Human Herpesvirus 8 Disease

Abstract

EpidemiologyHuman 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 Kaposi sarcoma (KS) (HIV-related and endemic) and with two rare neoplastic conditions usually associated with HIV infection: body cavity-based lymphoma, also known as primary effusion lymphoma (a B-cell lymphoma that typically arises in body cavities such as the pleural space) and multicentric Castleman disease (non-cancerous tumors that may develop in lymph nodes in a single site or in multiple sites throughout the body). 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. 1 Higher plasma HHV-8 DNA titers are associated with increased risk of KS. 2 The prevalence of antibodies to HHV-8 varies widely with age and geography. In the United States and Europe, 1% to 3% of the general adult population is seropositive, with higher rates (8%) among men who have sex with men (MSM). 3 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 co-infection with hepatitis B virus and herpes simplex virus type 2 viruses; none of these were significantly associated with risk for women. In contrast, the adult seropositivity rate in Mediterranean countries ranges from 10 to 25%. In areas where HHV-8 is endemic, such as eastern and central Sub-Saharan Africa, HHV-8 seropositivity rates as high as 80% have been reported in adults. [4][5][6][7][8] HHV-8 is transmitted through oral and genital secretions. Immunocompetent HHV-8-infected adults frequently shed HHV-8 in their oropharyngeal secretions, with viral DNA detected in saliva on 22% of test days. 9 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 studies from rural Tanzania and Uganda, the rate of positivity for HHV-8 was 3.7% Panel's Recommendations• Effective suppression of HIV replication with combination antiretroviral therapy (cART) is recommended to reduce the risk of human herpesvirus 8-(HHV-8)-associated Kaposi sarcoma (AIII).• Routine testing to identify HHV-8-seropositive, HIV-infected patients is not recommended (BIII).• Effective suppression of HIV replication with cART is recommended for all patients with evidence of active KS and other human herpesvirus 8-associated malignant lymphoproliferative disorders (AIII).• The use of intravenous ganciclovir or oral valganciclovir is recommended for treatment of HHV-8-associated multicentric Castleman disease (BIII) and may be a useful adjunct for treating HHV-8-associated primary effusion lymphoma (BIII).• Appropriate chemotherapy, in combination with potent cART, should be ...