Effects of Chemotherapy in AIDS-Associated Non-Hodgkin's Lymphoma on Kaposi's Sarcoma Herpesvirus DNA in Blood

Abstract

A B S T R A C T PurposeTo determine the relative frequency with which Kaposi's sarcoma-associated herpesvirus/HHV-8 (KSHV) DNA is detected in peripheral-blood mononuclear cells (PBMCs) and in plasma of patients with AIDS-KS and AIDS-associated non-Hodgkin's lymphoma (NHL; AIDS-NHL); to determine whether the presence of viral DNA in plasma reflects lysis of tumor cells or reflects the presence of viremia (ie, virion-encapsidated DNA); and to determine the effect of lymphoma therapy on KSHV DNA. Patients and MethodsSamples were obtained from patients enrolled in AIDS Malignancy Consortium clinical trials and from healthy donors. Real time PCR was used to quantify KSHV DNA in peripheral blood mononuclear cells (PBMC) and plasma. DNase digestion and fragment size determination studies were used to characterize the DNA detected.

Assessment of immunovirological features in HIV related non-Hodgkin lymphoma patients and their impact on outcome

“…27 When compared to previous studies, lower HHV8 infection prevalence (7.4%) and no virus reactivation emerged in our patients without a history of virus-related disease. In a nested case control study, 28 14% of NHL HIV patients were HHV8 DNA positive and Lin et al 10 detected HHV8 DNA in both PBMCs (19%) and plasma (22%) declining with chemotherapy. Since the spectrum of HHV8-associated lymphomas is in expansion and the virus quite prevalent among HIV+, viremia evaluation could be an auxiliary biomarker to consider in this context, as suggested.…”

“…Since the spectrum of HHV8-associated lymphomas is in expansion and the virus quite prevalent among HIV+, viremia evaluation could be an auxiliary biomarker to consider in this context, as suggested. 10 Our study carries several weaknesses, such as the retrospective nature of the investigation, the small number of patients, and the short longitudinal time of follow-up, without a timeline to describe the kinetic of EBV DNA and immunological changes, as related to disease evolution. In order to contribute further clues in understanding the pathogenic mechanisms of HIV related NHL, the study impact should be validated in a larger number of patients with welldefined timing.…”

“…9 Recently, a broader relationship between HHV8 infection and ARL has been proposed, beyond that one known for clinically distinctive primary effusion lymphoma. 10 HIV contribution to lymphomagenesis as pro-virus was also suggested, through deregulation of oncogenes expression and/or transcription factors. 11 Despite the HAART control on virus replication, HIV persists at low levels mainly in infected, resting CD4+ T cells, the stable viral reservoir.…”

Brief Report

“…KSHV DNA was quantified in plasma at baseline, cycles 2 and 5, and treatment discontinuation, using competitive DNA PCR [31]. Whole blood CD4+ T cell counts and plasma HIV RNA levels were determined at these same time points.…”

Human herpesvirus 8-associated neoplasms

“…HHV-8 DNA is detected more frequently and at higher copy numbers in plasma of KS patients compared to controls with asymptomatic HHV-8 infection [19,20,21*,22*]. A large proportion of this HHV-8 DNA in plasma is encapsidated in virions [21*,23], indicating an association between KS and systemic viral replication and dissemination.…”