Human herpesvirus 8 load and progression of AIDS-related Kaposi sarcoma lesions (original) (raw)
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Relationship of human herpesvirus 8 peripheral blood virus load and Kaposi's sarcoma clinical stage
AIDS, 2000
To determine the relationship between human herpesvirus 8 (HHV-8 or Kaposi's sarcoma-associated herpesvirus) peripheral blood virus load and Kaposi's sarcoma (KS) clinical stage. Design: Blinded, cross-sectional analysis of peripheral blood HHV-8 DNA levels in persons with AIDS-related KS in Harare, Zimbabwe. Methods: Subjects were strati®ed by KS clinical stage. The amount of HHV-8 DNA in plasma and peripheral blood mononuclear cells (PBMC) was determined by quantitative real-time PCR ampli®cation of the HHV-8 open reading frame 26. Results: Thirty-one HIV-1/HHV-8-coinfected persons were studied: 26 subjects had histologically con®rmed KS (one stage II, 11 stage III and 14 stage IV) and ®ve subjects had antibodies to HHV-8 but did not have KS. The age, CD4 lymphocyte count and plasma HIV-1 RNA levels were similar in all groups. HHV-8 DNA was detected in the plasma of all HHV-8-infected subjects (range , 2.4 to 5.2 log 10 copies/ml), but plasma HHV-8 DNA levels were not associated with KS disease stage. In contrast, the amount of HHV-8 DNA in PBMC (range , 0.7 to 4.5 log 10 copies/ìg) was strongly associated with KS clinical stage (P 0.005). Among stage IV KS cases, there was a linear relationship between plasma and PBMC HHV-8 DNA levels (r 2 0.42; P 0.01). Conclusion: The strong association observed between the extent of KS disease and the levels of HHV-8 DNA in PBMC provides further evidence for a relationship between HHV-8 virus load and KS pathogenesis.
HHV-8 infection in patients with AIDS-related Kaposi's sarcoma in Brazil
Brazilian Journal of Medical and Biological Research, 2001
The aims of the present study were to determine the prevalence of human herpesvirus type 8 (HHV-8) in HIV-positive Brazilian patients with (HIV+/KS+) and without Kaposis sarcoma (HIV+/KS-) using PCR and immunofluorescence assays, to assess its association with KS disease, to evaluate the performance of these tests in detecting HHV-8 infection, and to investigate the association between anti-HHV-8 antibody titers, CD4 counts and staging of KS disease. Blood samples from 66 patients, 39 HIV+/KS+ and 27 HIV+/KS-, were analyzed for HHV-8 viremia in peripheral blood mononuclear cells by PCR and HHV-8 antigenemia for latent and lytic infection by immunofluorescence assay. Positive samples for latent nuclear HHV-8 antigen (LNA) antibodies were titrated out from 1/100 to 1/409,600 dilution. Clinical information was collected from medical records and risk behavior was assessed through an interview. HHV-8 DNA sequences were detected by PCR in 74.3% of KS+ patients and in 3.7% of KS-patients. Serological assays were similar in detecting anti-LNA antibodies and anti-lytic antigens in sera from KS+ patients (79.5%) and KS-patients (18.5%). HHV-8 was associated with KS whatever the method used, i.e., PCR (odds ratio (OR) = 7.4, 95% confidence interval (CI) = 2.16-25.61) or anti-LNA and anti-lytic antibodies (OR = 17.0, 95%CI = 4.91-59.14). Among KS+ patients, HHV-8 titration levels correlated positively with CD4 counts (rho 0.48, P = 0.02), but not with KS staging. HHV-8 is involved in the development of KS in different geographic areas worldwide, as it is in Brazil, where HHV-8 is more frequent among HIV+ patients. KS severity was associated with immunodeficiency, but no correlation was found between HHV-8 antibody titers and KS staging.
Journal of Clinical Microbiology, 2005
Africa. In a series of 36 AIDS-KS cases from Central African Republic, we showed, using a real-time PCR quantitative assay, the high frequency (82%) of detectable HHV-8 DNA in peripheral blood mononuclear cells (PBMCs). We also found that the level of antibodies directed against lytic or latent HHV-8 antigens is not correlated to the amount of HHV-8 viral load in the PBMCs, and finally, we demonstrated a much higher viral load in tumoral skin lesions (6.07 log copies/g DNA) than in unaffected skin (2.93 log copies/g DNA) or in PBMCs (2.55 log copies/g DNA).
