Detection of Kaposi's sarcoma-associated herpesvirus in peripheral blood cells in human immunodeficiency virus infection: Association with Kaposi's sarcoma, CD4 cell count, and HIV RNA levels

Kaposi's sarcoma-associated herpesvirus (KSHV) DNA, consistently found in K aposi's sarcoma (KS) tissues, was sought in peripheral blood mononuclear ce lls (PBMCs) of HIV-infected individuals. To determine quantitative relation ships between the presence of KSHV DNA in PBMCs, CD4 cell counts, plasma HI V RNA levels, and the development of KS, we designed a cross-sectional stud y of prospectively collected PBMC samples from ongoing cohort studies. PBMC s were collected from 142 HIV-seropositive individuals in California, 7 of whom had a clinical diagnosis of KS. KSHV sequences were detected in extrac ted PBMC DNA by nested polymerase chain amplification using two nonoverlapp ing primer sets. KSHV DNA was detected in PBMCs of 5 of 7 (71%) subjects wi th KS and in 18 of 135 (13 %) HIV-infected subjects without KS. Among HIV-s eropositive individuals without KS, detection of KSHV was more common in me n than women (19 versus 4%,p = 0.01) and was associated with lower mean CD4 percent (14.8 versus 20.7% CD4 cells, p = 0.03), lower mean CD4 cell count (244 versus 334 CD4 cells/mu l, p = 0.05), and higher geometric mean plasm a HIV RNA (4.83 versus 4.03 log(10) copies/ml, p = 0.0002). Semiquantitativ e analysis found 5 to 15,625 copies of KSHV per microgram of PBMC DNA with increased plasma HIV RNA levels and a trend toward increased subsequent dev elopment of KS in subjects with higher KSHV loads. The association of the p resence of KSHV DNA in PBMCs with lower CD4 cell counts and higher plasma H IV RNA provides evidence of a relationship between immunosuppression, HIV r eplication, and KSHV expression.