The Prevalence of HIV-1 DNA in AIDS-Related Lymphoma throughout the Epidemic in the US

Abstract 5205

Kaposi sarcoma (KS) and non-Hodgkin lymphoma (NHL) are the two most common AIDS-defining cancers and significantly contribute to HIV-related deaths. While highly active antiretroviral therapy (HAART) has produce a sharp decline in the incidence of KS and AIDS-related NHL (ARL), HIV-infected patients are still at a high risk for developing these malignancies. Recent studies evaluating HIV-1 DNA in 91 AIDS-related KS cases demonstrated a significant decrease in the prevalence of HIV-1 DNA positive KS cases post-HAART (after 1996; 16.7%) as compared to pre-HAART (before 1996; 45%) corresponding to the decrease in incidence of this cancer since the introduction of HAART. Additionally HIV was more prevalent in sites of visceral KS (51.9%) as compared to skin KS (30.7%). We have recently evaluated the HIV sequence evolution in the context of metastatic ARL and identified lymphoma-specific HIV compartmentalized within tumor sites that was genetically distinct from HIV in non-tumor sites suggesting a specific form of HIV arises within individuals who develop ARL. The goal of this research was to determine the prevalence and quantity of HIV DNA in 119 ARL biopsies representing the entire span of the HIV epidemic (1982–2005). Whole genomic amplification was performed on DNA extracted from three 10um paraffin embedded tissue sections and the presence of HIV-1 DNA was determined by quantitative amplification of the HIV gag gene. Of the 119 cases, 45% contained detectable levels of HIV DNA. The HIV antigen was predominantly localized to macrophages. A subset of the ARL cases in this study contained approximately 1 HIV copy per cell which is extremely high considering previously reported data describing HIV-infected lymph nodes contained approximately 1 HIV copy per 1000 cells. Similar to what was observed for KS, the prevalence of HIV-positive ARLs has decreased in the post-HAART era (39%) when compared to pre-HAART (54%). While the prevalence of HIV-1 DNA positive ARLs declined in the post-HAART era, it was not to the same extent as what was observed for KS. Thus, our data is consistent with a decrease in the incidence of both tumor types in the post-HAART era. The higher prevalence of HIV-1 DNA in visceral sites of KS and lymphoma specific-HIV sequences in sites of metastatic lymphoma suggests that HIV, especially HIV infected macrophages, may play a role in the pathogenesis of KS and ARL disease progression.