Proposal of model for personalized early adapted cancer screening in people living with HIV: experience of "Gaetano Martino" Hospital University of Messina.

Human immunodeficiency virus (HIV) infection has historically been related to the development of specific cancers, some of which are so closely linked to the infection, such as Kaposi's Sarcoma (KS), that they have earned the name Acquired Immuno-Deficiency Syndrome (AIDS)-defining cancers (ADCs). While the development of antiretroviral therapy (ART) has decreased the incidence of AIDS-defining cancers, the resulting aging of people living with HIV (PLWH) highlighted an increased occurrence of other forms of cancer. At the "Gaetano Martino" hospital in Messina, we developed a multidisciplinary approach by creating a bridge between the Oncology Unit and the Infectious Diseases Unit to carry out screening and a more rapid diagnostic and therapeutic journey for cancers in PLWH. The goal is to improve the diagnosis of various types of cancer by involving other professionals, such as gastroenterologists and gynecologists, to ensure faster access to treatment and, therefore, a greater chance of survival. In addition, our multidisciplinary approach has also included vaccine screening, offered by the "Gaetano Martino" hospital and useful for preventing the development of specific forms of cancer in the entire population and particularly in PLWH.

Soft tissue tumours of the penis. The 30-year Istituto Nazionale Tumori di Milano experience.

Objective: Small series and individual cases of penile soft tissue tumours are reported in the literature: these are rare tumours that represent less than 5% of all penile tumours. Methods: Penile soft tissue tumours were collected from the archive of the Department of Pathology at the Istituto Nazionale dei Tumori of Milan between January 1990 and October 2021. All available medical records were retrieved and reviewed to obtain clinical information. Results: Our series refers to the 30-year experience of highlighting the heterogeneity in the presentation and microscopic features of these rare sarcomas. 18 penile soft tissue tumours are described, 4 benign and 14 malignant. The mean age at diagnosis was 58.2 years (range 24-96 years) and 53.6 years among malignancies (range 24-89). The most frequent histotype was Kaposi's sarcoma (nr = 4) and very unusual histotypes were observed, namely low-grade fibromyxoid sarcoma, synovial sarcoma, proximal type epithelioid sarcoma and the first reported case of dedifferentiated liposarcoma of the penis. Conclusions: Among sarcomas of the genitourinary tract, tumours of the soft tissues of the penis are the rarest. Penile sarcomas can present at a young age. Kaposi's sarcoma in HIV-negative patients has a favorable outcome, while deep sarcomas have an aggressive behavior and poor prognosis.

Reactivation of Kaposi's sarcoma-associated herpesvirus (KSHV) by SARS-CoV-2 in non-hospitalised HIV-infected patients.

BACKGROUND: While acute SARS-CoV-2 infection and associated inflammation resulted in substantial morbidity and mortality during the COVID-19 pandemic, particularly in unvaccinated patients, long-term effects of SARS-CoV-2 exposure for reactivation of latent oncogenic herpesviruses, such as KSHV, is unknown. METHODS: We performed a longitudinal observational cross-sectional study on 407 non-hospitalised adult HIV-infected (CD4 count <350 cells/µL) patients attending antiretroviral therapy services in Gugulethu, South Africa, from October 2020 to April 2023. FINDINGS: KSHV seroprevalence was 53.5%; the quarterly SARS-CoV-2 seroprevalence increased from 76.2% (before roll-out of COVID-19 vaccinations) to 94.9%, with 32.2% being self-reportedly vaccinated against COVID-19. Over the course of recruitment, the quarterly percentage of patients with detectable KSHV viral load (VL) in the peripheral blood increased from 3.3% to 69.2%. The presence of KSHV VL was significantly associated with SARS-CoV-2 RBD antibody titers in unvaccinated (median RBD IgG OD 1.24 [IQR 0.82-2.42] in non-reactivated versus 2.83 [IQR 1.08-4.72] in reactivated patients, p = 0.0030) but not in vaccinated patients (median RBD IgG OD 5.13 [IQR 4.11-6.36] in non-reactivated versus 4.53 [IQR 2.90-5.92] in reactivated patients, p = 0.086). Further logistic regression revealed significantly higher odds of KSHV reactivation in unvaccinated, previously SARS-CoV-2 exposed patients (p = 0.015, adjusted OR 1.28 [95% CI: 1.05-1.55]), but not vaccinated patients (p = 0.080, adjusted OR 0.83 [95% CI: 0.67-1.02]). Interestingly, detectable KSHV VL was not associated with increased inflammatory markers such as C-reactive protein and interleukin-6. INTERPRETATION: High, and most likely repeated, exposure to SARS-CoV-2 in unvaccinated individuals may have long-term consequences for reactivation of KSHV infection as shown here in the context of HIV-infected patients with impaired immune functions. Post-pandemic prevention and/or monitoring strategies of potential KSHV-associated pathologies in high-risk patients with immunodeficiencies are therefore highly recommended. FUNDING: This research was funded by the EDCTP2 programme (Training and Mobility Action TMA2018SF-2446).

