Kaposi's sarcoma-associated herpesvirus (KSHV) is the viral etiologic agent of Kaposi's sarcoma (KS). In sub-Saharan Africa, the catastrophic intersection between underlying endemic infection with KSHV and the HIV epidemic has resulted in KS becoming the most common malignancy among adults in many countries and a growing cause of cancer in children. In areas where KS is most common in Africa ("the KS belt" in equatorial East and Central Africa), KSHV is primarily acquired in childhood, but little is known about biological determinants of KSHV infection in children or manifestations of primary infection. Data are especially limited regarding whether HIV influences susceptibility to KSHV infection or modifies the initial disease course. The proposed research will examine interactions between HIV and KSHV in Ugandan children by conducting one of the first longitudinal examinations of KSHV infection in African children. Our specific aims are to (1) compare KSHV prevalence between HIV-infected and HIV-uninfected children; (2) ascertain the role of HIV infection in acquiring new KSHV infection among African children; and (3) determine clinical and laboratory manifestations of primary KSHV infection in African children and determine whether HIV infection modifies these manifestations. To achieve these aims, we will employ a cost-efficient approach of using existing biological samples and data collected in two previously assembled cohorts of HIV-infected and -uninfected Ugandan children. This study will provide the requisite data for an NIH R01 proposal to support the dedicated investigation of the behavioral and environmental determinants of KSHV infection in childhood in sub-Saharan Africa.