, or deprived of freedom by a judicial or administrative decision

• Positive SARS COV-2 test (according to hospital procedures at the time of inclusion)