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Human herpesvirus-8 (HHV-8) seroprevalence among the general population in the United States is 1%-5%. The seroprevalence is greater among MSM (20%-77%) (800Corey L, Pauk J, Wald A. Mucosal shedding of human herpesvirus 8 in men. N Engl J Med 2001;344:691-2.), regardless of HIV infection, and is also higher in certain Mediterranean countries (10%-20%) and in parts of sub-Saharan Africa (30%-80%). HHV-8 is associated with all forms of KS (i.e., classic, endemic, transplant-related, and AIDS-related) and certain rare neoplastic (e.g., primary effusion lymphoma [PEL]) and lymphoproliferative disorders (multicentric Castleman disease [MCD]). The precise pathogenesis is unclear even though seroconversion to HHV-8 precedes the development of these tumors (786Gao SJ, Kingsley L, Hoover DR, et al. Seroconversion to antibodies against Kaposi's sarcoma-associated herpesvirus-related latent nuclear antigens before the development of Kaposi's sarcoma. N Engl J Med 1996;335:233-41.). Patients who are HHV-8 seropositive and have HHV-8 viremia have an increased risk (approximately ninefold) for experiencing KS compared with HHV-8 seropositive men without HHV-8 viremia (787Lennette ET, Blackbourn DJ, Levy JA. Antibodies to human herpesvirus type 8 in the general population and in Kaposi's sarcoma patients. Lancet 1996;348:858-61.), and HHV-8 viremia almost always accompanies symptomatic episodes of MCD (788Oksenhendler E, Carcelain G, Aoki Y, et al. High levels of human herpesvirus 8 viral load, human interleukin-6, interleukin-10, and C reactive protein correlate with exacerbation of multicentric castleman disease in HIV-infected patients. Blood 2000;96:2069-73.).

The overall incidence of KS was as high as 20% among patients with AIDS before the advent of effective ART. However, even before the widespread use of ART, the incidence had declined, perhaps because of ganciclovir, foscarnet, and cidofovir use for treatment of CMV disease. These agents inhibit the replication of HHV-8 in vitro, (789Cannon JS, Hamzeh F, Moore S, Nicholas J, Ambinder RF. Human herpesvirus 8-encoded thymidine kinase and phosphotransferase homologues confer sensitivity to ganciclovir. J Virol 1999;73:4786-93., 790Neyts J, De Clercq E. Antiviral drug susceptibility of human herpesvirus 8. Antimicrob Agents Chemother 1997;41:2754-6., 803Casper C, Wald A. The use of antiviral drugs in the prevention and treatment of Kaposi sarcoma, multicentric Castleman disease and primary effusion lymphoma. Curr Top Microbiol Immunol 2007;312:289-307.) and observational studies indicate that patients receiving ganciclovir or foscarnet (but not acyclovir) develop KS at a reduced rate (710Martin DF, Kuppermann BD, Wolitz RA, Palestine AG, Li H, Robinson CA. Oral ganciclovir for patients with cytomegalovirus retinitis treated with a ganciclovir implant. N Engl J Med 1999;340:1063-70., 791Ioannidis JP, Collier AC, Cooper DA, et al. Clinical efficacy of high-dose acyclovir in patients with human immunodeficiency virus infection: a meta-analysis of randomized individual patient data. J Infect Dis 1998; 178:349-59., 792Mocroft A, Youle M, Gazzard B, et al. Anti-herpesvirus treatment and risk of Kaposi's sarcoma in HIV infection. AIDS 1996;10:1101-5., 793Glesby MJ, Hoover DR, Weng S, et al. Use of antiherpes drugs and the risk of Kaposi's sarcoma: data from the Multicenter AIDS Cohort Study. J Infect Dis 1996; 173:1477-80.). The incidence of KS has declined after the introduction of PIs and HAART (794Eltom MA, Jemal A, Mbulaiteye SM, Devesa SS, Biggar RJ. Trends in Kaposi's sarcoma and non-Hodgkin's lymphoma incidence in the United States from 1973 through 1998. J Natl Cancer Inst 2002;94:1204-10.). PEL and MCD remain rare (795Casper C. The aetiology and management of Castleman disease at 50 years: translating pathophysiology to patient care. Br J Haematol 2005;129:3-17.).

