Relationship of human herpesvirus 8 peripheral blood virus load and Kaposi's sarcoma clinical stage

Campbell, Thomas; Borok, Margaret; Gwanzura, Lovemore; MaWhinney, Samantha; White, Iréne; Ndemera, Buxton; Gudza, Ivy; Fitzpatrick, Lisa; Schooley, Robert T.

doi:10.1097/00002030-200009290-00006

Cited by 126 publications

(88 citation statements)

References 32 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…16,21 A more recent study demonstrated cell-free KSHV DNA in the circulation of most HIV-1/KSHV-coinfected subjects regardless of KS disease status. 22 These results further suggest that KSHV frequently replicates and expresses vIL-6 in some tissue other than the KS lesions in KSHV-infected HIV ϩ patients.…”

Section: Resultsmentioning

confidence: 66%

Detection of viral interleukin-6 in Kaposi sarcoma–associated herpesvirus–linked disorders

Aoki

Yarchoan

Wyvill

et al. 2001

Blood

View full text Add to dashboard Cite

Section: Resultsmentioning

confidence: 66%

Detection of viral interleukin-6 in Kaposi sarcoma–associated herpesvirus–linked disorders

Aoki

Yarchoan

Wyvill

et al. 2001

Blood

View full text Add to dashboard Cite

“…Keywords: Kaposi's sarcoma, highly active antiretroviral therapy, Uganda, sub-Saharan Africa, mortality, HIV [5][6][7]. However, HAART has changed the natural history of AIDS-associated KS in industrialized countries since its introduction more than a decade ago.…”

Section: Resultsmentioning

confidence: 99%

Clinical outcomes of HIV‐infected patients with Kaposi's sarcoma receiving nonnucleoside reverse transcriptase inhibitor‐based antiretroviral therapy in Uganda

et al. 2011

View full text Add to dashboard Cite

BackgroundClinical outcomes for patients with Kaposi's sarcoma (KS) using nonnucleoside reverse transcriptase inhibitor (NNRTI)-based highly active antiretroviral therapy (HAART) in resource-limited settings have not previously been described. MethodsWe evaluated HIV-infected patients aged Ն 18 years, who initiated HAART in the Home-Based AIDS Care (HBAC) project in Tororo, Uganda, between May 2003 and February 2008 and were diagnosed with KS at baseline or during follow-up. We examined independent risk factors for having either prevalent or incident KS and risk factors for death among patients with KS. ResultsOf 1121 study subjects, 17 (1.5%) were diagnosed with prevalent KS and 18 (1.6%) with incident KS over a median of 56.1 months of follow-up. KS was associated with male sex [adjusted odds ratio (AOR) 2.41; 95% confidence interval (CI) 1.20-4.86] and baseline CD4 cell count < 50 cells/mL (AOR 3.25; 95% CI 1.03-10.3). Eleven (65%) of 17 patients with prevalent KS and 13 (72%) of 18 patients with incident KS experienced complete regression (P = 0.137). Eighteen (64%) of 28 patients who remained on NNRTI-based HAART experienced regression of their KS and six (86%) of seven patients who were switched to protease inhibitor-containing HAART regimens had regression of their KS (P = 0.23). Mortality among those with KS was significantly associated with visceral disease (hazard ratio 19.22; 95% CI 2.42-152). ConclusionPrevalent or incident KS was associated with 30% mortality. The resolution of KS lesions among individuals who initiated HAART with NNRTI-based regimens was similar to that found in studies using only protease inhibitor-based HAART.Keywords: Kaposi's sarcoma, highly active antiretroviral therapy, Uganda, sub-Saharan Africa, mortality, HIV [5][6][7]. However, HAART has changed the natural history of AIDS-associated KS in industrialized countries since its introduction more than a decade ago. For HIV-infected individuals with KS in industrialized countries, HAART results in the regression of the size and number of existing lesions [8,9]. At the population level, the use of HAART has been associated with a decreased proportion of new AIDS-related cancers, with a 30-50% reduction in KS incidence in both the USA and Europe [10].Most studies examining the clinical effects of HAART on KS have come from high-income countries and from clinic cohorts where protease inhibitor (PI)-based regimens predominated The clinical effects of HAART on AIDSassociated KS in African countries, where programmes primarily use nonnucleoside reverse transcriptase inhibitor (NNRTI)-based therapy, is not known. To address this question we analysed data collected from individuals with HIV infection receiving NNRTI-based antiretroviral therapy in rural Uganda as part of a randomized clinical trial [11]. We examined factors associated with the diagnosis of KS at baseline and during follow-up and determined which factors were associated with mortality among patients with KS. Methodology Study settingThe Home-Based AIDS Care (HBAC) prog...