Real-world use of antiretroviral therapy and risk of cancer among people with HIV in Texas.

BACKGROUND: Combination antiretroviral therapy (cART) may reduce cancer risk among people with HIV (PWH), but cancer-specific associations are incompletely understood. METHODS: We linked HIV and cancer registries in Texas to a national prescription claims database. cART use was quantified as the proportion of days covered (PDC). Cox proportional hazards models assessed associations of cancer risk with cART usage, adjusting for demographic characteristics, AIDS status, and time since HIV report. RESULTS: We evaluated 63 694 PWH followed for 276 804 person-years. The median cART PDC was 21.4% (interquartile range: 0.0-59.8%). cART use was associated with reduced risk of Kaposi sarcoma [adjusted hazard ratio (aHR) 0.48, 95% confidence interval (CI) 0.34-0.68 relative to unexposed status] and non-Hodgkin lymphoma (aHR 0.41, 95% CI 0.31-0.53), liver cancer (aHR 0.61, 95% CI 0.39-0.96), anal cancer (aHR 0.65, 95% CI 0.46-0.92), and a miscellaneous group of 'other' cancers (aHR 0.80, 95% CI 0.66-0.98). In contrast, cART-exposed status was not associated with risk for cervical, lung, colorectal, prostate or breast cancers. CONCLUSION: In a large HIV cohort incorporating data from prescription claims, cART was associated with greatly reduced risks of Kaposi sarcoma and non-Hodgkin lymphoma, and to a lesser degree, reduced risks of liver and anal cancers. These associations likely reflect the beneficial effects of HIV suppression and improved immune control of oncogenic viruses. Efforts to increase cART use and adherence may further decrease cancer incidence among PWH.

Skin cancer risk in people living with HIV: a call for action.

A diagnosis of HIV poses secondary medical risks to patients, ranging from infections to neoplastic conditions. Regarding skin cancer, these risks extend beyond the well known association with Kaposi sarcoma and include Merkel cell carcinoma, squamous cell carcinoma, and high-risk melanomas. Despite evidence of these risks, knowledge and awareness remain low, among care providers for people living with HIV, individual patients, and even some specialists in dermatology. Crucially, medical organisations do not adequately address this concern, as there is an absence of treatment guidelines for the screening and management of skin cancer for people living with HIV. To continue providing high-quality care for this population, the increased risk of multiple high-risk skin cancers needs to be appropriately recognised by both providers and patients. Accordingly, we call for renewed emphasis on patient education and implementation of improved organisational guidelines for skin cancer screening protocols.

Prognostic factors for competing risk in patients with AIDS-related Kaposi's sarcoma: A SEER population-based study.

