What is the clinical presentation of leptomeningeal infection in Acquired Immune Deficiency Syndrome (AIDS)/Human Immunodeficiency Virus (HIV)?

From the Guidelines

Leptomeningeal infections in HIV/AIDS patients should be treated promptly with antimicrobial therapy tailored to the causative organism, with a focus on managing increased intracranial pressure and preventing immune reconstitution inflammatory syndrome, as highlighted in the 2016 Infectious Diseases Society of America (IDSA) clinical practice guideline 1.

Key Considerations

• The most common pathogens include Cryptococcus neoformans, Mycobacterium tuberculosis, and various bacteria.
• For cryptococcal meningitis, the recommended treatment is induction therapy with amphotericin B (0.7-1 mg/kg/day IV) plus flucytosine (100 mg/kg/day divided into four doses) for at least two weeks, followed by consolidation therapy with fluconazole 400-800 mg daily for 8 weeks, then maintenance with fluconazole 200 mg daily until immune reconstitution occurs.
• For tuberculous meningitis, a four-drug regimen of isoniazid (5 mg/kg/day), rifampin (10 mg/kg/day), pyrazinamide (15-30 mg/kg/day), and ethambutol (15-25 mg/kg/day) for 2 months, followed by isoniazid and rifampin for 7-10 months is recommended.
• Bacterial meningitis requires broad-spectrum antibiotics initially, with adjustment based on culture results.
• Alongside antimicrobial therapy, antiretroviral therapy (ART) is crucial but should be timed carefully to avoid immune reconstitution inflammatory syndrome.
• Supportive care including management of increased intracranial pressure is essential, as elevated intracranial pressure occurs in excess of 50% of patients with cryptococcal meningitis, and aggressive management has been shown to improve outcomes 1.

Diagnosis and Management

• Diagnosis requires laboratory analysis of CSF, with abnormal CSF being the hallmark of all meningitis.
• The presence of immunodiffusion or CF IgG antibody performed in an experienced laboratory is nearly as specific, but lacks sensitivity.
• Neuroimaging, preferably by gadolinium-enhanced MRI, can further support the diagnosis.
• Patients with leptomeningeal infections may develop with few or no signs and symptoms of a respiratory illness, highlighting the importance of considering CM in patients with recent endemic exposure who develop symptoms such as headache, altered mental status, and unexplained vomiting 1.

From the Research

Leptomeningeal Infection in AIDS/HIV

• Leptomeningeal infection, such as cryptococcal meningitis, is a significant cause of morbidity and mortality in patients with HIV/AIDS 2.
• The presentation of leptomeningeal infection in HIV/AIDS patients typically includes symptoms such as headache, fever, and cranial nerve abnormalities 2.
• Neuroimaging findings in HIV-associated cryptococcal meningitis can vary depending on the patient's immune status, with pseudocysts and lacunar ischemic lesions more common in patients not on antiretroviral therapy, and contrast-enhancing focal leptomeningeal and/or parenchymal lesions more common in patients undergoing immune reconstitution 3.

Treatment and Management

• The treatment of cryptococcal meningitis in HIV-infected patients typically involves a combination of amphotericin and flucytosine, followed by step-down therapy to fluconazole 2, 4.
• High-dose amphotericin B (1 mg/kg per day) plus flucytosine has been shown to be more rapidly fungicidal than standard-dose amphotericin B plus flucytosine 4.
• Immune reconstitution inflammatory syndrome (IRIS) is a potential complication of antiretroviral therapy in patients with HIV-associated cryptococcal meningitis, and can manifest as a paradoxical exacerbation of symptoms despite improvements in CD4 count and viral load 3, 5.
• The management of IRIS typically involves continuation of primary therapy against the offending pathogen, continuation of effective HAART, and judicious use of anti-inflammatory agents 5.