Relationship of KSHV/HHV-8 Replication to Extent and Course of Kaposi's Sarcoma and Response to Therapy.

Abstract

26 Objectives: To determine if KSHV/HHV-8 burden correlates with extent or progression of Kaposi's sarcoma (KS) and can predict or reflect treatment response. Methods: DNA QC PCR capable of detecting HHV-8 at the single copy level and quantitating 5 copies of HHV-8 per 106 PBMC was used to determine viral burden. KSHV message levels in PBMC samples were determined by RT PCR, using L32 ribosomal protein RNA as an internal control. Samples analyzed included PBMC: [1] a historical cross-section of KS patients, [2] PBMC from a KS/ AZT trial, [3] KS lesions treated with topical 9-cis retinoic acid (RA), and [4] PBMC from KS patients on triple-drug antiretroviral therapy. Results: KSHV/HHV-8 burden was found not to be unrelated to CD4 count, or HIV-1 plasma RNA, overall, though trends for falling HIV and HHV-8 burden were seen in patients treated with triple-drug therapy. HHV-8 burden was higher in patients with CMV, HSV, and VZV infections. Patients treated with ganciclovir or foscavir did not have lower average PBMC HHV-8 burdens. Patients without mucosal or visceral disease were found to have low to undetectable (≤5-5×102 copies/106 PBMC) PBMC burden while patients with mucosal disease or visceral disease displayed significantly higher PBMC burden (2×103-104 copies/106 PBMC). High or increasing HHV-8 burden was associated with progression of Kaposi's sarcoma. Cytotoxic chemotherapy (or αINF) and topical RA treatment reduced viral burden by an average of 80% in blood or lesions respectively. Results of message expression will be discussed. Conclusions: HHV-8 PBMC does not reflect Immunodeficiency or activity of HIV disease. HHV-8 QC PCR may show promise as a tool for both prediction of risk of progression and assessment of response in KS patients.