Trends in Kaposi's sarcoma-associated Herpesvirus antibodies prior to the development of HIV-associated Kaposi's sarcoma: A nested case-control study

HIV-associated Kaposi's sarcoma (KS) is a public health challenge in sub-Saharan Africa since both the causative agent, Kaposi's sarcoma associated-herpesvirus (KSHV), and the major risk factor, HIV, are prevalent. In a nested case-control study within a long-standing clinical cohort in rural Uganda, we used stored sera to examine the evolution of antibody titres against the KSHV antigens K8.1 and latency-associated nuclear antigen (LANA) among 30 HIV-infected subjects who subsequently developed HIV-related KS (cases) and among 108 matched HIV/KSHV coinfected controls who did not develop KS. Throughout the 6 years prior to diagnosis, antibody titres to K8.1 and LANA were significantly higher among cases than controls (p<0.0001), and titres increased prior to diagnosis in the cases. K8.1 titres differed more between KS cases and controls, compared to LANA titres. These differences in titre between cases and controls suggest a role for lytic viral replication in the pathogenesis of HIV-related KS in this setting. What's New? Infection with Kaposi sarcoma associated-herpesvirus (KSHV) and HIV, the major risk factor for Kaposi sarcoma, is common in sub-Saharan Africa. However, little is known about the evolution of KSHV antibody responses in HIV-infected individuals prior to the clinical onset of KS. This study shows that antibody titres against KSHV antigens K8.1 and latency-associated nuclear antigen (LANA) increase significantly in the six years leading up to HIV-associated KS. Titres of K8.1, a lytic antigen, rose more than LANA titres, indicating that the activation of genes in the lytic cycle of viral replication is important in KS development.