Kaposi's Sarcoma In HIV-infected Patients Research Articles

Malignant Vascular Tumors of the Liver in Adults.

Hepatic angiosarcoma and epithelioid hemangioendothelioma (EHE) might be clinically considered a spectrum since, although more frequently presenting indolent behavior, EHE occasionally evolves to high-grade neoplasms. However, in most circumstances, pathological and immunohistochemical patterns define this differential diagnosis. More recently, molecular pathways for angiosarcoma and for EHE from other organs and from soft tissue have been proved different, paving the way for future morpho-molecular assessment of their hepatic counterpart. The frequency of liver involvement by Kaposi sarcoma in HIV-infected patients is lower nowadays. Histological findings and immunostaining for HHV-8 Ag are characteristic. Hepatic small vessel neoplasms have been recently recognized as important mimickers of angiosarcoma. The criteria for this differential diagnosis and the clinical behavior, up to now considered favorable, must be further studied.

Determinants of Kaposi Sarcoma during HIV infection: A nested case-control study from Yaoundé, Cameroon.

Although the burden of Kaposi sarcoma (KS) is fast increasing among HIV-infected populations, there is still critical lack of knowledge on its related driving factors in Cameroon. This study purposed to determine risk factors for KS in HIV-infected patients living in Yaoundé, Cameroon. This was a 1:3 case-control study nested on a retrospective cohort study, carried-out over a period of 16yearsat the Yaoundé Central Hospital, Cameroon. Cases were HIV-infected patients, diagnosed with KS after histological confirmation. Controls were HIV-infected patients, naive of KS and paired to cases through age and sex. Logistic regression analyses served to identify risk factors for KS. Of 14,220 files reviewed, 316 cases of KS (2.2%) were identified. We included 266 cases (55% males), to whom 798 controls were paired. The mean age of patients was 37.7±9.6 years. Results of multivariable logistic regression analysis identified diabetes [adjusted odds ratio (aOR) 2.9, 95%CI: 1.3-7.7; p=0.028] and HIV-related prurigo [aOR 0.3, 95%CI: 0.1-0.7; p=0.010] as factors impacting significantly KS occurrence in this study. KS is frequent among our HIV-infected patients. Those having diabetes seem at increased odds of developing KS.

Endoscopic Appearance of Oropharyngeal and Upper GI Kaposiʼs Sarcoma in an Immunocompromised Patient: A Case Report

Introduction: Kaposi's Sarcoma (KS) usually manifests as a cutaneous disease but GI mucosal manifestation are often rare. It is associated with human herpes virus-8 infection (HHV-8) and often seen in immune-compromised patients. In the USA, the widespread use of highly active anti-viral therapy (HAART) as drastically reduced the incidence of KS in HIV-infected patients. Here we present a case of oropharyngeal manifestations of Kaposi Sarcoma in a patient with HIV Case Report: A 65 year old male with history of human immunodeficiency virus (HIV) was admitted to the intensive care unit (ICU) after having a cardiopulmonary arriest secondary to hyperkalemia 7.5 meq/L. Following the placement of orogastric and endotracheal tube (ETT), significant amount of blood was noticed in the ETT. Hemoglobin was found to have trended downwards from 9.6 mg/dL to 6.7 mg/dL over the following five days. Stool guaiac was found to be positive for occult blood. Esophagogastroduodenoscopy (EGD) was initially performed and revealed multiple large hyper-vascularized violaceous submucosal nodular lesions with stigmata of recent bleeding seen on the soft palate, pharynx and within the crico-pharyngeal area close to the vocal cords. No active bleeding was noted. Examination of the distal esophagus revealed a severe ulceration with a small hiatal hernia. Biopsy of soft palate lesions showed proliferation of neoplastic spindle shaped cells arranged in bundles with slit-like capillary spaced containing erythrocytes which is consistent with Kaposi sarcoma. Biopsy was also positive for HHV-8. Colonoscopy was unremarkable for similar lesions, polyps or diverticulosis. There were no cutaneous manifestations of the disease. Conclusion: GI involvement of Kaposi sarcoma must be considered in immune-compromised patients and can be confirmed by endoscopic methods.

