You are in: eMedicine Specialties > Neurology > Neurological Infections HIV-1 Associated CNS Conditions: MeningitisArticle Last Updated: Mar 20, 2007AUTHOR AND EDITOR INFORMATIONSection 1 of 10
  Author: Niranjan N Singh, MD, DNB, Fellow in Neurophysiology, Department of Neurology, St Louis University School of Medicine Niranjan N Singh is a member of the following medical societies: American Academy of Neurology Coauthor(s): Suur Biliciler, MD, Neuromuscular Fellow, Department of Neurology, Baylor College of Medicine; Florian P Thomas, MD, MA, PhD, Drmed, Director, Spinal Cord Injury Unit, St Louis Veterans Affairs Medical Center; Director, National MS Society Multiple Sclerosis Center; Associate Program Director, Professor, Department of Neurology and Psychiatry, Associate Professor, Institute for Molecular Virology, and Department of Molecular Microbiology and Immunology, St Louis University Editors: Marion Priscilla Short, MD, Assistant Professor, Departments of Neurology, Pediatrics, and Pathology, University of Chicago Hospitals and Clinics; Francisco Talavera, PharmD, PhD, Senior Pharmacy Editor, eMedicine; Richard J Caselli, MD, Professor, Department of Neurology, Mayo Medical School, Rochester, MN; Chair, Department of Neurology, Mayo Clinic of Scottsdale; Matthew J Baker, MD, Consulting Staff, Collier Neurologic Specialists, Naples Community Hospital; Nicholas Y Lorenzo, MD, Chief Editor, eMedicine Neurology; Consulting Staff, Neurology Specialists and Consultants Author and Editor Disclosure Synonyms and related keywords: acquired immunodeficiency syndrome, AIDS, cryptococcal meningitis, tuberculous meningitis, syphilitic meningitis, Listeria species, lymphomatous meningitis, aseptic meningitis, cryptococcosis, coccidioidomycosis, histoplasmosis, CMV, cytomegalovirus, CNS infections in HIV, Listeria monocytogenes, histoplasmosis, syphilis, tuberculosis, CNS syphilis, bacterial meningitis INTRODUCTIONSection 2 of 10
  BackgroundDifferent forms of meningitis are associated with HIV infection. They may be classified according to the etiologic agent as cryptococcal, tuberculous, syphilitic, or Listeria species; others are lymphomatous or aseptic. PathophysiologyMeningitis is multifactorial in patients with HIV/AIDS. Besides specific pathogens, autoimmune processes and HIV itself have been implicated. Although HIV-seropositive individuals are at increased risk of certain types of meningitis, evidence suggests that they are also more likely than the general population to develop community-acquired bacterial or viral meningitides. An early form of aseptic, HIV-associated meningitis develops within days to weeks after HIV infection. It appears as a mononucleosis-like illness and is rarely associated with encephalitis. Meningitides due to cryptococcosis, coccidioidomycosis, histoplasmosis, or other fungal infection are AIDS-defining events and occur typically with very low CD4+ lymphocyte counts. Chronic meningitis or episodes of acute meningitis for which no cause is found can occur anytime during the disease course. An asymptomatic form is found in one third of patients in whom CSF is examined for other reasons (eg, headache). Cytomegaloviral (CMV) infection usually presents as an encephaloventriculitis with possible meningeal involvement. Medications as causes are often overlooked including nonsteroidal anti-inflammatory drugs (NSAIDs), trimethoprim/sulfamethoxazole, and intravenous immunoglobulin (IVIG). In patients receiving highly active anti-retroviral therapy (HAART) and a syndrome of relapsing remitting meningitis with negative cultures and atypical signs and symptoms, consider immune reconstitution inflammatory syndrome (IRIS). This is regarded as an overactive response of a newly reconstituted immune system to infectious agents already present in the patient when the therapy is started. Symptoms that are consistent with an infectious and/or inflammatory condition appear while the patient is on antiretroviral therapy and the symptoms cannot be explained by a new or a previous infection or by the side effects of the therapy. It has been proposed that IRIS is due to an imbalance of CD8+/CD4+ cells. FrequencyUnited StatesCryptococcal meningitis is the most common opportunistic infection of the CNS, affecting 5-7% of patients with AIDS. The second most common type of meningitis is aseptic meningitis, which may be caused by HIV-1 itself. Rarer CNS infections are due to Listeria monocytogenes, coccidioidomycosis, histoplasmosis, syphilis, and tuberculosis. CNS syphilis may occur earlier and more frequently in HIV-seropositive individuals than in HIV-seronegative individuals. Bacterial meningitis often occurs in conjunction with sepsis due to the same organism. In rare cases, metastatic CNS lymphoma can appear as meningitis. Mortality/MorbidityMortality rates and morbidity vary by the etiology of meningitis. A previously reported mortality rate of 20% for cryptococcal meningitis, for example, may now be as low as 6% owing to more aggressive therapy. Higher mortality rates correlate with poor mental status, high CSF opening pressure at presentation, positive India ink test, extra-CNS manifestations, and higher fungal burdens. CLINICALSection 3 of 10
