A Man with Headache and Covid-19

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When should ART be initiated in a patient with newly diagnosed AIDS and cryptococcal meningoencephalitis?

Human immunodeficiency virus (HIV)-positive immunocompromised patients are at an increased risk for opportunistic central nervous system infections, such as cryptococcal meningitis, cerebral toxoplasmosis, and tuberculous meningitis. Read the NEJM Case Records of the Massachusetts General Hospital here.

Clinical Pearls

Q: Describe a characteristic feature of cryptococcal meningitis.

A: Cryptococcal infection usually occurs in the presence of severe immunosuppression characteristic of advanced HIV type 1 infection (CD4+ T-cell count, <50) and is often associated with an elevated opening pressure on lumbar puncture.

Q: How is the elevated intracranial pressure associated with cryptococcal meningoencephalitis treated?

A: The mechanism that is most likely to cause intracranial hypertension in a patient with meningoencephalitis in the absence of obstructive hydrocephalus on computed tomography of the head is impaired cerebrospinal fluid (CSF) absorption within the arachnoid granulations. This type of intracranial hypertension is treated with CSF diversion by means of serial lumbar puncture.


Morning Report Questions

Q: What are the key steps for the management of AIDS-associated cryptococcal meningoencephalitis?

A: Management of AIDS-associated cryptococcal meningoencephalitis centers on four key steps. The first step is administration of antifungal therapy, which consists of amphotericin B and flucytosine for at least 2 weeks, followed by consolidation and maintenance therapy with fluconazole. The second step, and often one of the most challenging aspects, is management of the elevated intracranial pressure. The third step is evaluation for complications of AIDS and other opportunistic infections, such as tuberculosis, Mycobacterium avium complex, and cytomegalovirus. The fourth and final step in the management of AIDS-associated cryptococcal meningoencephalitis is determination of when to start antiretroviral therapy (ART).

Q: When should ART be initiated in a patient with newly diagnosed AIDS and cryptococcal meningoencephalitis?

A: ART is usually begun soon after a diagnosis of HIV is established, often on the same day the diagnosis is made, because of the personal and public health benefits of treatment. However, in patients with cryptococcal meningoencephalitis, a rare exception is made, because such patients have increased mortality associated with early initiation of ART that is attributed to immune reconstitution inflammatory syndrome. We know to delay ART initiation in such patients but do not know the optimal time for initiation. Department of Health and Human Services guidance specifies that ART should be initiated within 2 to 10 weeks after the start of antifungal treatment, which is a wide time frame.

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