Relapse of Kaposi's Sarcoma and HHV-8 viremia in an HIV-infected patient switching from protease inhibitor to integrase inhibitor-based antiretroviral therapy

Combination antiretroviral therapy (cART) reduced the incidence of Kaposi's Sarcoma (KS), mainly mediated by the suppression of HIV replication and the recovery of the immune system. The effect of specific classes of antiretrovirals on KS remains unclear. However, both in vitro and clinical studies provided evidences that protease inhibitors (PI) can inhibit Human Herpesvirus 8 (HHV-8) replication and reduce KS risk and progression. Moreover, relapses of KS in HIV-infected patients switching from a PI to a non-nucleoside reverse transcriptase inhibitor-based cART have been reported. We describe here the case of a patient who experienced a relapse of KS and a rebound of HHV-8 viremia two months after switching from a PI to an integrase inhibitor-based cART.

Incidence rate of Kaposi sarcoma in HIV-infected patients on antiretroviral therapy in Southern Africa: a prospective multicohort study.

The risk of Kaposi sarcoma (KS) among HIV-infected persons on antiretroviral therapy (ART) is not well defined in resource-limited settings. We studied KS incidence rates and associated risk factors in children and adults on ART in Southern Africa. We included patient data of 6 ART programs in Botswana, South Africa, Zambia, and Zimbabwe. We estimated KS incidence rates in patients on ART measuring time from 30 days after ART initiation to KS diagnosis, last follow-up visit, or death. We assessed risk factors (age, sex, calendar year, WHO stage, tuberculosis, and CD4 counts) using Cox models. We analyzed data from 173,245 patients (61% female, 8% children aged <16 years) who started ART between 2004 and 2010. Five hundred and sixty-four incident cases were diagnosed during 343,927 person-years (pys). The overall KS incidence rate was 164/100,000 pys [95% confidence interval (CI): 151 to 178]. The incidence rate was highest 30-90 days after ART initiation (413/100,000 pys; 95% CI: 342 to 497) and declined thereafter [86/100,000 pys (95% CI: 71 to 105), >2 years after ART initiation]. Male sex [adjusted hazard ratio (HR): 1.34; 95% CI: 1.12 to 1.61], low current CD4 counts (≥500 versus <50 cells/μL, adjusted HR: 0.36; 95% CI: 0.23 to 0.55), and age (5-9 years versus 30-39 years, adjusted HR: 0.20; 95% CI: 0.05 to 0.79) were relevant risk factors for developing KS. Despite ART, KS risk in HIV-infected persons in Southern Africa remains high. Early HIV testing and maintaining high CD4 counts is needed to further reduce KS-related morbidity and mortality.

Kaposi's Sarcoma in HIV-infected patients in South Africa: Multicohort study in the antiretroviral therapy era.

The incidence of Kaposi's Sarcoma (KS) is high in South Africa but the impact of antiretroviral therapy (ART) is not well defined. We examined incidence and survival of KS in HIV-infected patients enrolled in South African ART programs. We analyzed data of three ART programs: Khayelitsha township and Tygerberg Hospital programs in Cape Town and Themba Lethu program in Johannesburg. We included patients aged >16 years. ART was defined as a regimen of at least three drugs. We estimated incidence rates of KS for patients on ART and not on ART. We calculated Cox models adjusted for age, sex and time-updated CD4 cell counts and HIV-1 RNA. A total of 18,254 patients (median age 34.5 years, 64% female, median CD4 cell count at enrolment 105 cells/μL) were included. During 37,488 person-years follow-up 162 patients developed KS. The incidence was 1,682/100,000 person-years (95% confidence interval [CI] 1,406-2,011) among patients not receiving ART and 138/100,000 person-years (95% CI 102-187) among patients on ART. The adjusted hazard ratio comparing time on ART with time not on ART was 0.19 (95% CI 0.13-0.28). Low CD4 cell counts (time-updated) and male sex were also associated with KS. Estimated survival of KS patients at one year was 72.2% (95% CI 64.9-80.2) and higher in men than in women. The incidence of KS is substantially lower on ART than not on ART. Timely initiation of ART is essential to prevent KS and KS-associated morbidity and mortality in South Africa and other regions in Africa with a high burden of HIV.

