Epstein-Barr virus

	Zambia HIV National Guidelines
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	Guide Editors
	Editor In Chief Joel E. Gallant, MD, MPH Pharmacology Editor Paul Pham, PharmD, BCPS Zambia Guideline Team Peter Mwaba MMed PhD FRCP Alywn Mwinga MMed Isaac Zulu MMed MPH Velepie Mtonga MMed Albert Mwango MBChB Jabbin Mulwanda MMed FCS

Epstein-Barr virus

Paul G. Auwaerter
08-17-2009

Zambia Specific Information

Nearly ubiquitous virus, acquired in childhood, so infectious mononucleosis probably rarely occurs in Zambia.
Role of EBV in HIV+ patients uncertain. Burkitt's lymphoma (BL) due to EBV common in East Africa, primarily as a childhood malignancy, without evident impact from HIV status. Unclear if HIV status is risk factor for BL in adults.
Role of EBV in both Hodgkin's Disease and non-Hodgkin's lymphoma (NHL) not well defined but most strongly associated with certain NHLs. One Tanzanian study of lymphoma found EBV present in 72% of tissues (including both HIV positive and negative patients).

Zambia Information Author: Paul Auwaerter, M.D.

Member of human gamma herpesvirus family. 90-95% in US infected by adult years. Most HIV+ individuals also harbor EBV.
Establishes latent infection. Spread mostly by asymptomatic shedding of virus into salivary secretions.
Primary infection = subclinical or infectious mononucleosis (IM); peak incidence of IM in teens and early 20's.
Presence of EBV may be considered as a tumor marker in proper clinical context.

EBV infection established in most individuals prior to HIV infection.
EBV+ and HIV: >60x risk of non-Hodgkins lymphoma (NHL) over general population, though overall risk remains small.
In HIV, EBV most highly associated with Lymphoma, Primary CNS (PCNSL). EBV CSF PCR + in ~100%. Studies suggest CSF PCR equivalent to brain Bx (sensitivity 83-100%, specificity 93-100%).
Significance of EBV PCR in other tissues and fluids less certain, though described with smooth muscle tumors in HIV+ pts (see Suankraty ref). Clinical reliability depends on assay used.
Serum Monospot (heterophile antibodies) used to Dx IM (~90%), although additional 10% may require Dx through EBV-specific serology, e.g., EBV capsid IgM, IgG, and EBNA antibodies.
False positive Monospot may be caused by acute HIV infection, and Sx can be similar. If risk factors exist, consider testing IM suspects with HIV viral load assay (acute retroviral syndrome).
Role of EBV PCR (quantitative) of blood uncertain: conflicting data regarding correlation with risk of NHL.
Since EBV establishes latency within cells, eradication impossible.

HIV-related lymphomas: B cell lymphoma (~100% CNS, ~50% peripheral lymphomas associated w/ EBV), T/NK cell lymphoma (10-100% depending on histological grade), sporadic Burkitts lymphoma (~25%), primary effusion lymphoma (70-80%, but 100% also contain HHV-8). See Lymphoma, Non-Hodgkins (NHL), Lymphoma, Hodgkins, Lymphoma, Primary CNS (PCNSL).
Nasopharyngeal carcinoma.
Leiomyosarcoma: mainly in children.
Oral hairy leukoplakia (OHL): white/gray patches on lateral margins of tongue caused by intense lytic-phase replication of EBV. Patches may spread to other parts of tongue. DDx=thrush, squamous cell CA, leukoplakia. Dx by appearance and location, cannot scrape off, unlike Candida.
Infectious mononucleosis: cardinal triad of fever, lymphadenopathy and pharyngitis. Unclear if presentation of primary EBV infection different in setting of HIV. More details about IM found in Epstein-Barr virus ABX Guide module.

Oral Hairy Leukoplakia

Treatment usually unnecessary. ART preferred as means to improve immune system and control lytic-phase EBV replication.
Other options include cryotherapy, surgical removal and topical podophyllin with variable results.
Acyclovir 800 mg PO 5x/d for 2-3 wks can limit EBV replication and may improve appearances; however, lesions recur with stopping therapy. Other drugs likely to work include valacyclovir, valganciclovir and famciclovir.

Infectious Mononucleosis

IM usually self-limited < 3wks average, rest and supportive care.
Corticosteroids (prednisone 40-60 mg/d) indicated for airway obstruction, severe thrombocytopenia or hemolytic anemia. Some give for severe pharyngitis or constitutional Sx (controversial).
Acyclovir/ganciclovir: no role in IM. Reduces viral shedding in mouth, but no clinical benefit.
Ganciclovir employed by some for EBV CNS disease, but little data backing this practice.

Drug	Recommendations/Comments
Acyclovir	Acyclovir and other antivirals such as famciclovir, valacyclovir, foscarnet and val/ganciclovir can all limit acute phase replication and viral shedding. Can use to treat OHL, but will recur without treatment of immunosuppression.Clinical impact of these drugs on HIV-related lymphomas is uncertain.
Ganciclovir	Limited data suggestive ganciclovir lowers EBV viral load in vivo, especially for PCNSL, but clinical utility undefined.

Triantos D, Porter SR, Scully C, et al.; Oral hairy leukoplakia: clinicopathologic features, pathogenesis, diagnosis, and clinical significance.; Clin Infect Dis; 1997; Vol. 25; pp. 1392-6;
ISSN: 1058-4838;
PUBMED: 9431384
Rating: Basis for recommendation
Comments:OHL generally only seen in later HIV infection, and its presence predicts AIDS. Why OHL develops and whether EBV reactivates from latency or superinfection remain uncertain. Despite appearance of the tongue, OHL does not appear to be a premalignant lesion.

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