In an HIV‑positive adult with cryptococcal meningitis, should antiretroviral therapy be held during the initial antifungal induction phase or continued?

Management of ART in Cryptococcal Meningitis IRIS

If IRIS develops in a patient with cryptococcal meningitis who is already on ART, continue both antiretroviral therapy and antifungal therapy without interruption. 1

Core Management Principle for Established IRIS

The fundamental approach when IRIS occurs is straightforward:

• Continue ART without interruption - stopping antiretroviral therapy provides no benefit and may worsen long-term outcomes 1
• Continue antifungal therapy - maintain the current antifungal regimen as planned 1
• Manage IRIS symptoms supportively rather than by modifying the underlying therapies 2

Symptomatic Management of IRIS

For patients experiencing severe IRIS symptoms:

• Short-course corticosteroids are recommended by specialists for severely symptomatic IRIS 1
• Aggressive management of elevated intracranial pressure is critical if present - this includes daily lumbar punctures to reduce opening pressure 1, 2
• Anti-inflammatory medications can provide symptomatic relief 2

Critical Distinction: Prevention vs. Treatment

The evidence clearly distinguishes between preventing IRIS (by delaying ART initiation) versus treating established IRIS (by continuing ART):

For Prevention (ART-naive patients):

• Delay ART initiation for at least 2 weeks after starting antifungal therapy, potentially up to 4-5 weeks for severe disease or elevated intracranial pressure 1, 3
• A landmark randomized trial demonstrated that deferring ART to 5 weeks resulted in 45% mortality with early ART (1-2 weeks) versus 30% mortality with deferred ART (5 weeks), with excess deaths occurring 2-5 weeks after diagnosis 4
• This delay allows time for control of intracranial pressure and reduction of fungal burden 3, 2

For Established IRIS:

• No role for ART interruption once IRIS develops 2
• Stopping ART increases mortality risk in cryptococcal meningitis 2

Understanding the Epidemiology

Approximately 30% of patients with cryptococcal meningitis and HIV infection will experience IRIS after ART initiation or reinitiation 1. Risk factors include:

• Being antiretroviral-naive at diagnosis 1
• Higher baseline HIV RNA levels 1
• Low CSF white cell counts (<5 cells/mm³) at presentation 4

Common Pitfalls to Avoid

• Do not stop ART when IRIS develops - this is a common error that worsens outcomes 1, 2
• Do not use corticosteroids routinely - steroids should only be used for specific indications (severe IRIS or cryptococcoma with cerebral edema and herniation risk), as routine steroid use increases mortality 2
• Do not neglect intracranial pressure management - elevated opening pressure is present in up to 75% of patients and accounts for 93% of deaths in the first 2 weeks 1

Monitoring Requirements

When managing IRIS in cryptococcal meningitis:

• Serial lumbar punctures with opening pressure measurement if symptoms of elevated intracranial pressure develop 1
• Clinical monitoring for neurologic deterioration, confusion, blurred vision, papilledema, or lower extremity clonus 1
• Consider CSF shunting if daily lumbar punctures are no longer tolerated or fail to relieve symptoms of cerebral edema 1