OBJECTIVES: Despite the improved survival of patients with AIDS and Kaposi's sarcoma (KS), competing events are a non-negligible issue affecting the survival of such patients. In this study, we explored the prognostic factors of KS-specific and non-KS-specific mortality in patients with AIDS-related KS (AIDS-KS), accounting for competing risk. METHODS: We identified 17 103 patients with AIDS-KS aged 18-65 years between 1980 and 2016 from the Surveillance, Epidemiology, and End Results (SEER) 18 registry database. Prognostic factors for KS-specific and non-KS-specific mortality were determined by the Fine and Grey proportional subdistribution hazard model. We built competing risk nomograms and assessed their predictive performance based on the identified prognostic factors. RESULTS: In total, 12 943 (75.68%) patients died, 1965 (15.50%) of whom died from competing events. The KS-specific mortality rate was 14 835 per 100 000 person-years, and the non-KS specific mortality rate was 2719 per 100 000 person-years. Specifically, age >44 years was associated with an 11% decrease in the subdistribution hazard of KS-specific mortality compared with age <43 years but a 50% increase in the subdistribution hazard of non-KS-specific mortality. Being male was associated with a 26% increase in the subdistribution hazard of KS-specific mortality compared with being female but a 32% decrease in the subdistribution hazard of non-KS-specific mortality. Notably, being in the antiretroviral therapy (ART) era consistently showed a decrease in the subdistribution hazard of both KS-specific and non-KS-specific mortality than being in the pre-ART era. CONCLUSIONS: Competing events commonly occurred among patients with AIDS-KS, which deserves further attention to improve the prognosis of these patients.

Outcomes in Kaposi's sarcoma-associated herpesvirus -associated primary effusion lymphoma and multicentric Castleman's disease in patients with human immunodeficiency virus (HIV) in a safety-net hospital system.

OBJECTIVE: To describe cases of Kaposi's sarcoma-associated herpesvirus (KSHV)-associated multicentric Castleman's disease (MCD) and primary effusion lymphoma (PEL) in patients with HIV from a large, safety-net hospital system in Dallas, Texas, USA. METHODS: We conducted a retrospective review of patients with HIV-associated PEL and/or MCD. RESULTS: Twelve patients with PEL and 10 patients with MCD were identified. All patients were male and 17 of 20 were men who have sex with men; 66.7% of PEL patients and 50% of MCD patients had concurrent KS at the time of diagnosis; 42% of patients with PEL and 20% of patients with MCD died during the follow-up period. We noted improved survival in our cohort compared to previous studies, particularly in our PEL patients with a median survival of 11.4 months compared to 3-6-month median survival historically. Median follow-up time for MCD patients was 17.5 months. This improved survival is despite suboptimal antiretroviral therapy (ART) adherence at diagnosis, with only 50% of patients on ART at the time of MCD/PEL diagnosis. CONCLUSION: These data highlight the importance of early recognition of PEL and MCD, and the larger-scale efforts needed to better understand the pathogenetic drivers of clinical outcomes in patients affected by KSHV-related diseases.

Survival of patients living with HIV and cancer in Cali, Colombia.

Background: People living with HIV have an increased risk of cancer compared to the general population. However, with the increase in life expectancy and advances in antiretroviral therapy, the survival of patients with cancer and HIV has changed. Objective: To determine the survival of patients living with HIV and cancer in Cali, Colombia. Methods: A retrospective cohort study was conducted at the Fundación Valle del Lili, Cali, Colombia. Data from the HIV database was crossed with data from the hospital and population-based cancer registries between 2011-2019. Patients <18 years, limited available clinical information on the diagnosis and treatment of HIV and cancer, and non-oncological tumor diagnosis were excluded. Results: A total of 173 patients were included. The frequencies of AIDS-defining neoplasms were: Non-Hodgkin lymphoma (42.8%), Kaposi sarcoma (27.8%), and cervical cancer (4.6%). Overall survival was 76.4% (95% CI 68.9-82.3) at five years. Poorer survival was found in patients with AIDS-defining infections (56.9% vs. 77.8%, p=0.027) and non-AIDS-defining infections (57.8% vs. 84.2%, p=0.013), while there was better survival in patients who received antiretroviral therapy (65.9% vs. 17.9%, p=0.021) and oncological treatment (66.7% vs. 35.4%, p<0.001). The presence of non-AIDS-defining infections increases the risk of dying (HR = 2.39, 95% CI 1.05-5.46, p=0.038), while oncological treatment decreases it (HR = 0.33, 95% CI 0.14-0.80, p=0.014). Conclusions: In people living with HIV, Non-Hodgkin lymphoma and Kaposi sarcoma are the most common neoplasms. Factors such as AIDS-associated and non-AIDS-associated infections have been identified as determinants of survival. Cancer treatment seems to improve survival.

