scholarly journals Molecular Virology of KSHV in the Lymphocyte Compartment—Insights From Patient Samples and De Novo Infection Models

2020 ◽  
Vol 10 ◽  
Author(s):  
Farizeh Aalam ◽  
Jennifer Totonchy
Keyword(s):  
B Lymphocytes ◽  
De Novo ◽  
Kaposi Sarcoma ◽  
Immune Dysregulation ◽  
Hiv Treatment ◽  
Lymphoproliferative Disorders ◽  
People Living With Hiv ◽  
Molecular Virology ◽  
Infection Models ◽  
Living With Hiv

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.

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
Keyword(s):  
Who Classification ◽  
Primary Effusion Lymphoma ◽  
Case Series ◽  
Kaposi Sarcoma ◽  
B Cell Lymphoma ◽  
Lymphoproliferative Disorders ◽  
People Living With Hiv ◽  
Living With Hiv ◽  
Hiv Negative

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.

scholarly journals Analysis of KSHV B lymphocyte lineage tropism in human tonsil reveals efficient infection of CD138+ plasma cells

2020 ◽  
Author(s):  
Farizeh Aalam ◽  
Romina Nabiee ◽  
Jesus Ramirez Castano ◽  
Jennifer E. Totonchy
Keyword(s):  
B Lymphocytes ◽  
B Lymphocyte ◽  
Plasma Cells ◽  
De Novo ◽  
Ex Vivo ◽  
Kaposi Sarcoma ◽  
Human Tonsil ◽  
Kshv Infection ◽  
Molecular Virology

AbstractDespite 25 years of research, the basic virology of Kaposi Sarcoma Herpesviruses (KSHV) in B lymphocytes remains poorly understood. This study seeks to fill critical gaps in our understanding by characterizing the B lymphocyte lineage-specific tropism of KSHV. Here, we use lymphocytes derived from 40 human tonsil specimens to determine the B lymphocyte lineages targeted by KSHV early during de novo infection in our ex vivo model system. We characterize the immunological diversity of our tonsil specimens and determine that overall susceptibility of tonsil lymphocytes to KSHV infection varies substantially between donors. We demonstrate that a variety of B lymphocyte subtypes are susceptible to KSHV infection and identify CD138+ plasma cells as a rare, but highly targeted cell type for de novo KSHV infection. Finally, we determine that the host immunological status influences the course of de novo infection in B lymphocytes. These results improve our understanding of KSHV transmission and the biology of early KSHV infection in a naïve human host, and lay a foundation for further characterization of KSHV molecular virology in B lymphocyte lineages.

The Bio/Necropolitics of ACTG 076: Lessons from Pregnant Women of Colour Living with HIV for Treatment for Prevention in the Twenty-first Century

Somatechnics ◽  
2020 ◽  
Vol 10 (2) ◽  
pp. 233-253
Author(s):  
Eli Manning
Keyword(s):  
Hiv Transmission ◽  
Ethical Dilemmas ◽  
Hiv Treatment ◽  
First Century ◽  
Hiv Positive ◽  
Treatment As Prevention ◽  
People Living With Hiv ◽  
Hiv Positive Women ◽  
Aids Clinical Trials ◽  
Living With Hiv

Since the pharmaceutical turn, using HIV treatment to prevent transmission is increasingly common. Treatment as Prevention®, or TasP, has relied on HIV treatment to prevent HIV transmission, targeting people living with HIV. However, TasP is predicated on troublesome heterosexist, classist, and racist medical practices borrowed from various times and spaces that enact biopolitical and necropolitical relations. This paper discusses the debate surrounding the first clinical trial that used HIV treatment to prevent transmission from woman-to-foetus. The 1994 landmark AIDS Clinical Trials Group 076 study laid the groundwork for using HIV treatment to prevent HIV transmission, the essential precursor to TasP. By examining the concerns of HIV positive women of colour and other AIDS activists, we are able to understand the ethical dilemmas and practical consequences that still haunt today's game-changing uses of HIV treatment for prevention and to see how biopolitics and necropolitics persist in TasP.

scholarly journals Influence of Material Deprivation on Clinical Outcomes Among People Living with HIV in High-Income Countries: A Systematic Review and Meta-analysis

2021 ◽  
Author(s):  
Vasiliki Papageorgiou ◽  
Bethan Davies ◽  
Emily Cooper ◽  
Ariana Singer ◽  
Helen Ward
Keyword(s):  
Systematic Review ◽  
Social Determinants ◽  
Meta Analysis ◽  
Hiv Treatment ◽  
Material Deprivation ◽  
Hiv Care ◽  
People Living With Hiv ◽  
Hiv Care Continuum ◽  
Care Continuum ◽  
Living With Hiv