KS and PEL are described most frequently among HIV-infected persons with more advanced immunosuppression (CD4⁺ counts of <200 cells/µL), although they can occur at any CD4⁺ count. Episodes of MCD might present at any CD4⁺ count.

Most persons with chronic HHV-8 infection are asymptomatic (796Casper C, Krantz E, Selke S, et al. Frequent and asymptomatic oropharyngeal shedding of human herpesvirus 8 among immunocompetent men. J Infect Dis 2007;195:30-6.). Acquisition of HHV-8 has been associated with a primary infection syndrome consisting of fever, rash, lymphadenopathy, bone marrow failure, and occasional rapid progression to KS (797Andreoni M, Sarmati L, Nicastri E, et al. Primary human herpesvirus 8 infection in immunocompetent children. JAMA 2002;287:1295-300., 798Luppi M. Bone marrow failure associated with human herpesvirus 8 infection after transplantation. N Engl J Med 2000;343:1378-85.). MCD manifests with generalized adenopathy and fever and can progress to multi-organ failure (795Casper C. The aetiology and management of Castleman disease at 50 years: translating pathophysiology to patient care. Br J Haematol 2005;129:3-17.). KS symptoms vary widely, but most persons have nontender, purplish, indurated skin lesions. Intraoral lesions are common and visceral dissemination can occur, occasionally without the presence of skin lesions. Other manifestations of HHV-8 infection are beyond the scope of this report. Asymptomatic HHV-8 infection is often associated with HHV-8 shedding in the saliva and occasional shedding in genital secretions (796Casper C, Krantz E, Selke S, et al. Frequent and asymptomatic oropharyngeal shedding of human herpesvirus 8 among immunocompetent men. J Infect Dis 2007;195:30-6., 799Casper C, Redman M, Huang ML, et al. HIV infection and human herpesvirus-8 oral shedding among men who have sex with men. J Acquir Immune Defic Syndr 2004;35:233-8., 800Corey L, Pauk J, Wald A. Mucosal shedding of human herpesvirus 8 in men. N Engl J Med 2001;344:691-2.); viral shedding might result in HHV-8 transmission to uninfected partners.

Routine screening for HHV-8 by PCR or serologic testing for HHV-8 antibody is not indicated for HIV-infected persons. Use of PCR to quantify HHV-8 in the peripheral blood is helpful in the diagnosis and management of persons with MCD (788Oksenhendler E, Carcelain G, Aoki Y, et al. High levels of human herpesvirus 8 viral load, human interleukin-6, interleukin-10, and C reactive protein correlate with exacerbation of multicentric castleman disease in HIV-infected patients. Blood 2000;96:2069-73.).

Recommendations related to preventing exposure to HHV-8 do not exist.

Despite observational evidence supporting a role for anti-HHV-8 therapy in preventing the development of KS, the toxicity of current anti-HHV-8 therapy outweighs the potential benefits of administration (DIII).

Although ganciclovir, foscarnet, and cidofovir have in vitro activity against HHV-8, and limited studies indicate these agents might be associated with reduced KS disease progression or lesion regression, larger and more definitive studies are needed to determine whether antiviral therapy has a useful role in managing HHV-8-associated diseases. KS regression has been documented after ganciclovir or foscarnet therapy (801-803), although one study indicated cidofovir was ineffective (804Little RF, Merced-Galindez F, Staskus K, et al. A pilot study of cidofovir in patients with kaposi sarcoma. J Infect Dis 2003;187:149-53.). The use of IV ganciclovir or oral valganciclovir is, however, recommended in the treatment of MCD (BII) (805Casper C, Nichols WG, Huang ML, Corey L, Wald A. Remission of HHV-8 and HIV-associated multicentric Castleman disease with ganciclovir treatment. Blood 2004;103:1632-4.) and might be useful adjunctive therapy in the treatment of PEL (BII) (806Aboulafia DM. Interleukin-2, ganciclovir, and high-dose zidovudine for the treatment of AIDS-associated primary central nervous system lymphoma. Clin Infect Dis 2002;34:1660-2., 807Crum-Cianflone NF, Wallace MR, Looney D. Successful secondary prophylaxis for primary effusion lymphoma with human herpesvirus 8 therapy. AIDS 2006;20:1567-9.). Highly active ART that suppresses HIV replication should be administered to all HIV-infected persons with KS, PEL, or MCD (BII), although insufficient evidence exists to support using one HAART regimen over another. Chemotherapy, in combination with ART, should be considered for patients with PEL or visceral KS (BII) and might be a useful adjunctive therapy in persons with widely disseminated cutaneous KS (CIII). Rituximab also appears to be an effective alternative to antiviral therapy in the treatment of MCD (BII) (808Marcelin AG, Aaron L, Mateus C, et al. Rituximab therapy for HIV-associated Castleman disease. Blood 2003;102:2786-8.).

