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

Abstract

Kaposi's sarcoma-associated herpesvirus (KSHV) DNA, consistently found in Kaposi's sarcoma (KS) tissues, was sought in peripheral blood mononuclear cells (PBMCs) of HIV-infected individuals. To determine quantitative relationships between the presence of KSHV DNA in PBMCs, CD4 cell counts, plasma HIV RNA levels, and the development of KS, we designed a cross-sectional study of prospectively collected PBMC samples from ongoing cohort studies. PBMCs were collected from 142 HIV-seropositive individuals in California, 7 of whom had a clinical diagnosis of KS. KSHV sequences were detected in extracted PBMC DNA by nested polymerase chain amplification using two nonoverlapping primer sets. KSHV DNA was detected in PBMCs of 5 of 7 (71%) subjects with KS and in 18 of 135 (13%) HIV-infected subjects without KS. Among HIV-seropositive individuals without KS, detection of KSHV was more common in men 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/microl, p = 0.05), and higher geometric mean plasma HIV RNA (4.83 versus 4.03 1og10 copies/ml, p = 0.0002). Semiquantitative 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 development of KS in subjects with higher KSHV loads. The association of the presence of KSHV DNA in PBMCs with lower CD4 cell counts and higher plasma HIV RNA provides evidence of a relationship between immunosuppression, HIV replication, and KSHV expression.

Viral Load of Human Herpesvirus 8 in Peripheral Blood of Human Immunodeficiency Virus-Infected Patients with Kaposi's Sarcoma

“…We evaluated both cell-free and cell-associated HHV-8 DNA in sequential clinical samples from KS patients and found satisfactory reproducibility. We also found that HHV-8 viral loads have an association with HIV viral load in KS HIV-infected patients, suggesting a synergistic interaction between HHV-8 and HIV, as also reported in another study (29). However, HHV-8 viral loads are variable and fluctuate over time.…”

Spectrum of Kaposi's Sarcoma-Associated Herpesvirus, or Human Herpesvirus 8, Diseases

“…Ariyoshi et al (13) also found that in Gambia, West Africa, KS is less frequent in HIV-2-positive individuals in spite of evidence of HHV-8 infection. In HIV patients with no diagnosis of KS, HHV-8 DNA has been found in 13% (18 of 135) of the PBMCs of the patients studied (198). Furthermore, HHV-8 DNA in PBMCs and lower CD4 ϩ cell counts correlated with elevated plasma levels of HIV mRNA, giving good evidence for the relationship between immunosuppression, HIV replication, and HHV-8 expression (84,198).…”

Multiple viral coinfections among HIV/AIDS patients in China

“…Due to the unavailability of blood-based, type-specific commercial products for testing, we did not test for human papillomavirus (HPV) which is also prevalent in China and is the causal agent of invasive cervical cancer, an important AIDS-defining disease. Also, due to lack of qualified commercial products for testing, we did not test for human herpes virus type 8 (HHV8) which was first identified in 1994 and has been demonstrated to be prevalent in the Mediterranean region and the causal agent of Kaposi's Sarcoma (KS), another important AIDS-defining disease (33)(34)(35)(36). This limited our ability to draw conclusions with regard to the spectrum of viral coinfections that are of most significance to Chinese HIV/AIDS patients.…”