KSHV/HHV-8 and Kaposi's Sarcoma

Kaposi’s sarcoma-associated herpesvirus (KSHV), also known as human herpesvirus 8 (HHV-8), is the first gamma-2 member of the herpesvirus family known to infect humans. KSHV is now firmly established as the causal agent of Kaposi’s sarcoma (KS), although its role in other conditions is more controversial. The epidemiology of KSHV has proven to be complex. In the Americas and Northern Europe, KSHV is common among homosexual men but otherwise rare in the general population. KSHV is rare in the rest of the world with the exception of Southern Europe, the Middle East, and Africa. Even within Africa, there are at least two epidemiologic patterns of KSHV transmission. The exact mechanisms of KSHV transmission are not understood, but saliva is clearly the conduit most responsible for spread and several heretofore underappreciated practices which pass saliva from person to person may be operative in KSHV transmission. KS, the primary end-organ manifestation of KSHV, still remains an important source of morbidity and mortality worldwide. In Africa, KS is the most common malignancy in most parts of the populous sub-Saharan region. Despite the growing availability of antiretroviral therapy (ART) in Africa, lack of chemotherapy results in mortality continuing to be high for patients who develop KS. Furthermore, recent data have documented a high incidence of KS-related immune reconstitution inflammatory syndrome (IRIS) among patients receiving ART. Finally, in the U.S., a number of cases of KS have developed in HIV-infected adults who were otherwise effectively being treated with ART as evidenced by undetectable plasma HIV RNA levels and elevated CD4+ T cell counts. These cases, which clinically resemble the relatively indolent variant known as “classic KS”, have led to the speculation that immunosenescence in the HIV-infected host could lead to a second wave of KS as the HIV-infected population ages.