Fatal IRIS has been reported in persons initiating ART with pre-existing KS and MCD. The frequency of HHV-8-associated IRIS is not known but suppression of HIV replication and immune reconstitution are key components of therapy and initiation of ART should not be delayed.

Effective suppression of HIV replication with ART among HIV-infected patients with KS might prevent KS progression or occurrence of new lesions and should be considered for all persons with evidence of active KS (BII). Suppression of HIV replication also is recommended for persons with MCD (BII) and those with malignant lymphoproliferative disorders.

The seroprevalence of HHV-8 infection among HIV-infected pregnant women varies by geographic area, ranging from 1.7% among U.S.-born and 3.6% among Haitian-born women in New York City to 11.6% among pregnant women from four other U.S. cities (809Goedert JJ, Kedes DH, Ganem D. Antibodies to human herpesvirus 8 in women and infants born in Haiti and the USA. Lancet 1997;349:1368.). Pregnancy does not appear to affect the prevalence of antibodies to HHV-8 or the antibody levels (84Huang LM, Huang SY, Chen MY, et al. Geographical differences in human herpesvirus 8 seroepidemiology: a survey of 1,201 individuals in Asia. J Med Virol 2000;60:290-3.), although levels of HHV-8 DNA in the peripheral blood might increase late in pregnancy (810Lisco A, Barbierato M, Fiore JR, et al. Pregnancy and human herpesvirus 8 reactivation in human immunodeficiency virus type 1-infected women. J Clin Microbiol 2006;44:3863-71.). HHV-8 seropositivity does not appear to influence pregnancy outcome. Routine screening for HHV-8 by PCR or serology is not indicated for HIV-infected pregnant women (DII). In vitro models suggest that beta-human chorionic gonadotropin induces regression of KS tumors, but clinical reports on the incidence and natural history of KS in pregnancy are conflicting (811Berger P, Dirnhofer S. Kaposi's sarcoma in pregnant women. Nature 1995;377:21-2., 812Lunardi-Iskandar Y, Bryant JL, Zeman RA, et al. Tumorigenesis and metastasis of neoplastic Kaposi's sarcoma cell line in immunodeficient mice blocked by a human pregnancy hormone. Nature 1995;375:64-8., 813Rabkin CS, Chibwe G, Muyunda K, Musaba E. Kaposi's sarcoma in pregnant women. Nature 1995;377:21., 814Schulz TF, Weiss RA. Kaposi's sarcoma. A finger on the culprit. Nature 1995;373:17-8.)

Diagnosis of KS or other HHV-8-associated neoplasms in pregnancy should be the same as in nonpregnant women. Recommendations for the treatment of HHV-8 malignancies are beyond the scope of these guidelines. Treatment should be undertaken in consultation with a specialist.

