scholarly journals KSHV/HHV8-Associated Lymphoproliferative Disorders: Lessons Learnt from People Living with HIV

Hemato ◽  
2021 ◽  
Vol 2 (4) ◽  
pp. 703-712
Author(s):  
Mark Bower ◽  
Antonino Carbone

In 1992, Kaposi sarcoma herpesvirus (KSHV/HHV8) was discovered and identified as the causative agent for Kaposi sarcoma. Subsequently, the presence of this virus has been detected in a number of lymphoproliferative disorders in people living with HIV (PLWH), including: KSHV-associated multicentric Castleman disease, primary effusion lymphoma, KSHV-positive diffuse large B-cell lymphoma, and germinotropic lymphoproliferative disorder. Each of these rare entities has subsequently been diagnosed in HIV-negative individuals. The recognition of some of these KSHV/HHV8-associated lymphoproliferative disorders has led to their inclusion in the WHO classification of lymphomas in 2008 and the revision of 2016; however, further revision is under way to update the classification. The relatively recent recognition of these lymphoproliferative disorders and their low incidence, particularly in the HIV-negative population, means that there is little published evidence and consensus on their clinical features and management. The publication of a new WHO classification of lymphomas should yield diagnostic clarity, providing an impetus for retrospective case series and prospective clinical trials in these KSHV/HHV8-associated lymphoproliferative disorders.

Author(s):  
Farizeh Aalam ◽  
Jennifer Totonchy

The incidence of Kaposi’s sarcoma-associated herpesvirus (KSHV)-associated Kaposi Sarcoma has declined precipitously in the present era of effective HIV treatment. However, KSHV-associated lymphoproliferative disorders although rare, have not seen a similar decline. Lymphoma is now a leading cause of death in people living with HIV (PLWH), indicating that the immune reconstitution provided by antiretroviral therapy is not sufficient to fully correct the lymphomagenic immune dysregulation perpetrated by HIV infection. As such, novel insights into the mechanisms of KSHV-mediated pathogenesis in the immune compartment are urgently needed in order to develop novel therapeutics aimed at prevention and treatment of KSHV-associated lymphoproliferations. In this review, we will discuss our current understanding of KSHV molecular virology in the lymphocyte compartment, concentrating on studies which explore mechanisms unique to infection in B lymphocytes.


BMJ Open ◽  
2021 ◽  
Vol 11 (1) ◽  
pp. e041734
Author(s):  
Ni Gusti Ayu Nanditha ◽  
Adrianna Paiero ◽  
Hiwot M Tafessu ◽  
Martin St-Jean ◽  
Taylor McLinden ◽  
...  

ObjectivesAs people living with HIV (PLWH) live longer, morbidity and mortality from non-AIDS comorbidities have emerged as major concerns. Our objective was to compare prevalence trends and age at diagnosis of nine chronic age-associated comorbidities between individuals living with and without HIV.Design and settingThis population-based cohort study used longitudinal cohort data from all diagnosed antiretroviral-treated PLWH and 1:4 age-sex-matched HIV-negative individuals in British Columbia, Canada.ParticipantsThe study included 8031 antiretroviral-treated PLWH and 32 124 HIV-negative controls (median age 40 years, 82% men). Eligible participants were ≥19 years old and followed for ≥1 year during 2000 to 2012.Primary and secondary outcome measuresThe presence of non-AIDS-defining cancers, diabetes, osteoarthritis, hypertension, Alzheimer’s and/or non-HIV-related dementia, cardiovascular, kidney, liver and lung diseases were identified from provincial administrative databases. Beta regression assessed annual age-sex-standardised prevalence trends and Kruskal-Wallis tests compared the age at diagnosis of comorbidities stratified by rate of healthcare encounters.ResultsAcross study period, the prevalence of all chronic age-associated comorbidities, except hypertension, were higher among PLWH compared with their community-based HIV-negative counterparts; as much as 10 times higher for liver diseases (25.3% vs 2.1%, p value<0.0001). On stratification by healthcare encounter rates, PLWH experienced most chronic age-associated significantly earlier than HIV-negative controls, as early as 21 years earlier for Alzheimer’s and/or dementia.ConclusionsPLWH experienced higher prevalence and earlier age at diagnosis of non-AIDS comorbidities than their HIV-negative controls. These results stress the need for optimised screening for comorbidities at earlier ages among PLWH, and a comprehensive HIV care model that integrates prevention and treatment of chronic age-associated conditions. Additionally, the robust methodology developed in this study, which addresses concerns on the use of administrative health data to measure prevalence and incidence, is reproducible to other settings.


Blood ◽  
2002 ◽  
Vol 100 (9) ◽  
pp. 3415-3418 ◽  
Author(s):  
Ming-Qing Du ◽  
Tim C. Diss ◽  
Hongxiang Liu ◽  
Hongtao Ye ◽  
Rifat A. Hamoudi ◽  
...  