HistoryIn general, symptoms and signs typically associated with meningitis are less likely to occur in HIV-seropositive individuals than in the general population. This probably reflects the different organisms involved and the differences in immune responses. One meta-analysis showed that stiff neck occurred in 50% of cases of non-AIDS meningitis; four studies shoed rates of 22%, 31%, 37%, and 44% for AIDS meningitis. Similarly, the frequency of papilledema was 28% in that same study of non-AIDS meningitis, whereas frequencies of 6% and 8% were reported in 2 studies of AIDS meningitis. Characteristics of HIV-seropositive patients with meningitis are the following:
Physical
DIFFERENTIALSSection 4 of 10
Chronic Paroxysmal Hemicrania Headache: Pediatric Perspective Meningococcal Meningitis Migraine Headache Neurosyphilis Staphylococcal Meningitis
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| Drug Name | Ganciclovir (Cytovene, Vitrasert) |
|---|---|
| Description | Synthetic guanine derivative active against CMV. Acyclic nucleoside analog of 2'-deoxyguanosine that inhibits replication of herpesviruses in vitro and in vivo. Levels of ganciclovir triphosphate are as much as 100-fold greater in CMV-infected cells than in uninfected cells, possibly because of preferential phosphorylation of ganciclovir in virus-infected cells. In patients who with progression of CMV retinitis while receiving maintenance treatment with either form, induction regimen should be readministered. |
| Adult Dose | Induction: 5 mg/kg IV bid for 14 d Maintenance: 5 mg/kg/d IV for 5-7 d, then 500 mg PO q4h or 1 g PO tid for life |
| Pediatric Dose | Not established for congenital/neonatal infection |
| Contraindications | Documented hypersensitivity; thrombocytopenia (platelets <25 x 109/L); neutropenia (ANC <500/µL) |
| Interactions | Concomitant administration of cytotoxic drugs (eg, dapsone, vinblastine, doxorubicin, pentamidine, flucytosine, vincristine, amphotericin B, trimethoprim/sulfamethoxazole combinations, other nucleoside analogs) may result in additive toxicity in bone marrow, spermatogonium, and germinal layers of skin and GI mucosa (coadminister only if potential benefits outweigh risks); coadministration with imipenem-cilastatin may cause generalized seizures (use only if potential benefits outweigh risks); serum creatinine may increase after use of cyclosporine or amphotericin B; probenecid reduces renal clearance; bioavailability may increase when didanosine administered simultaneously or 2 h before; zidovudine may decrease bioavailability, whereas ganciclovir increases bioavailability of zidovudine |
| Pregnancy | D - Unsafe in pregnancy |
| Precautions | Clinical toxic effects include granulocytopenia, anemia, and thrombocytopenia; oral form (vs IV form) associated with increased rate of CMV retinitis progression, use oral form only when benefits outweigh risks (eg, advanced HIV disease); half-life and plasma or serum concentrations may be increased due to reduced renal clearance; dosages > 6 mg/kg IV may result in increased toxicity; rapid infusions may result in increased toxicity; reconstituted solutions of IV form have high pH (pH 11); phlebitis or pain may occur at site of IV infusion despite further dilution in IV fluids; administration should be accompanied by adequate hydration; photosensitization (photoallergy or phototoxicity) may occur |
| Drug Name | Foscarnet (Foscavir) |
|---|---|
| Description | Organic analog of inorganic pyrophosphate that inhibits replication of known herpesviruses, including CMV, HSV-1, and HSV-2. Inhibits viral replication at pyrophosphate-binding site on virus-specific DNA polymerases. Poor clinical response or persistent viral excretion during therapy may be due to viral resistance. Patients who can tolerate foscarnet well may benefit from early maintenance treatment at 120 mg/kg/d. Individualize dosing to renal function. |
| Adult Dose | 60 mg/kg IV tid for 14 d, then 90-120 mg/kg IV qd for life |
| Pediatric Dose | <12 years: Not established >12 years: Administer as in adults |
| Contraindications | Documented hypersensitivity |
| Interactions | Avoid use in combination with potentially nephrotoxic drugs (eg, aminoglycosides, amphotericin B, IV pentamidine) unless potential benefits outweigh risks; coadministration with IV pentamidine may cause hypocalcemia |
| Pregnancy | C - Safety for use during pregnancy has not been established. |
| Precautions | May cause decline in renal function; for correct dosing, obtain 24-h urine with CrCl at baseline and thereafter (discontinue if CrCl <0.4 mL/min/kg); hydration may reduce nephrotoxicity; carefully monitor electrolytes (eg, Ca, Mg); assess for electrolyte and mineral abnormalities if mild perioral numbness, paresthesias, or seizures occur; granulocytopenia and anemia may occur (monitor CBC regularly); infuse into veins with adequate blood flow to avoid local irritation; to avoid toxicity, do not administer by rapid or bolus IV injection |
These agents treat systemic fungal infections, such as cryptococcal meningitis.