Antecedentes: Las personas que viven con VIH tienen un riesgo mayor de cáncer en comparación con la población general. Sin embargo, con el aumento de la esperanza de vida y los avances en la terapia antirretroviral, la supervivencia de los pacientes con cáncer y VIH ha cambiado. Objetivo: Determinar la supervivencia de los pacientes que viven con VIH y cáncer en Cali, Colombia. Métodos: Se realizó un estudio de cohorte retrospectivo en la Fundación Valle del Lili, Cali, Colombia. Los datos de la base de datos de VIH se cruzaron con los datos de los registros de cáncer de base hospitalaria y poblacional entre 2011-2019. Se excluyeron los pacientes <18 años, con información clínica limitada disponible sobre el diagnóstico y tratamiento del VIH y el cáncer y los casos con diagnóstico de tumor no oncológico. Resultados: Se incluyeron un total de 173 pacientes. Las frecuencias de neoplasias definitorias de SIDA fueron: linfoma no Hodgkin (42.8%), sarcoma de Kaposi (27.8%) y cáncer cervical (4.6%). La supervivencia global fue del 76.4% (IC 95% 68.9-82.3) a los cinco años. Se encontró una peor supervivencia en pacientes con infecciones definitorias de SIDA (56.9% vs. 77.8%, p=0.027) e infecciones no definitorias de SIDA (57.8% vs. 84.2%, p=0.013), mientras que hubo una mejor supervivencia en pacientes que recibieron terapia antirretroviral (65.9% vs. 17.9%, p=0.021) y tratamiento oncológico (66.7% vs. 35.4%, p<0.001). La presencia de infecciones no definitorias de SIDA aumentó el riesgo de morir (HR = 2.39, IC 95% 1.05-5.46, p=0.038), mientras que el tratamiento oncológico lo disminuyó (HR = 0.33, IC 95% 0.14-0.80, p=0.014). Conclusiones: En las personas que viven con VIH, el linfoma no Hodgkin y el sarcoma de Kaposi son las neoplasias más comunes. Se han identificado factores como las infecciones asociadas al SIDA y las infecciones no asociadas al SIDA como determinantes de la supervivencia. El tratamiento del cáncer parece mejorar la supervivencia.

Co-infection and co-localization of Kaposi sarcoma-associated herpesvirus and Epstein-Barr virus in HIV-associated Kaposi sarcoma: a case report.

Kaposi sarcoma (KS), a multifocal vascular neoplasm frequently observed in HIV-positive individuals, primarily affects the skin, mucous membranes, visceral organs, and lymph nodes. KS is associated primarily with Kaposi sarcoma-associated herpesvirus (KSHV) infection. In this case report, we present a rare occurrence of co-infection and co-localization of KSHV and Epstein-Barr virus (EBV) in KS arising from the conjunctiva, which, to our knowledge, has not been reported previously. Immunohistochemistry (IHC), DNA polymerase chain reaction (PCR), and EBV-encoded RNA in situ hybridization (EBER-ISH) were utilized to demonstrate the presence of KSHV and EBV infection in the ocular KS lesion. Nearly all KSHV-positive cells displayed co-infection with EBV. In addition, the KS lesion revealed co-localization of KSHV Latency-Associated Nuclear Antigen (LANA) and EBV Epstein Barr virus Nuclear Antigen-1 (EBNA1) by multi-colored immunofluorescence staining with different anti-EBNA1 antibodies, indicating the possibility of interactions between these two gamma herpesviruses within the same lesion. Additional study is needed to determine whether EBV co-infection in KS is a common or an opportunistic event that might contribute to KS development and progression.

Prognostic analysis of cutaneous Kaposi sarcoma based on a competing risk model.

