Article

Human herpesvirus 8 presence and viral load are associated with the progression of AIDS-associated Kaposi's sarcoma

University of Oxford, Oxford, England, United Kingdom
AIDS (Impact Factor: 5.55). 08/2007; 21(12):1541-5. DOI: 10.1097/QAD.0b013e3282202b7d
Source: PubMed

ABSTRACT

We present the largest longitudinal study to date that examines the association between Kaposi's Sarcoma (KS) disease progression and the presence and viral load of human herpesvirus 8 (HHV-8).
Ninety-six men were enrolled at HIV clinics in Atlanta, Georgia, who had KS (n = 47) or were without KS but seropositive for HHV-8. Visits occurred at 6-month intervals for 2 years at which the patient's KS status was evaluated and oral fluid and blood were collected for quantification of HHV-8 DNA and antibodies.
The presence of HHV-8 DNA in blood was more common (P < 0.001) and the viral load higher (P < 0.001) in men with KS in comparison with men without KS. Mean HHV-8 viral loads in blood and oral fluids were associated with disease status, being highest among patients with progressing KS, intermediate among patients with stable KS, and lowest among patients with regressing KS. Consistent with our previous report high antibody titers to HHV-8 orf 65 were inversely associated with HHV-8 shedding in oral fluid.
We observed a significant association between changes in KS disease severity and the presence and viral load of HHV-8. HHV-8 viral load in blood may provide useful information to clinicians for assessment of the risk of further disease progression in patients with KS.

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    • "KS malignancies are AIDS defining, but rarely associated with high-level virus replication. Average KSHV plasma viral loads are 1–2 log 10 units lower than EBV or HCMV viral loads even in symptomatic patients (Laney et al., 2007;Whitby et al., 1995). Hence, for this exceptional case we considered that the patient succumbed to acute KSHV viremia. "
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    ABSTRACT: KSHV inflammatory cytokine syndrome (KICS) is a newly described condition characterized by systemic illness as a result of systemic, lytic KSHV infection. We used Illumina sequencing to establish the DNA vironome of blood from such a patient. It identified concurrent high-level viremia of human herpesvirus (HHV) 8 and 6a. The HHV8 plasma viral load was 5,300,000 copies/ml, which is the highest reported to date; this despite less than five skin lesions and no HHV8 associated lymphoma. This is the first report of systemic HHV6a/KSHV co-infection in a patient. It is the first whole genome KSHV sequence to be determined directly from patient plasma rather than cultured or biopsied tumor material. This case supports KICS as a new clinical entity associated with KSHV.
    Full-text · Article · Aug 2012 · Virology
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    • "The different rates of Kaposi sarcoma most likely reflect differences in the study populations and in observation period. Whereas 32% of patients in the French cohort were men who had sex with men (MSM), in our cohort 47% of patients were MSM, which carry an increased risk to develop Kaposi sarcoma as compared to female patients and other HIV-positive patients with different transmission risks [13-15]. Moreover, our observation time was confined to the HAART era, while Patel. "
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    ABSTRACT: To estimate the cancer risk of HIV-infected patients in the HAART era with respect to a general reference population and to determine risk factors for malignancy. Long term (1996-2009) cancer incidence of the Bonn single centre HIV cohort was compared to the incidence of the reference population of Saarland using standardized incidence ratios (SIR). Poisson regression analysis was used to identify predictors of cancer risk. 1,476 patients entered the cohort, enabling 8,772 person years of observation. 121 tumours in 114 patients, 7 in-situ and 114 invasive cancers, were identified. Malignancies associated with infectious agents such as Kaposi sarcoma (SIRs: male: 5,683; female: 277), non-Hodgkin lymphoma (SIRs male: 35; female: 18), anal cancer (SIRs male: 88; female: 115) as well a cervical carcinoma (SIR female: 4) and Hodgkin?s disease (SIR male: 39) and liver cancer (SIR male: 18) were substantially more frequent in HIV-infected patients than in the general population (p< 0.001, each), whereas all other types of cancer were not increased. Poisson regression identified HAART (incidence rate ratio IRR (95% CI): 0.28 (0.19-0.41), p<0.001), CD4 count (IRR per 100 cells/μl increase: 0.66 (0.57-0.76), p<0.001), hepatitis B (IRR: 2.15 (1.10-4.20), p = 0.046) and age (IRR per 10 year increase: 1.23 (1.03 - 1.46), p = 0.023) as independent predictors for the occurrence of any type of cancer. HAART and preserved CD4 cells preferentially reduce the risk of malignancies associated with oncogenic infections.
    Full-text · Article · Mar 2011 · European journal of medical research
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    • "Furthermore, the type of HAART regimen used did not impact response significantly. The association of HHV-8 viral load with development of new lesions or with disease progression was again demonstrated in two recent studies [45, 46]. Stebbing et al. [47] conducted a prospective cohort study to develop an easily quantifiable prognostic index for patients with AIDS-related KS. "
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    ABSTRACT: The human herpesvirus 8 (HHV-8) is the oncogenic virus associated with Kaposi's sarcoma (KS) and lymphoproliferative disorders, namely, primary effusion lymphoma and multicentric Castleman's disease. KS is among the most common malignancies seen in HIV-infected patients despite the decreased incidence of KS in the era of highly active antiretroviral therapy. Advances in molecular pathology reveal HHV-8 tumorigenesis is mediated through molecular mimicry wherein viral-encoded proteins can activate several cellular signaling cascades while evading immune surveillance. This knowledge has led to the evolution of multiple therapeutic strategies against specific molecular targets. Many such therapeutic modalities have shown activity, but none have proven to be curative. Identifying possible prognostic factors is another active area of research. This review summarizes the recent developments in the fields of virus transmission, molecular biology, and treatment of HHV-8-related neoplasms.
    Preview · Article · Mar 2010 · Current Infectious Disease Reports
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