Frequency of HHV8 detection in peripheral blood cells in patients with Kaposi's sarcoma.

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Background: HHV8 is found in virtually all Kaposi's sarcoma (KS) lesions but only some KS patients have detectable human herpesvirus 8 (KSHV, HHV8) DNA in peripheral blood. Methods: To determine the frequency with which HHV8 could be detected in the peripheral blood of patients prior to the diagnosis of KS, serial archived blood samples were analyzed by nested PCR. The clinical course of the patients was obtained from the Swiss HIV Cohort Study group database and chart abstraction. Results: Nine of twenty patients from the Swiss HIV Cohort study (SHCS) had detectable HHV8 DNA prior to the development of KS; 3/16 patients after KS diagnosis. HHV8 was detected 6-26 months before the clinical presentation of K.S. Very low CD4 counts were not associated with an increased rate of HHV8 DNA detection. Three of these nine patients only had HHV8 detected when triple sample volume was used for the nested PCR assays. The other six patients had readily detectable HHV8 DNA. There was no significant difference in the age of the patients at diagnosis, or time since diagnosis of HIV seropositivity in patients with and without detectable HHV8. The minimum follow-up for the surviving patients was 20 months after the diagnosis of KS. The two patients with persistently detectable KSHV DNA in their PBMCs died within 12 months of KS diagnosis. Patient#2 had progressive KS at the time of death and patient #12 died with probable pulmonary KS and a cardiomyopathy. The survival is better in the group without detectable HHV8 DNA which has a markedly depressed median CD4 count(median = 0.020), compared to the patients with readily detectable HHV8 DNA(median = 0.180). We have analyzed blood samples from four additional patients undergoing therapy for KS at UNC. The one patient, with 3/3 HHV8 DNA positive blood samples, died with progressive cutanous KS and wasting 1 month after the last sample was collected. Three other patients have responded to therapy and have only intermittently positive blood samples. Conclusions: 3/3 patients with persistent high level HHV8 DNA, 2/7 patients with intermittent high level HHV8 DNA but only 1/14 patients with low or undetectable HHV8 DNA died with progressive KS. We propose that I) high level viremia occurs 1 to 2 years prior to KS and 2) persistent high level viremia is not required for KS development but may be associated with a poor prognosis.