The data regarding the prognosis of cutaneous Kaposi sarcoma (KS) was limited. The current study aimed to explore the risk factors and develop a predictive model for the prognosis of cutaneous KS patients. Data were extracted from Surveillance, Epidemiology, and End Results database from 2000 to 2018 and randomly divided into training and validation cohort. The Kaplan-Meier analysis, cumulative incidence function based on the competing risk model and Fine-Gray multivariable regression model was used to identify the prognostic factors and then construct a 5-, 10-, and 15-year KS-specific death (KSSD) nomogram for patients. The concordance index (C-index), area under the curve (AUC) of operating characteristics and calibration plots were used to evaluate the performance of the model. The clinical utility of the model was measured by decision curve analysis (DCA). In 2257 cutaneous KS patients identified from database, the overall median survival time was about 13 years. Radiotherapy (p = 0.013) and surgery (p < 0.001) could lower the KSSD, while chemotherapy (p = 0.042) and surgery (p < 0.001) could increase the overall survival (OS) of patients with metastatic and localized lesions, respectively. Race, number of lesions, surgery, extent of disease, year of diagnosis and age were identified as risk factors associated with cutaneous KS-specific survival. Performance of the nomogram was validated by calibration and discrimination, with C-index values of 0.709 and AUC for 5-, 10-, and 15-year-KSSD of 0.739, 0.728 and 0.725 respectively. DCA indicated that the nomogram had good net benefits in clinical scenarios. Using a competing-risk model, this study firstly identified the prognostic factors, and constructed a validated nomogram to provide individualized assessment and reliable prognostic prediction for cutaneous KS patients.

A retrospective study of Kaposi's sarcoma in Hotan region of Xinjiang, China.

Kaposi sarcoma (KS) is the most common cancer in patients with human immunodeficiency virus/acquired immunodeficiency syndrome (AIDS). In 1994, Chang and Moore discovered Kaposi sarcoma associated herpesvirus for the first time in KS lesions in AIDS patients. KS is a low-grade mesenchymal neoplasm of blood and lymphatic vessels that primarily affects the skin, although the disease may become disseminated to the lymphatic system, lungs, airways, or abdominal viscera. In this research, clinical characteristics and treatment of patients of Kaposi sarcoma were retrospectively analyzed in Hotan District, Xinjiang China. We look into the clinical traits, prognosis, and therapy of Kaposi sarcoma. From May 2017 to August 2022, 32 patients were treated in the People's Hospital of Hotan District, Xinjiang Uygur Autonomous Region, China. Twenty-two of these were classic Kaposi sarcomas (cKS), and 10 of these were Kaposi sarcomas linked to AIDS (AIDS-KS). The majority of KS patients were Uyghur. In terms of age at onset, AIDS-KS patients were younger than cKS patients. cKS and AIDS-KS are most frequently manifested in the feet and lower limbs. Ten patients with AIDS-KS have treated with combination antiretroviral therapy (combination antiretroviral therapy) combination chemotherapy, 5 of 10 patients had a complete response, 2 patients achieved partial response, the overall effective rate was 70%, and CD4 + T cells were greater than before. For cKS and AIDS-KS, the median overall survival was 56 and 50.8 months, respectively (P > .05). As a result, antiviral combination chemotherapy can also improve the prognosis of AIDS-KS patients.

A SEER data-based nomogram for the prognostic analysis of survival of patients with Kaposi's sarcoma.

Background: This study developed the first comprehensive nomogram for predicting the cancer-specific survival (CSS) of patients with Kaposi's sarcoma (KS). Methods: Data on the demographic and clinical characteristics of 4143 patients with KS were collected from the Surveillance, Epidemiology, and End Results (SEER) database and used for the prognostic analysis. The patients were randomly divided into two groups: training cohort (n = 2900) and validation cohort (n = 1243). Multivariate Cox regression analysis was used to identify the predictive variables for developing the first nomogram for the survival prediction of patients with KS. The new survival nomogram was further evaluated using the concordance index (C-index), area under the time-dependent receiver operating characteristic curve (AUC), net reclassification improvement (NRI), integrated discrimination improvement (IDI), calibration plotting, and decision curve analysis (DCA). Results: A nomogram was developed for determining the 3-, 5-, 8-, and 10-year CSS probabilities for patients with KS. The nomogram showed that tumor stage had the greatest influence on the CSS of patients with KS, followed by demographic variables (race, marital status, and age at diagnosis) and other clinical characteristics (surgery status, chemotherapy status, tumor risk classification, and radiotherapy status). The nomogram exhibited excellent performance based on the values of the C-index, AUC, NRI, and IDI as well as calibration plots. DCA further confirmed that the nomogram had good net benefits for 3-, 5-, 8-, and 10-year survival analyses. Conclusions: In this study, by using data from the SEER database, we developed the first comprehensive nomogram for analyzing the survival of patients with KS. This nomogram could serve as a convenient and reliable tool for clinicians to predict CSS probabilities for individual patients with KS.