| Drug Name | Amphotericin B, conventional (Amphocin, Fungizone) |
|---|---|
| Description | Produced by strain of Streptomyces nodosus; can be fungistatic or fungicidal. Binds to sterols, such as ergosterol, in the fungal cell membrane, causing intracellular components to leak and subsequent fungal cell death. |
| Adult Dose | 0.7-1 mg/kg/d IV; total cumulative dose is 3 g Combination therapy: 0.7-1 mg/kg/d amphotericin B IV and 100 mg/kg/d flucytosine PO for 2 wk |
| Pediatric Dose | Not established; recommended dose 0.5 mg/kg/d IV |
| Contraindications | Documented hypersensitivity |
| Interactions | Antineoplastic agents may enhance potential of amphotericin B for renal toxicity, bronchospasm, and hypotension; corticosteroids, digitalis, and thiazides may potentiate hypokalemia; risk of renal toxicity increased with cyclosporine |
| Pregnancy | C - Safety for use during pregnancy has not been established. |
| Precautions | Monitor renal function, serum electrolyte (eg, Mg, K) concentrations, liver functions, CBC, and hemoglobin; resume at lowest level (eg, 0.25 mg/kg) if interrupted for <7 d; hypoxemia, acute dyspnea, and interstitial infiltrates may occur in neutropenic patients receiving leukocyte transfusions (separate amphotericin infusion from transfusion in time) |
| Drug Name | Flucytosine (Ancobon) |
|---|---|
| Description | Converted to fluorouracil after penetrating fungal cells, inhibiting RNA and protein synthesis. Active against Candida and Cryptococcus species and generally used in combination with amphotericin B. |
| Adult Dose | 100 mg/kg PO qd for 2 wk Combination therapy: 0.7-1 mg/kg/d amphotericin B IV and 100 mg/kg/d flucytosine PO for 2 wk |
| Pediatric Dose | Not established; suggested dose 200 mg/kg IV qd |
| Contraindications | Documented hypersensitivity |
| Interactions | Toxicity may be increased by amphotericin B; may be inactivated by cytosine |
| Pregnancy | C - Safety for use during pregnancy has not been established. |
| Precautions | Caution in bone marrow suppression; adjust dose in renal impairment |
| Drug Name | Fluconazole (Diflucan) |
|---|---|
| Description | Synthetic oral antifungal (broad-spectrum bistriazole) that selectively inhibits fungal cytochrome P-450 and sterol C-14 alpha-demethylation. Achieves responses similar to amphotericin but has higher rate of early mortality. |
| Adult Dose | 400 mg PO qd for 10 wk, then 200 mg PO qd for life |
| Pediatric Dose | 2-3 mg/kg PO qd |
| Contraindications | Documented hypersensitivity |
| Interactions | Levels may increase with hydrochlorothiazides; levels may decrease with long-term rifampin; may decrease phenytoin concentrations; may increase concentrations of theophylline, tolbutamide, glyburide, and glipizide; may increase effects of anticoagulants; may increase cyclosporine concentrations |
| Pregnancy | C - Safety for use during pregnancy has not been established. |
| Precautions | Monitor closely if rashes develop and discontinue drug if lesions progress; may cause clinical hepatitis, cholestasis, and fulminant hepatic failure (including death) in patients with underlying medical conditions such as AIDS or a malignancy and in those taking multiple concomitant medications; not recommended for nursing mothers; regarding single-dose use, convenience and efficacy of single-dose regimen for vaginal yeast infections should be weighed against difficulties from increased incidence of adverse reactions reported with oral fluconazole than with intravaginal agents; use in nursing mothers not recommended; use in pregnancy only if benefits outweigh risks |
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HIV-1 Associated CNS Conditions: Meningitis excerpt
Article Last Updated: Mar 20, 2007
