Immune reconstitution inflammatory syndrome (IRIS)
Immune reconstitution inflammatory syndrome (IRIS) is a paradoxical worsening or unmasking of an infection that follows antiretroviral therapy (ART) in a patient with advanced HIV, most often when the pretreatment CD4 count is under 100 cells per microliter. Diagnosis is clinical, made by excluding treatment failure, a new infection, and a drug reaction. Management continues ART and treats the underlying pathogen, adding NSAIDs or glucocorticoids for symptomatic disease.
- Topic reviewThe full article, organized the way the exam asks it.
- ABIM-format MCQsVignettes with an explanation for every wrong answer.
- Key factsThe numbers and thresholds worth memorizing, up front.
- AI tutorMedBrain answers the question you're stuck on.
What this article covers
- Overview
Immune reconstitution inflammatory syndrome (IRIS) is a paradoxical clinical worsening of a known infection, or the unmasking of one that was previously subclinical, that follows the start or…
- Epidemiology
Who develops it: IRIS occurs in patients with advanced HIV who start or restart ART, most often those with a pretreatment helper T-lymphocyte (CD4) count under 100 cells/microliter, the threshold most consistently linked to risk.
- Risk factors
Low pretreatment CD4 count: a CD4 count below 100 cells/microliter before starting ART is the strongest and most reproducible risk factor.
- Pathophysiology
Restored pathogen-specific immunity: ART suppresses HIV replication and allows recovery of pathogen-specific CD4 and CD8 T-lymphocyte responses that had been blunted by HIV-driven immunosuppression.
- Clinical features
Timing: paradoxical IRIS most often develops within days to a few months of starting ART, while unmasking IRIS can present later as previously silent disease becomes symptomatic.
- Differential diagnosis
Treatment failure from drug-resistant or undertreated infection: the treated pathogen persists or grows on repeat culture, unlike IRIS, in which cultures are typically sterile or improving and the worsening tracks a rising CD4 count.
- Diagnosis
The diagnosis is established clinically, by exclusion: new or worsening inflammatory findings in a patient with confirmed HIV infection who started or restarted ART in the preceding weeks to months…
- Management
First, continue ART without interruption in nearly all cases, and continue or start pathogen-specific therapy for the underlying infection, since stopping ART removes the drive to clear the organism…
- Complications
Airway compromise: massive cervical or mediastinal lymphadenopathy in TB-IRIS can compress the airway, occurring most often in the first weeks after ART is started.
- Prognosis
Most cases are self-limited: symptoms typically resolve over weeks to a few months with continued ART, pathogen-specific therapy, and anti-inflammatory treatment when needed.
- Prevention
Screen for subclinical infection before starting ART: in patients with a CD4 count below 100 cells/microliter, screen for cryptococcal antigenemia and active TB before ART is started to reduce unmasking IRIS.
Read the whole article
Subscribing to Internal Medicine opens every article, the full question bank and MedBrain, on the web, iPhone and Android.
Related articles
- HIV antiretroviral therapy (ART)
Antiretroviral therapy (ART) combines three or more drugs from at least two classes to suppress HIV replication. First-line therapy is bictegravir/emtricitabine/tenofovir alafenamide or dolutegravir-based triple therapy, started as soon as the patient is ready regardless of CD4 count, and continued for life to prevent AIDS and transmission.
- Tuberculosis
Tuberculosis, caused by Mycobacterium tuberculosis, remains a leading global cause of infectious death and presents as latent infection, primary/secondary pulmonary disease, or extrapulmonary and disseminated (miliary) disease. Diagnosis rests on AFB smear, NAAT, and mycobacterial culture (the gold standard), and drug-susceptible active disease is treated with a four-drug regimen (isoniazid, rifampin, pyrazinamide, ethambutol) for 2 months followed by isoniazid plus rifampin for 4 to 7 months.
- Cryptococcal meningoencephalitis
Cryptococcal meningoencephalitis is the most common cause of fungal meningitis worldwide, driven by CNS dissemination of inhaled Cryptococcus in an immunosuppressed host, typically HIV with a CD4 count under 50; treatment is induction amphotericin B plus flucytosine, consolidation and maintenance fluconazole, and aggressive lowering of elevated intracranial pressure.
- Toxoplasmosis
Toxoplasmosis is infection with the protozoan Toxoplasma gondii, acquired from undercooked meat or cat feces, causing a mononucleosis-like illness in immunocompetent hosts, reactivation encephalitis with ring-enhancing brain lesions in advanced HIV, and a severe congenital syndrome after maternal primary infection in pregnancy. Diagnosis in CNS disease is largely presumptive on serology, imaging, and empiric treatment response, and management is pyrimethamine-sulfadiazine-leucovorin, with prevention centered on CD4-based prophylaxis and food/cat-litter precautions in pregnancy.
- Progressive multifocal leukoencephalopathy
Progressive multifocal leukoencephalopathy is an opportunistic demyelinating brain infection caused by reactivation of JC virus in significantly immunosuppressed patients, most often with AIDS or on natalizumab, rituximab, or other immunomodulators. Diagnosis rests on MRI white matter lesions plus CSF JC virus PCR; there is no antiviral treatment, so management is restoring immune function.
- Kaposi sarcoma
Kaposi sarcoma is a human herpesvirus 8-associated vascular malignancy that presents as violaceous macules, papules, plaques, or tumors of the skin, mouth, gastrointestinal tract, or lungs, most often in HIV-associated, transplant-related, or classic elderly disease. Diagnosis is confirmed by biopsy. Every patient with HIV-associated Kaposi sarcoma starts or optimizes antiretroviral therapy, with liposomal doxorubicin 20 mg/m2 intravenously every 21 days added for extensive or visceral disease.
- Acute HIV infection
Acute HIV infection, also called the acute retroviral syndrome, is the symptomatic viremic phase in the days to weeks after HIV acquisition, presenting with fever, fatigue, myalgia, rash, and pharyngitis at a time when antibody testing may still be negative. Diagnosis requires an HIV RNA viral load, and antiretroviral therapy should begin as soon as the patient is ready, regardless of CD4 count.