Global patterns and trends in Kaposi sarcoma incidence: a population-based study.

BACKGROUND: Kaposi sarcoma is a rare, possibly angioproliferative, tumour. Kaposi sarcoma is one of the most common cancers in people living with HIV and poses a serious public health challenge in regions with high HIV burden. We aim to describe global patterns and population-wide trends in the burden of Kaposi sarcoma. METHODS: In this population-based study, the incidence and mortality estimates of Kaposi sarcoma from 185 countries and regions in 2020 were extracted from the GLOBOCAN 2020 database. The time trends in Kaposi sarcoma incidence were evaluated using the cancer registry data from Cancer Incidence in Five Continents plus from 1998 to 2012. We did not apply any inclusion or exclusion criteria to the data used in this study. Joinpoint regression was used to evaluate the average annual percentage change (AAPC) to quantify trends in the age-standardised incidence rate (ASIR) of Kaposi sarcoma. Correlation analysis was used to evaluate the relationship between the ASIR or age-standardised mortality rate (ASMR) and Human Development Index (HDI). FINDINGS: In 2020, the global estimated ASIR of Kaposi sarcoma was 0·39 (per 100 000 people), with an estimated 34 270 newly diagnosed cases (23 413 males and 10 857 females). An estimated 15 086 Kaposi sarcoma deaths were reported (9929 males and 5157 females), corresponding to an ASMR of 0·18 (per 100 000 people). In 2020, Africa accounted for 73·0% (25 010 of 34 270) of the incidence and 86·6% (13 066 of 15 086) of the deaths from Kaposi sarcoma worldwide. There was a significant correlation between the ASIR or ASMR and HDI. The incidence of Kaposi sarcoma increased in males in both Türkiye and the Netherlands. The AAPC was 11·5% (95% CI 3·2-20·4) for males in Türkiye and 2·5% (1·1-3·9) for males in the Netherlands from 1998 to 2012. The incidence of Kaposi sarcoma decreased in White Americans, Israel, Uganda, Costa Rica, Colombia, Canada, and Denmark, from 1998 to 2012. INTERPRETATION: Kaposi sarcoma is a relatively rare cancer worldwide but is endemic in some countries in southern and eastern Africa. Addressing disparities in health-care resource allocation and improving HIV/AIDS care across different HDI regions might contribute to the prevention of Kaposi sarcoma. FUNDING: The Natural Science Foundation of China Excellent Young Scientists Fund and the Natural Science Foundation of China International/Regional Research Collaboration Project. TRANSLATION: For the Chinese translation of the abstract see Supplementary Materials section.

Incident Kaposi sarcoma during the expansion of antiretroviral therapy eligibility in Nigeria: a retrospective cohort study.

INTRODUCTION: The expansion of antiretroviral therapy (ART) eligibility could lead to earlier initiation of Human Immunodeficiency Virus (HIV) treatment and consequently reduce the risk of HIV-associated Kaposi Sarcoma (KS). We investigated the impact of changes in the Nigerian HIV treatment guidelines on KS incidence among adults enrolled in HIV care in Nigeria. METHODS: We analyzed data of adults who enrolled for HIV care from January 2006 to December 2016 at one of Nigeria's largest HIV treatment centers. Based on changes in HIV treatment guidelines, we classified 2006-2009 as the pre-expansion period and 2010-2016 as the post-expansion period. We used Kaplan Meier curves to compare the incidence of KS in the pre-expansion to the post-expansion period. We used Cox regression models to assess the hazard for incident KS between the two periods after adjusting for potential confounders. RESULTS: Among 14,479 patients with HIV, the overall KS incidence was 2.35; 95% CI 2.01-2.74/1,000 person-years. The incidence of KS decreased from 2.53 to 1.58 per 1,000 person-years from 2006 to 2009 to 2010-2016. In models adjusting for age, sex, CD4-T cell count, and ART use, the risk for KS remained lower in 2010-2016 compared to 2006-2009. In analyses restricted to time on ART, there was no significant difference in KS incidence between HIV patients who enrolled in 2006-2009 and 2010-2016 after adjusting for age, sex, and CD4 T-cell count. CONCLUSION: The expansion of ART eligibility was associated with a reduced incidence of HIV-associated KS among adults initiating HIV care in Jos, Nigeria. The reduction was likely driven by earlier enrollment for HIV care and ART initiation.