show abstract

“…Several studies have shown an association of DNA positivity and higher levels of HHV-8 DNA in blood and tissues with development of KS and other HHV-8-related diseases. [52][53][54][55][56] We hypothesize that such viral replication may boost CD8 ϩ T-cell responses against HHV-8 lytic cycle proteins. This T-cell reactivity in turn acts to quell viral replication and prevent development of disease.…”

Section: Discussionmentioning

confidence: 99%

Identification of an HLA A*0201–restricted CD8+T-cell epitope for the glycoprotein B homolog of human herpesvirus 8

Wang

Huang

Rappocciolo

et al. 2002

Blood

View full text Add to dashboard Cite

IntroductionHuman herpesvirus 8 (HHV-8; also termed Kaposi sarcomaassociated herpesvirus) is a gammaherpesvirus that is considered to be the causative agent of Kaposi sarcoma (KS), body cavity B-cell lymphoma, and multicentric Castleman disease. 1 T-cell immunity is thought to play an important role in control of HHV-8 infection and these associated diseases. [2][3][4][5] In this regard, we 2,3 and others 4 have demonstrated that major histocompatibility complex (MHC) class I-restricted, CD8 ϩ cytotoxic T lymphocytes (CTLs), and interferon ␥ (IFN-␥) responses are detectable in peripheral blood mononuclear cells (PBMCs) of HHV-8 ϩ individuals using recombinant vaccinia viruses expressing HHV-8 lytic and latent cycle proteins. These anti-HHV-8 T-cell responses are lower during human immunodeficiency virus type 1 (HIV-1) infection and may be involved in prevention of KS and other HHV-8-associated diseases.Support for the potential role of CD8 ϩ T-cell immunity in control of HHV-8 infection comes from several studies on immune control of acute and persistent infections with 2 other gammaherpesviruses, specifically, Epstein-Barr virus (EBV) and murine herpesvirus 68 (MHV-68). 6-10 Although EBV latency proteins can induce strong CD8 ϩ T-cell responses, 11 lytic cycle proteins are considered as major CD8 ϩ T-cell targets in both acute and persistent EBV infections. 12 Immunodominant epitopes restricted to different HLA class I alleles, which are important for our understanding of viral immunopathogenesis and development of appropriate vaccines, 13 have been determined for peptides derived from EBV structural proteins gp350 and gp85, and immediate-early (IE) and early proteins such as BZLF1, BRLF1, and BMLF1. [6][7][8][9] Compared to latency proteins, the frequency of CD8 ϩ T lymphocytes specific for peptides derived from lytic cycle proteins is higher in PBMCs of healthy virus carriers. 14 CD8 ϩ CTLs have also been demonstrated to secrete IFN-␥ in response to EBV lytic cycle antigens in seropositive individuals. 15 During primary EBV infectious mononucleosis, up to 60% of CD8 ϩ T cells circulating in blood are EBV-specific. 16 Furthermore, by use of a peptide-tetramer complex, Tan et al 17 have directly visualized from 0.5% to 6.6% of CD8 ϩ T blood cells in virus carriers that are specific for a single BMLF-1 epitope.In MHV-68 infection, lytic cycle proteins also induce CD8 ϩ T cell responses. 10,18,19 T cells specific for peptides derived from lytic cycle proteins dominate the acute phase of MHV-68 infection. 10,19 Moreover, vaccination with immunodominant CD8 ϩ T-cell epitopes derived from lytic cycle proteins of MHV-68 significantly reduces viral titers and the level of infected cells during acute infection. 20 We have tested CD8 ϩ T-cell reactivity to peptides derived from 5 HHV-8 lytic cycle proteins based on a prediction model for the HLA A*0201 motif in HHV-8-infected subjects to determine immunodominant epitopes to the virus. We chose HLA A*0201 because it is prevalent in a large percentage of the white populat...

show abstract

Relationship of human herpesvirus 8 peripheral blood virus load and Kaposi's sarcoma clinical stage

Abstract: 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.

Cited by 126 publications

References 32 publications

Detection of viral interleukin-6 in Kaposi sarcoma–associated herpesvirus–linked disorders

Detection of viral interleukin-6 in Kaposi sarcoma–associated herpesvirus–linked disorders

Clinical outcomes of HIV‐infected patients with Kaposi's sarcoma receiving nonnucleoside reverse transcriptase inhibitor‐based antiretroviral therapy in Uganda

Identification of an HLA A*0201–restricted CD8+T-cell epitope for the glycoprotein B homolog of human herpesvirus 8

Contact Info

Product

Resources

About