Abstract Kaposi sarcoma–associated herpesvirus (KSHV) is known to be associated with 3 distinct lymphoproliferative disorders: primary effusion lymphoma (PEL), multicentric Castleman disease (MCD), and MCD-associated plasmablastic lymphoma. We report 3 cases of a previously undescribed KSHV-associated lymphoproliferative disorder. The disease presented as localized lymphadenopathy and showed a favorable response to chemotherapy or radiotherapy. Histologically, the lymphoproliferation is characterized by plasmablasts that preferentially involved germinal centers of the lymphoid follicles, forming confluent aggregates. They were negative for CD20, CD27, CD79a, CD138, BCL6, and CD10 but showed monotypic κ or λ light chain. Clusters of CD10+CD20+ residual follicle center cells were identified in some of the follicles. The plasmablasts were positive for both KSHV and EBV, and most of them also expressed viral interleukin-6 (vIL-6). Unexpectedly, molecular analysis of whole tissue sections or microdissected KSHV-positive aggregates demonstrated a polyclonal or oligoclonal pattern of immunoglobulin (Ig) gene rearrangement. The plasmablasts showed somatic mutation and intraclonal variation in the rearranged Ig genes, and one case expressed switched Ig heavy chain (IgA), suggesting that they originated from germinal center B cells. We propose calling this distinctive entity “KSHV-associated germinotropic lymphoproliferative disorder.”


Author(s):  
V. Logan Kennedy ◽  
Micaela Collins ◽  
Mark H. Yudin ◽  
Lena Serghides ◽  
Sharon Walmsley ◽  
...  

Data are lacking on factors that may impact conception-related decision-making among individuals living with HIV. This study’s aim was to shed light on these considerations. Participants were invited to complete a survey on preconception considerations. A rank-ordered logit model was fit to estimate the relative importance of listed consideration factors; the interaction of HIV status and the factors was assessed. Fifty-nine participants living with HIV and 18 partners (11 HIV-negative participants and 7 living with HIV) were included. Risk of vertical and horizontal HIV transmission and the effect of antiretroviral therapy on the fetus were the top considerations. However, individuals living with HIV prioritized vertical transmission, whereas HIV-negative participants prioritized horizontal transmission. Other factors of importance were probability of conception, stress of trying to conceive, cost associated with fertility clinics, and stigma associated with certain conception methods. This study builds our understanding of the preconception considerations for people living with HIV.


eLife ◽  
2021 ◽  
Vol 10 ◽  
Author(s):  
Farina Karim ◽  
Inbal Gazy ◽  
Sandile Cele ◽  
Yenzekile Zungu ◽  
Robert Krause ◽  
...  

There are conflicting reports on the effects of HIV on COVID-19. Here we analyzed disease severity and immune cell changes during and after SARS-CoV-2 infection in 236 participants from South Africa, of which 39% were people living with HIV (PLWH), during the first and second (beta dominated) infection waves. The second wave had more PLWH requiring supplemental oxygen relative to HIV negative participants. Higher disease severity was associated with low CD4 T cell counts and higher neutrophil to lymphocyte ratios (NLR). Yet, CD4 counts recovered and NLR stabilized after SARS-CoV-2 clearance in wave 2 infected PLWH, arguing for an interaction between SARS-CoV-2 and HIV infection leading to low CD4 and high NLR. The first infection wave, where severity in HIV negative and PLWH was similar, still showed some HIV modulation of SARS-CoV-2 immune responses. Therefore, HIV infection can synergize with the SARS-CoV-2 variant to change COVID-19 outcomes.


2022 ◽  
Vol 14 (1) ◽  
pp. 43-55
Author(s):  
Cristina Micali ◽  
Ylenia Russotto ◽  
Grazia Caci ◽  
Manuela Ceccarelli ◽  
Andrea Marino ◽  
...  

Hepatocellular carcinoma (HCC) accounts for approximately 75–90% of primary liver cancers and is the sixth most common cancer and the third leading cause of cancer-related deaths worldwide. In the HIV-positive population, the risk of HCC is approximately four times higher than in the general population, with higher cancer-specific mortality than in HIV-negative patients. In most cases, HCC diagnosis is made in patients younger than the HIV-negative population and in the intermediate-advanced stage, thus limiting the therapeutic possibilities. Treatment choice in HIV-positive patients with HCC is subject to cancer staging, liver function and health status, as for HIV-negative and non-HIV-negative HCC patients. There are relatively few studies on the efficacy and safety in HIV-positive patients to date in loco-regional treatments for HCC. So far, literature shows that curative treatments such as radiofrequency ablation (RFA) have no significant differences in overall survival between HIV-positive and HIV-negative patients, as opposed to palliative treatments such as TACE, where there is a significant difference in overall survival. Although it can be assumed that the most recently discovered loco-regional therapies are applicable to HIV-positive patients with HCC in the same way as HIV-negative patients, further studies are needed to confirm this hypothesis. The purpose of our review is to evaluate these treatments, their efficacy, effectiveness, safety and their applicability to HIV-positive patients.