Perinatal transmission of HHV-8 might occur infrequently. Evidence supporting vertical transmission during pregnancy or the intrapartum period includes cases of KS occurring in the infant shortly after birth (815Gutierrez-Ortega P, Hierro-Orozco S, Sanchez-Cisneros R, Montao LF. Kaposi's sarcoma in a 6-day-old infant with human immunodeficiency virus. Arch Dermatol 1989;125:432-3., 816McCarthy GA, Kampmann B, Novelli V, et al. Vertical transmission of Kaposi's sarcoma. Arch Dis Child 1996;74:455-7.), higher risk for transmission with higher maternal antibody titer (and by inference higher maternal levels of HHV-8) (817Sitas F, Newton R, Boschoff C. Increasing probability of mother-to-child transmission of HHV-8 with increasing maternal antibody titer for HHV-8. N Engl J Med 1999;340:1923.), and detection of similar strains of HHV-8 DNA by PCR in specimens drawn at birth from HHV-8-seropositive mothers and their infants (818Mbulaiteye S, Marshall V, Bagni RK, et al. Molecular evidence for mother-to-child transmission of Kaposi sarcoma-associated herpesvirus in Uganda and K1 gene evolution within the host. J Infect Dis 2006;193:1250-7.). Data indicate increased mortality through age 24 months among HIV-infected infants born to HHV-8-seropositive compared with HHV-8-seronegative mothers (815Gutierrez-Ortega P, Hierro-Orozco S, Sanchez-Cisneros R, Montao LF. Kaposi's sarcoma in a 6-day-old infant with human immunodeficiency virus. Arch Dermatol 1989;125:432-3., 816McCarthy GA, Kampmann B, Novelli V, et al. Vertical transmission of Kaposi's sarcoma. Arch Dis Child 1996;74:455-7., 817Sitas F, Newton R, Boschoff C. Increasing probability of mother-to-child transmission of HHV-8 with increasing maternal antibody titer for HHV-8. N Engl J Med 1999;340:1923., 819Mantina H, Kankasa C, Klaskala W, et al. Vertical transmission of Kaposi's sarcoma-associated herpesvirus. Int J Cancer 2001;94:749-52., 820Serraino D, Locatelli M, Songini M, et al. Human herpes virus-8 infection among pregnant women and their children: results from the Sardinia-IDDM Study 2. Int J Cancer 2001;91:740-1., 821Gessain A, Mauclere P, van Beveren M, et al. Human herpesvirus 8 primary infection occurs during childhood in Cameroon, Central Africa. Int J Cancer 1999;81:189-92., 822Bourboulia D, Whitby D, Boshoff C, et al. Serologic evidence for mother-to-child transmission of Kaposi sarcoma-associated herpesvirus infection. JAMA 1998;280:31-2., 823Whitby D, Smith NA, Matthews S, et al. Human herpesvirus 8: seroepidemiology among women and detection in the genital tract of seropositive women. J Infect Dis 1999;179:234-6., 824Plancoulaine S, Abel L, van Beveren M, et al. Human herpesvirus 8 transmission from mother to child and between siblings in an endemic population. Lancet 2000;356:1062-5.), but these studies could not completely account for other confounding factors affecting HIV-infected infants. The majority of studies document a substantially higher rate of HHV-8 seropositivity among children born to HHV-8 antibody-positive compared with HHV-8 antibody-negative women (819Mantina H, Kankasa C, Klaskala W, et al. Vertical transmission of Kaposi's sarcoma-associated herpesvirus. Int J Cancer 2001;94:749-52., 820Serraino D, Locatelli M, Songini M, et al. Human herpes virus-8 infection among pregnant women and their children: results from the Sardinia-IDDM Study 2. Int J Cancer 2001;91:740-1., 821Gessain A, Mauclere P, van Beveren M, et al. Human herpesvirus 8 primary infection occurs during childhood in Cameroon, Central Africa. Int J Cancer 1999;81:189-92., 822Bourboulia D, Whitby D, Boshoff C, et al. Serologic evidence for mother-to-child transmission of Kaposi sarcoma-associated herpesvirus infection. JAMA 1998;280:31-2., 823Whitby D, Smith NA, Matthews S, et al. Human herpesvirus 8: seroepidemiology among women and detection in the genital tract of seropositive women. J Infect Dis 1999;179:234-6., 824Plancoulaine S, Abel L, van Beveren M, et al. Human herpesvirus 8 transmission from mother to child and between siblings in an endemic population. Lancet 2000;356:1062-5.).