Infectious Agents and Cancer, 2008
The association of the human herpesvirus-8/Kaposi's sarcoma (KS)-associated herpesvirus (HHV-8/KSHV) serology with various malignancies in Tanzania is not currently well established while previous studies were based on either PCR or immunofluorescence assays [IFA] but not with a sensitive enzyme-linked immunosorbent assay (ELISA). Selected archival diagnostic biopsies (n = 184) and sera from indigenous patients with KS (n = 120), non-KS tumors (n = 24) and non-neoplastic lesions (n = 40) at Muhimbili National Hospital (MNH), Tanzania, were evaluated by diagnostic histopathology, immunohistology [anti-HHV-8 latency-associated nuclear antigen (LANA)] and serology for HIV (ELISA) and HHV-8 (IFA and ELISA).
Journal of Medical Virology, 2009
Differences in the prevalence of human herpesvirus 8 (HHV-8) and Kaposi's sarcoma (KS) have been described, depending on the study population and their geographic origin. A cross- sectional study aimed at detecting the frequency and titers of antibodies against HHV-8 latent and lytic antigens in serum samples from individuals with different risk-factors for HHV-8 infection, as well as predictive marker identification in patients with KS, was conducted. Serum samples were collected from seven groups of individuals: 75 patients with AIDS-KS, 5 with classic KS, 16 with African KS, 495 with HIV/AIDS, 805 patients with chronic kidney disease, 683 handicapped individuals, and 757 health care workers. Samples were evaluated for the presence and titers of HHV-8-specific antibodies to latent and lytic antigens using "in house" immunofluorescence assays. The results were analyzed by the Chi-square, Fisher's exact test, Kruskal-Wallis and/or Mann-Whitney U-tests. The frequencies of HHV-8 antibodies were as follows: 87.5-100% in patients with KS, 20.4% in patients with HIV/AIDS, 18% in patients with chronic kidney disease, 1.6% in handicapped individuals, and 1.1% in health care workers. A greater number of samples were antibody positive to lytic antigens. Elevated titers of antibodies to latent and lytic antigens, mostly among patients with KS, were detected. Using established serological assays, different "at-risk" populations for HHV-8 infection/disease were detected in this geographic area, confirming HIV/AIDS and identifying patients with chronic kidney disease as high-risk groups. It is suggested that a longitudinal evaluation of antibody titers in patients with chronic kidney disease be undertaken to confirm their predictive value in the development of KS.
Global Dermatology, 2016
Introduction: Epidemic AIDS-associated Kaposi´s sarcoma (KS) is the most aggressive form of this neoplasm and is strongly associated with the reactivation of human herpesvirus type 8 (HHV-8), particularly among men who have sex with men. Objectives: To evaluate the presence of HHV-8 DNA in the biopsy smears of 31 patients with different clinical forms of AIDS-associated KS. Materials and methods: Epidemiologic, clinic, immunologic and virologic characteristics of 31 HIV infected patients with KS were included in this descriptively and retrospectively analysis from 2010 to 2013. KS was classified in four clinical forms including only cutaneous lesions, only mucosal involvement, mucocutaneous compromise and disseminated disease. The detection of DNA HHV-8 was performed by polymerase chain reaction (PCR) in all biopsy smears by tissue disruption to perform the DNA extraction, DNA purification by spectrophotometry analysis and DNA amplification with specific oligonucleated primers. Results: Thirty patients were male, the median of age was 34 years and the most frequent risk factor for HIV infection was unprotected sexual contact (90%). The median of time between HIV infections to neoplasm diagnosis was 6 years. In 11 patients (35%) KS was the first defining illness. The median of CD4 T cell count at the time of neoplasm diagnosis was 39 cell/μL. The majority of patients (84%) were not receiving highly active antiretroviral therapy (HAART). Clinical forms includes 12 patients with cutaneous KS, 8 patients with mucosal KS, 7 patients with disseminated disease and 4 patients with mucocutaneous involvement. PCR HHV-8 was positive in 24 (77%) biopsy smears. When we analyzed this group the median of age was 34 years, the median of time between HIV infection to neoplasm diagnosis was 9 years, the median the median of CD4 T cell count was 39 cell/μL and only 5 patients were receiving HAART at the time of diagnosis. No significant difference was observed between the HHV-8 positive and negative probable due to the small size of the cohort. Conclusion: Although HHV-8 DNA was detected in a high number of patients in these series, it is possible that other mechanisms may be involved in the pathogenesis of AIDS-associated KS.
PLoS ONE, 2009
Introduction: Kaposi sarcoma (KS) is the leading cause of cancer in Uganda and occurs in people with and without HIV. Human herpesvirus-8 (HHV-8) replication is important both in transmission of HHV-8 and progression to KS. We characterized the sites and frequency of HHV-8 detection in Ugandans with and without HIV and KS. Methods: Participants were enrolled into one of four groups on the basis of HIV and KS status (HIV negative/KS negative, HIV positive/KS negative, HIV negative/KS positive, and HIV positive/KS positive). Participants collected oral swabs daily and clinicians collected oral swabs, anogenital swabs, and plasma samples weekly over 4 weeks. HHV-8 DNA at each site was quantified by polymerase chain reaction (PCR).