Prevention of AIDS With Opportunistic Infection Paradoxical IRIS

Overview

This study was a multicenter, open-label, randomized controlled clinical trial designed to evaluate the efficacy and safety of glucocorticoids in preventing paradoxical immune reconstitution inflammatory syndrome (IRIS) in patients with AIDS complicated by opportunistic infections. A total of 262 HIV-infected patients with a baseline CD4⁺ T-cell count \<100/μL, who were scheduled to initiate antiretroviral therapy and had opportunistic infections, were enrolled and randomly assigned in a 1:1 ratio to the prednisolone group or the control group. Participants in the treatment group received prednisolone at 40 mg/day for 14 days followed by 20 mg/day for 14 days, whereas the control group received no glucocorticoid intervention. All participants were followed for 12 weeks. The primary endpoint was the incidence of paradoxical IRIS within 12 weeks. Secondary endpoints included time to IRIS onset, duration of IRIS, mortality, hospitalization, serious adverse events, CD4⁺ T-cell counts, and HIV-RNA suppression. The findings will provide evidence-based support for the prevention of paradoxical IRIS.

Interventions

• Drug Prednisolone
  Prednisolone Group

Primary outcome measures

• Incidence rate of paradoxical IRIS at 12 weeks after enrollment. [Time frame: 12weeks]

Secondary outcome measures (8)

• Time from enrollment to occurrence of paradoxical IRIS [Time frame: within 12weeks]
• Duration of paradoxical IRIS [Time frame: within 12 weeks]
• Death (related to paradoxical IRIS; all-cause mortality) [Time frame: 12weeks]
• Hospitalization (related to paradoxical IRIS; all-cause) [Time frame: 12weeks]
• Composite endpoint of death or hospitalization [Time frame: within 12weeks]
• Incidence rate of serious adverse events [Time frame: 12weeks]
• CD4+ T lymphocyte count at 12 weeks [Time frame: 12weeks]
• Number of patients with HIV-RNA < 20 copies/ml at 12 weeks [Time frame: 12weeks]

Eligibility criteria

Inclusion criteria

• Age ≥ 18 years;
• Confirmed HIV infection;
• Presence of HIV-related opportunistic infection(s), including non-tuberculous -mycobacterial infection, PJP, pneumonia, cryptococcal meningitis, Talaromyces marneffei infection, CMV retinitis, or PML;
• Baseline CD4 T-lymphocyte count < 100 cells/μL;
• Planned initiation of antiretroviral therapy;
• Willing to participate in this study, able to comply with all follow-up requirements, and able to provide written informed consent.

Exclusion criteria

• Presence of Kaposi sarcoma, pregnancy, or confirmed tuberculosis;
• Body weight < 40 kg;
• Severe hepatic dysfunction (ALT or AST > 5 times the upper limit of normal, ULN);
• Severe renal dysfunction (eGFR < 30 mL/min/1.73 m²);
• Baseline electrocardiogram (ECG) showing a QTc interval > 500 ms;
• Pregnant or lactating women;
• Contraindications to glucocorticoid use;
• Any other condition considered by the investigators to be unsuitable for participation in this study.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Open label

Primary purpose

Prevention

Study locations

Center list to be confirmed — check the primary protocol.

Publications

• Meintjes G, Stek C, Blumenthal L, Thienemann F, Schutz C, Buyze J, Ravinetto R, van Loen H, Nair A, Jackson A, Colebunders R, Maartens G, Wilkinson RJ, Lynen L; PredART Trial Team. Prednisone for the Prevention of Paradoxical Tuberculosis-Associated IRIS. N Engl J Med. 2018 Nov 15;379(20):1915-1925. doi: 10.1056/NEJMoa1800762. PMID 30428290

Identifiers

NCT: NCT07565623 · 2025-S147-02

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