Characteristics of Kaposi sarcoma in HIV-infected patients

Objective: to describe clinical and laboratory characteristics; to assess predictors for death in HIV-infected patients with Kaposi sarcoma (KS). We performed a retrospective study of HIV-infected patients diagnosed with KS in one infectious diseases hospital in Romania, between January 2008-November 2013. KS diagnosis was established on physical examination, skin biopsy, and for visceral involvement upper gastrointestinal endoscopy, bronchoscopy and computed tomography. KS was staged according to the AIDS Clinical Trials Group (ACTG) [1] and the Mitsuyasu classification system [2]. We identified 27 HIV-infected patients with KS. The median age was 42 years (IQR 34-52) and 18 (67%) were male. The median CD4 count at HIV diagnosis was 195 cells/cmm (IQR 55-313), while at KS diagnosis the median CD4 count was 101 cells/cmm (IQR 41-270). Eighteen (67%) patients had a CD4 count <200 cells/cmm. The median HIV viral load at the time of KS diagnosis was 120,000 copies/mL (IQR 316-328,522). HIV infection was diagnosed before KS in 19 patients (70%), with a median time between HIV and KS diagnosis of 7 months (IQR 0-58). The most frequent KS localization was the lower limb in 16 (59%) patients and 7 (26%) patients had disseminated KS. Oral, gastrointestinal and pulmonary involvements were seen in 10 (37%), 4 (15%) and 3 (11%) patients respectively. Concomitant opportunistic infections were diagnosed in 20 (74%), while other malignancies in 3 (12%) patients. According to the ACTG classification 16 (59%) patients had poor risk KS. Fifteen (56%), 6 (22%), 1 (4%) and 5 (18%) were in stage 1, 2, 3 and 4, respectively according to the Mitsuyasu classification. Six (22%) patients received specific KS treatment: three local radiotherapy and three systemic therapy (two with interferon; one with liposomal doxorubicin). The overall mortality was 41% with a median duration between KS diagnosis and death of 6 months (IQR 2-15). Gastrointestinal involvement (p=0.019), poor-risk KS in ACTG classification (p<0.001) and stage IV Mitsuyasu (p=0.006) were associated with death in univariate analysis. The mortality rate in this study was high, due to poor immunological status, extended KS and high incidence of opportunistic infections, but also due to the lack of specific systemic treatment.

Towards a better understanding of Kaposi sarcoma-associated immune reconstitution inflammatory syndrome

Towards a better understanding of Kaposi sarcoma-associated immune reconstitution inflammatory syndrome

Pulmonary Kaposi Sarcoma in AIDS

A 34-year-old man presented to the hospital with a productive cough, dyspnea, subjective fever, chills, and myalgias. Fever, tachycardia, tachypnea, and severe hypoxemia were noted on arrival. Examination revealed a frail, diaphoretic man in considerable respiratory distress, with diffuse bilateral rales and rhonchi; a violaceous, raised rash over the limbs and trunk was also noted. Findings on chest radiography were suggestive of multilobar pneumonia. A rapid oral antibody test for human immunodeficiency virus (HIV) returned a positive result. Computed tomography of the chest showed striking flame-shaped opacities and spicular thickening of the bronchovascular bundles in all lobes (panels A, B, and C, arrows). These findings are characteristic of pulmonary Kaposi sarcoma (KS).1 In our patient, the diagnosis was confirmed by bronchoscopy and skin biopsy. Computed tomographic features of KS are extremely helpful in guiding the initial management of HIV-infected patients presenting with symptoms of pneumonia. Kaposi sarcoma in HIV-infected patients is diagnostic of AIDS. The goals of therapy in AIDS-associated pulmonary KS are prevention of progression and reduction of tumor burden. Initial management consists of highly active antiretroviral therapy, as this is associated with lesion regression and prolonged survival.2 After optimizing highly active antiretroviral therapy, systemic chemotherapy can be initiated for pulmonary KS. Single-agent chemotherapy can include liposomal doxorubicin, liposomal daunorubicin, paclitaxel, or etoposide. Various combination chemotherapy regimens have been studied and may provide higher response rates compared with single agents.3 Immunosuppression remains a major concern with the use of these agents in patients with AIDS-associated KS. Antiviral therapy directed against human herpesvirus 8 have shown variable success.4 Agents such as interleukin 12 and a variety of angiogenesis inhibitors are under investigation as potential therapies. Our patient initially received noninvasive positive pressure ventilation. He subsequently had worsening respiratory failure and required endotracheal intubation. Until the diagnosis of KS was confirmed, the patient was treated with broad-spectrum antibiotics for severe community-acquired pneumonia as well as coverage for Pneumocystis jirovecii pneumonia. Highly active antiretroviral therapy, in the form of emtricitabine, tenofovir, and efavirenz was administered after stabilization. The patient's respiratory status improved over the following days, and he was successfully extubated and transferred to the medical floor. He experienced a prolonged hospital course that was complicated by suspected immune reconstitution inflammatory syndrome and hospital-acquired pneumonia. Eventually, he was given valganciclovir, doxorubicin, and vinblastine for treatment of KS, but he died after developing overwhelming sepsis.

