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Human herpesvirus 8 (HHV-8) is a transmissible DNA virus, with similarities in DNA structure to Epstein-Barr virus. HHV-8 has been causally linked to all forms of KS (HIV-related and endemic KS) and with two rare neoplastic conditions usually associated with HIV infection, body cavity-based lymphoma and multicentric Castleman disease. The exact mechanism by which HHV-8 infection leads to neoplastic disease has not been fully elucidated, but seroconversion to HHV-8 antibody positivity virtually always precedes development of the tumors (789Gao 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.). Higher plasma HHV-8 DNA titers are associated with increased risk for KS (790Lennette 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.).

The prevalence of antibodies to HHV-8 varies widely with age and geography. In the United States and Europe, 1%-3% of the general adult population is seropositive, with higher rates (8%) among men who have sex with men (791Engels EA, Atkinson JO, Graubard BI, et al. Risk factors for human herpesvirus 8 infection among adults in the United States and evidence for sexual transmission. J Infect Dis 2007;196:199-207.). Among other adult men in the general population, HHV-8-seropositivity was marginally associated with duration of heterosexual activity and positively associated with the number of lifetime sex partners and coinfection with HBV and HSV type 2 viruses; none of these were significantly associated with risk for women. In contrast, the seropositivity rate in some areas of Africa is >80% (792Whitby 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., 793Goedert JJ, Kedes DH, Ganem D. Antibodies to human herpesvirus 8 in women and infants born in Haiti and the USA. Lancet 1997;349:1368., 794Huang 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., 795Serraino 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.).

HHV-8 is transmitted through oral and genital secretions. Immunocompetent HHV-8-infected adults frequently shed HHV-8 in their oropharyngeal secretions, with virus detected in saliva on 22% of test days (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.). In areas where HHV-8 infection is endemic, the seroprevalence increases quickly during the first 5 years of life, especially when other family members are HHV-8-positive, then plateaus until adolescence and young adult years. In a study in rural Tanzania, the rate of positivity for HHV-8 was 3.7% among infants, 58% among children aged 4-5 years, and 89% among adults aged >45 years (797Mbulaiteye SM, Pfeiffer RM, Whitby D, et al. Human herpesvirus 8 infection within families in rural Tanzania. J Infect Dis 2003;187: 1780-5.). The incidence among infants and children increased with the number of HHV-8-positive parents and siblings in the home, indicating nonsexual transmission for prepubertal children, with a limited role for perinatal transmission (797Mbulaiteye SM, Pfeiffer RM, Whitby D, et al. Human herpesvirus 8 infection within families in rural Tanzania. J Infect Dis 2003;187: 1780-5., 798He J, Bhat G, Kankasa C, et al. Seroprevalence of human herpesvirus 8 among Zambian women of childbearing age without Kaposi's sarcoma (KS) and mother-child pairs with KS. J Infect Dis 1998;178: 1787-90., 799Gessain 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., 800Sitas F, Newton R, Boshoff C. Increasing probability of mother-tochild transmission of HHV-8 with increasing maternal antibody titer for HHV-8. N Engl J Med 1999;340:1923., 801Calabro ML, Gasperini P, Barbierato M, et al. A search for human herpesvirus 8 (HHV-8) in HIV-1 infected mothers and their infants does not suggest vertical transmission of HHV-8. Int J Cancer 2000; 85:296-7., 802Plancoulaine 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., 803Malope BI, Pfeiffer RM, Mbisa G, et al. Transmission of Kaposi sarcomaassociated herpesvirus between mothers and children in a South African population. J Acquir Immune Defic Syndr 2007;44:351-5.).