Human herpesvirus-8 infection in Tunisian adult acute leukemia patients.

Background: Human herpesvirus 8 (HHV-8) has been linked to the development of Kaposi's sarcoma (KS)and multiple other hematologic malignant disorders. However, the role of HHV-8 in acute leukemia patients is unknown. Objectives: The objective of this study was to determine the prevalence of HHV-8 in Tunisian acute leukemia patients and in healthy blood donors. Methods: An indirect immunofluorescence test was used to detect the presence of anti-HHV8 antibodies. Nested PCR was used for the detection of HHV-8 DNAemia in samples of plasma. Results: The seroprevalence of HHV-8 was significantly higher in acute leukemia patients (21,4% ,15/70) than in healthy blood donors (7,1%, 5/70), (p= 0.02). Gender, type of disease, status of disease, prior blood transfusion, and outcome were not associated with HHV-8 seroprevalence. However, among acute leukemia patients, HHV-8 seroprevalence was statistically associated with older age > 40 years of age, (p=0.002). HHV-8 DNAemia was detected (1,4%) in only one patient of acute myeloid leukemia (AML) and none of the healthy blood donors. Conclusions: The seroprevalence of HHV-8 infection in Tunisian adult acute leukemia patients was three times as high compared to healthy blood donors, suggesting that patients with acute leukemia might be at increased risk of HHV-8 infection.

A prospective cohort study identifies two types of HIV+ Kaposi Sarcoma lesions: proliferative and inflammatory.

Kaposi sarcoma (KS) is the most common cancer in people living with HIV (PLWH) in many countries where KS-associated herpesvirus is endemic. Treatment has changed little in 20 years, but the disease presentation has. This prospective cohort study enrolled 122 human immunodeficiency virus (HIV) positive KS patients between 2017 and 2019 in Malawi. Participants were treated with bleomycin, vincristine and combination antiretroviral therapy, the local standard of care. One-year overall survival was 61%, and progression-free survival was 58%. The 48-week complete response rate was 35%. RNAseq (n = 78) differentiated two types of KS lesions, those with marked endothelial characteristics and those enriched in inflammatory transcripts. This suggests that different KS lesions are in different disease states consistent with the known heterogeneous clinical response to treatment. In contrast to earlier cohorts, the plasma HIV viral load of KS patients in our study was highly variable. A total of 25% of participants had no detectable HIV; all had detectable KSHV viral load. Our study affirms that many KS cases today develop in PLWH with well-controlled HIV infection and that different KS lesions have differing molecular compositions. Further studies are needed to develop predictive biomarkers for this disease.

Clinical management of Kaposi sarcoma herpesvirus-associated diseases: an update on disease manifestations and treatment strategies.

INTRODUCTION: Kaposi sarcoma herpes virus (KSHV) is associated with several diseases including Kaposi sarcoma, a form of multicentric Castleman's disease, primary effusion lymphoma, and an inflammatory cytokine syndrome. These KSHV-associated diseases (KAD) can present with heterogenous signs and symptoms that are often associated with cytokine dysregulation that may result in multiorgan dysfunction. The inability to promptly diagnose and treat these conditions can result in long-term complications and mortality. AREAS COVERED: Existing epidemiological subtypes of existing KSHV-associated diseases, specifically Kaposi sarcoma as well as the incidence of several KSHV-associated disorders are described. We review the KSHV latent and lytic phases as they correlate with KSHV-associated diseases. Given the complicated presentations, we discuss the clinical manifestations, current diagnostic criteria, existing treatment algorithms for individual KAD, and when they occur concurrently. With emerging evidence on the virus and host interactions, we evaluate novel approaches for the treatment of KAD. An extensive literature search was conducted to support these findings. EXPERT OPINION: KSHV leads to complex and concurrent disease processes that are often underdiagnosed both in the United States and worldwide. New therapies that exist for many of these conditions focus on chemotherapy-sparing options that seek to target the underlying viral pathogenesis or immunotherapy strategies.