Incidence of Kaposi Sarcoma in HIV-infected patients – a prospective multi-cohort study from Southern Africa

Oral presentation presented at the 13th International Conference on Malignancies in AIDS and Other Acquired Immunodeficiencies (ICMAOI) Bethesda, MD, USA. 7-8 November 2011

Incidence of Kaposi sarcoma in HIV-infected patients receiving antiretroviral therapy: A prospective multicohort study from southern Africa.

1589 Background: The incidence of Kaposi sarcoma (KS) is high in Southern Africa: KS is the most common cancer in HIV-infected persons. Data on KS in patients receiving antiretroviral therapy (ART) are, however, scarce in Africa. Within the framework of a large multi-cohort project, the International epidemiologic Database to Evaluate AIDS (IeDEA), we studied the incidence and risk factors for the development of KS in HIV-infected patients starting ART in Southern Africa. Methods: We analyzed prospectively collected data of HIV-infected patients who started ART with three antiretroviral drugs from at least two classes. Prevalent KS cases diagnosed before or at start of ART were excluded. Incidence rates and 95% confidence intervals (CI) were calculated based on the Poisson distribution; risk factors were estimated using crude and adjusted Cox models. Hazard ratios (HR) with 95% CI and medians with interquartile ranges (IQR) are presented. Results: 185,924 patients from 7 cohort studies in Botswana, Mozambique, South Africa, Zambia, Zimbabwe with 376,630 person-years of follow-up were included. At start of ART median age was 34 years (IQR 28–41) and median CD4 cell count 145 cells/µl (IQR 73-225). 61% of patients were female. A total of 601 incident KS cases were recorded. The incidence for KS in patients on ART was 160 (95% CI 147-173) per 100,000 person-years. The risk for KS increased with age. Adjusting for age, gender, WHO stage and CD4 cell count adults >40 years had a more than ten-fold increased risk for developing KS compared to infants (HR 11.8, 95% CI 3.0-46.2); men were more likely to develop KS compared to women (HR 1.4, 95% CI 1.1-1.7) and the risk to develop KS was increased in patients with AIDS at start ART (WHO stage IV vs. I: HR 2.2, 95% CI 1.6-3.1). Conclusions: In Southern African countries with a high prevalence of HHV-8 the risk to develop KS in HIV infected patients receiving ART increases steeply with age and is higher in patients with more advanced HIV infection.

The absence of Tat sequences in tissues of HIV-negative patients with epidemic Kaposi's sarcoma.

Tat, an essential regulatory protein of HIV, acts as a growth factor for Kaposi's sarcoma (KS)-derived cells in culture. We tested the hypothesis that HIV-negative epidemic KS patients who are also at high risk for HIV disease might have been infected with a defective HIV-1 virus that retained the ability to express Tat. We evaluated the presence of Tat sequences in KS tissue and peripheral blood mononuclear cells (PBMC) of HIV-1-negative individuals with epidemic KS who had risk factors for HIV infection by polymerase chain reaction using specific primers for the Tat region of HIV-1. No evidence for the presence of Tat-1 sequences or for Tat-expressing defective HIV-1 virus was found. These results suggest that HIV-1 Tat does not play a role in the initiation of KS in HIV-1-negative individuals. Tat might play an indirect role in epidemic KS in HIV-infected patients.