In the United States, among a cohort of high-risk HIV-infected and HIV-negative adolescents, with a median age of 19 years, 11.2% were HHV-8-positive (804Casper C, Meier AS, Wald A, et al. Human herpesvirus 8 infection among adolescents in the REACH cohort. Arch Pediatr Adolesc Med 2006;160:937-42.). The highest rates were in adolescent HIV-infected males reporting sex with males (23%). Seropositivity was associated with HIV infection, men who have sex with men, a history of syphilis, and injection-drug use (804Casper C, Meier AS, Wald A, et al. Human herpesvirus 8 infection among adolescents in the REACH cohort. Arch Pediatr Adolesc Med 2006;160:937-42., 805Cannon MJ, Dollard SC, Smith DK, et al. Blood-borne and sexual transmission of human herpesvirus 8 in women with or at risk for human immunodeficiency virus infection. N Engl J Med 2001;344:637-43.).

HHV-8 also may be transmitted through exposure to infected blood. Adult injection-drug users have an increased rate of HHV-8 positivity (804Casper C, Meier AS, Wald A, et al. Human herpesvirus 8 infection among adolescents in the REACH cohort. Arch Pediatr Adolesc Med 2006;160:937-42., 805Cannon MJ, Dollard SC, Smith DK, et al. Blood-borne and sexual transmission of human herpesvirus 8 in women with or at risk for human immunodeficiency virus infection. N Engl J Med 2001;344:637-43.). In addition, recent evidence suggests that HHV-8 may be transmitted through blood product transfusions. In one study in an area of Uganda with a high incidence of HHV-8-seropositivity, the excess risk for acquiring HHV-8 through transfusion was nearly 3%, recipients of HHV-8 antibody-positive blood were compared with those receiving HHV-8-negative blood (806Hladik W, Dollard SC, Mermin J, et al. Transmission of human herpesvirus 8 by blood transfusion. N Engl J Med 2006;355:1331-8.).

A small study suggested that maternal HHV-8 infection might increase risk for perinatal transmission of HIV, although no evidence of HHV-8 infection was identified among HIV-infected infants (801Calabro ML, Gasperini P, Barbierato M, et al. A search for human herpesvirus 8 (HHV-8) in HIV-1 infected mothers and their infants does not suggest vertical transmission of HHV-8. Int J Cancer 2000; 85:296-7.). Women coinfected with HHV-8 and HIV had increases in both HHV-8 and HIV viral load in serum and/or cervical fluid during pregnancy (807Lisco 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.).

During the pre-HAART era, the overall incidence of KS among HIV-infected adults was as high as 20%. However, the rate among children was low. In the United States and England, KS represented <1% of pediatric AIDS-defining illnesses.

The incidence of KS appeared to decline even before the widespread use of HAART. The reason for this decline was unclear but may have been related to the use of other antiviral agents, such as those used to treat CMV (i.e., foscarnet, ganciclovir, and cidofovir), which may inhibit HHV-8 (808Glesby 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., 809Mocroft A, Youle M, Gazzard B, et al. Anti-herpesvirus treatment and risk of Kaposi's sarcoma in HIV infection. Royal Free/Chelsea and Westminster Hospitals Collaborative Group. AIDS 1996;10:1101-5., 810Cannon JS, Hamzeh F, Moore S, et al. Human herpesvirus 8-encoded thymidine kinase and phosphotransferase homologues confer sensitivity to ganciclovir. J Virol 1999;73:4786-93., 811Neyts J, De Clercq E. Antiviral drug susceptibility of human herpesvirus 8. Antimicrob Agents Chemother 1997;41:2754-6., 812Kedes DH, Ganem D. Sensitivity of Kaposi's sarcoma-associated herpesvirus replication to antiviral drugs. Implications for potential therapy. J Clin Invest 1997;99:2082-6., 813Robles R, Lugo D, Gee L, et al. Effect of antiviral drugs used to treat cytomegalovirus end-organ disease on subsequent course of previously diagnosed Kaposi's sarcoma in patients with AIDS. J Acquir Immune Defic Syndr Hum Retrovirol 1999;20:34-8., 814Cannon MJ, Laney AS, Pellett PE. Human herpesvirus 8: current issues. Clin Infect Dis 2003;37:82-7.). KS, primary effusion lymphoma, and multicentric Castleman disease are described most frequently among HIV-infected persons with more advanced immunosuppression (CD4 count of <200 cells/mm³), but they can occur at any CD4 count. With the advent of earlier and more aggressive HAART, the incidence of KS in adults has continued to decrease (815Ledergerber B, Egger M, Erard V, et al. AIDS-related opportunistic illnesses occurring after initiation of potent antiretroviral therapy: the Swiss HIV Cohort Study. JAMA 1999;282:2220-6.).