Cancers ◽  
2021 ◽  
Vol 13 (17) ◽  
pp. 4366
Author(s):  
Jose-Tomas Navarro ◽  
José Moltó ◽  
Gustavo Tapia ◽  
Josep-Maria Ribera

Despite widespread use of combined antiretroviral therapy (cART) and increased life expectancy in people living with HIV (PLWH), HIV-related lymphomas (HRL) remain a leading cause of cancer morbidity and mortality for PLWH, even in patients optimally treated with cART. While the incidence of aggressive forms of non-Hodgkin lymphoma decreased after the advent of cART, incidence of Hodgkin lymphoma (HL) has increased among PLWH in recent decades. The coinfection of Epstein–Barr virus plays a crucial role in the pathogenesis of HL in the HIV setting. Currently, PLWH with HRL, including HL, are treated similarly to HIV-negative patients and, importantly, the prognosis of HL in PLWH is approaching that of the general population. In this regard, effective cART during chemotherapy is strongly recommended since it has been shown to improve survival rates in all lymphoma subtypes, including HL. As a consequence, interdisciplinary collaboration between HIV specialists and hemato-oncologists for the management of potential drug–drug interactions and overlapping toxicities between antiretroviral and antineoplastic drugs is crucial for the optimal treatment of PLWH with HL. In this article the authors review and update the epidemiological, clinical and biological aspects of HL presenting in PLWH with special emphasis on advances in prognosis and the factors that have contributed to it.


PLoS ONE ◽  
2021 ◽  
Vol 16 (1) ◽  
pp. e0245743
Author(s):  
Sorelle Mekachie Sandie ◽  
Irene Ule Ngole Sumbele ◽  
Martin Mih Tasah ◽  
Helen Kuokuo Kimbi

Background Both malaria and intestinal parasites are endemic in Cameroon, and their co-infection can be of great impact on anaemia among people living with HIV (PLWH). This community-based retrospective cohort study determined the prevalence and association of infections with anaemia in PLWH and HIV-negative individuals in Buea, Cameroon from March to August 2019. Methods The study population comprised of 190 PLWH and 216 consenting HIV-negative individuals from the Buea community. Participants were examined clinically, the collected blood sample was used for malaria parasite (MP) detection, HIV diagnosis and haemoglobin (Hb) measurement while stool samples were examined for the detection of intestinal parasites (IPs). Proportions were compared using Pearson’s Chi-square test and association of anaemia with independent variables was evaluated using logistic regression analysis. Results Out of the 406 participants, MP, IPs and MP/IP co-infection prevalences were 15.5%, 13.0% and 3.0% respectively. PLWH had a higher prevalence of MP (16.3%, P = 0.17), IPs (23.7%, P ˂ 0.001) and MP/IPs co-infection (3.7%, P = 0.04) when compared with HIV-negative participants. Similarly, PLWH had significantly lower mean haemoglobin value (11.10 ± 1.54 g/dL) than their HIV-negative counterparts (12.45 ± 2.06 g/dL). Also, PLWH co-infected with MP and IPs were observed to have a significantly lower mean haemoglobin value (10.6 ± 1.21 g/dL). PLWH had a significantly (P ˂ 0.001) higher prevalence of mild (56.8%), moderate (18.4%) and severe (1.6%) anaemia when compared with HIV-negative counterparts. The significant risk factors associated with anaemia included being febrile (P = 0.03), MP-infected only (P = 0.001), HIV-infected only (P < 0.001), having dual (P < 0.001) or triple-infections (P = 0.03). Conclusion Malaria and intestinal parasites remain public health concerns among PLWH and anaemia as a serious haematological abnormality gets exacerbated even with the viral load suppression. Hence, routine medical check-ups among PLWH are recommended.


2021 ◽  
Vol 33 (1) ◽  
pp. 1-15
Author(s):  
Marcie Berman ◽  
Lisa A. Eaton ◽  
Ryan J. Watson ◽  
Jessica L. Maksut ◽  
Katherine B. Rucinski ◽  
...  

HIV discrimination has served as a barrier to addressing the HIV epidemic and providing effective HIV treatment and care. Measuring HIV discrimination, particularly covert HIV discrimination, has proven to be complex. Adapted from a previous scale, we developed a perpetuated HIV micro-aggressions scale to assess covert forms of discriminatory beliefs among HIV-negative/unknown HIV status individuals. Factor analysis resulted in three subscales, explaining 73.58% of the scale's variance. The new scale demonstrated both convergent validity (HIV prejudice, HIV stereotypes) and discriminant validity (alcohol use, depressive symptomology). Perpetuated HIV microaggressions were significantly associated with HIV conspiracy beliefs, HIV prejudice, and HIV stereotypes. This new scale can serve as an important tool in evaluating perpetuated HIV microaggressions among HIV-negative individuals.


AIDS ◽  
2019 ◽  
Vol 33 (2) ◽  
pp. 259-268 ◽  
Author(s):  
Davide De Francesco ◽  
Ferdinand W. Wit ◽  
Alexander Bürkle ◽  
Sebastian Oehlke ◽  
Neeltje A. Kootstra ◽  
...  

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