Although KS occurs primarily in adults, the incidence in children has increased substantially as a result of the HIV pandemic, particularly in Africa, and the frequent use of immunosuppressive drugs. One series reported a 40-fold increase in incidence of childhood KS in Uganda in the era of AIDS (816Ziegler JL, Katongole-Mbidde E. Kaposi's sarcoma in childhood: an analysis of 100 cases from Uganda and relationship to HIV infection. Int J Cancer 1996;65:200-3.).

A febrile illness with mild respiratory symptoms and a maculopapular rash has been associated with primary infection in young immunocompetent children (817Andreoni M, Sarmati L, Nicastri E, et al. Primary human herpesvirus 8 infection in immunocompetent children. JAMA 2002;287:1295-300.). A similar self-limited illness has been described in adults with primary infection. Evidence suggests more significant symptomatology among immunodeficient adults with primary infection, including reports of fever, arthralgia, splenomegaly, and bone marrow suppression (818Luppi M, P. B, TF. S, et al. Bone marrow failure associated with human herpesvirus 8 infection after transplantation. N Engl J Med 2000;343:1378-85., 819Luppi M, Barozzi P, Rasini V, et al. Severe pancytopenia and hemophagocytosis after HHV-8 primary infection in a renal transplant patient successfully treated with foscarnet. Transplantation 2002;74:131-2.).

KS presentation varies widely, but most persons have nontender, purplish, indurated skin lesions; intraoral lesions can be seen and visceral dissemination can occur, occasionally without skin lesions. Multicentric Castleman disease presents with generalized adenopathy and fever and may progress to multiorgan failure.

The laboratory diagnosis of HHV-8 is most commonly based on serologic assays, such as immunofluorescence, enzymelinked immunosorbent assay, and Western blot. However, without a standard for diagnosing HHV-8 infection, these tests range in sensitivity from 80% to ≥90% and demonstrate poor interassay agreement (820Bhaduri-McIntosh S. Human herpesvirus-8: clinical features of an emerging viral pathogen. Pediatr Infect Dis J 2005;24:81-2.). Combination assays containing both lytic and late-phase antigens may improve detection rates. Nucleic acid-based tests, such as in situ DNA hybridization and PCR, are important for pathologic diagnoses in biologic specimens. Although these tests have high levels of sensitivity, specificity and reproducibility are highly variable. Routine screening for HHV-8 by PCR or serologic testing is not indicated for HIV-infected persons.

Rapid progression of KS after initiation of HAART and after a change from a failing regimen to a more potent one have been reported. Progression of KS, representing IRIS, usually appeared within 8 weeks after start of a potent HAART regimen. Most patients experienced rapid progression of cutaneous lesions; however, sudden worsening of pulmonary KS, with resultant deaths, was reported in at least four patients. All reported fatalities were linked to pulmonary KS. In most cases, HAART was continued with stabilization and then regression of lesions. In more severe cases, especially those involving visceral lesions, chemotherapy was instituted and, in combination with HAART, led to regression of the KS (827Leidner RS, Aboulafia DM. Recrudescent Kaposi's sarcoma after initiation of HAART: a manifestation of immune reconstitution syndrome. AIDS Patient Care STDS 2005;19:635-44., 828Bower M, Nelson M, Young AM, et al. Immune reconstitution inflammatory syndrome associated with Kaposi's sarcoma. J clin Oncol 2005;23:5224-8.).

No recommendations exist for management of treatment failure.

Effective suppression of HIV replication with HAART 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).

Not applicable.