AbstractDespite developments in HIV treatment and care, disparities persist with some not fully benefiting from improvements in the HIV care continuum. We conducted a systematic review to explore associations between social determinants and HIV treatment outcomes (viral suppression and treatment adherence) in high-income countries. A random effects meta-analysis was performed where there were consistent measurements of exposures. We identified 83 observational studies eligible for inclusion. Social determinants linked to material deprivation were identified as education, employment, food security, housing, income, poverty/deprivation, socioeconomic status/position, and social class; however, their measurement and definition varied across studies. Our review suggests a social gradient of health persists in the HIV care continuum; people living with HIV who reported material deprivation were less likely to be virologically suppressed or adherent to antiretrovirals. Future research should use an ecosocial approach to explore these interactions across the lifecourse to help propose a causal pathway.

A model to predict adherence to antiretroviral therapy among people living with HIV

2021 ◽  
pp. sextrans-2021-055222
Author(s):  
Hui Chen ◽  
Rusi Long ◽  
Tian Hu ◽  
Yaqi Chen ◽  
Rongxi Wang ◽  
...  
Keyword(s):  
Antiretroviral Therapy ◽  
Hiv Treatment ◽  
Poor Adherence ◽  
People Living With Hiv ◽  
Art Adherence ◽  
Snowball Sampling ◽  
Hiv Viral Load ◽  
Temporal Validation ◽  
Suboptimal Adherence ◽  
Living With Hiv

ObjectivesSuboptimal adherence to antiretroviral therapy (ART) dramatically hampers the achievement of the UNAIDS HIV treatment targets. This study aimed to develop a theory-informed predictive model for ART adherence based on data from Chinese.MethodsA cross-sectional study was conducted in Shenzhen, China, in December 2020. Participants were recruited through snowball sampling, completing a survey that included sociodemographic characteristics, HIV clinical information, Information-Motivation-Behavioural Skills (IMB) constructs and adherence to ART. CD4 counts and HIV viral load were extracted from medical records. A model to predict ART adherence was developed from a multivariable logistic regression with significant predictors selected by Least Absolute Shrinkage and Selection Operator (LASSO) regression. To evaluate the performance of the model, we tested the discriminatory capacity using the concordance index (C-index) and calibration accuracy using the Hosmer and Lemeshow test.ResultsThe average age of the 651 people living with HIV (PLHIV) in the training group was 34.1±8.4 years, with 20.1% reporting suboptimal adherence. The mean age of the 276 PLHIV in the validation group was 33.9±8.2 years, and the prevalence of poor adherence was 22.1%. The suboptimal adherence model incorporates five predictors: education level, alcohol use, side effects, objective abilities and self-efficacy. Constructed by those predictors, the model showed a C-index of 0.739 (95% CI 0.703 to 0.772) in internal validation, which was confirmed be 0.717 via bootstrapping validation and remained modest in temporal validation (C-index 0.676). The calibration capacity was acceptable both in the training and in the validation groups (p>0.05).ConclusionsOur model accurately estimates ART adherence behaviours. The prediction tool can help identify individuals at greater risk for poor adherence and guide tailored interventions to optimise adherence.

Perpetuated HIV Microaggressions: A Novel Scale to Measure Subtle Discrimination Against People Living With HIV

2021 ◽  
Vol 33 (1) ◽  
pp. 1-15
Author(s):  
Marcie Berman ◽  
Lisa A. Eaton ◽  
Ryan J. Watson ◽  
Jessica L. Maksut ◽  
Katherine B. Rucinski ◽  
...  
Keyword(s):  
Convergent Validity ◽  
Discriminant Validity ◽  
Hiv Treatment ◽  
People Living With Hiv ◽  
Depressive Symptomology ◽  
Subtle Discrimination ◽  
Conspiracy Beliefs ◽  
Living With Hiv ◽  
Hiv Negative ◽  
Hiv Discrimination

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.

Factors associated with interest in a long-acting HIV regimen: perspectives of people living with HIV and healthcare providers in four European countries

2021 ◽  
pp. sextrans-2020-054648
Author(s):  
Babatunde Akinwunmi ◽  
Daniel Buchenberger ◽  
Jenny Scherzer ◽  
Martina Bode ◽  
Paolo Rizzini ◽  
...  
Keyword(s):  
Unmet Needs ◽  
Resource Constraints ◽  
Hiv Treatment ◽  
Transmission Risk ◽  
People Living With Hiv ◽  
Privacy Concerns ◽  
Medical Needs ◽  
Suboptimal Adherence ◽  
Long Acting ◽  
Living With Hiv

ObjectivesA novel long-acting regimen (LAR) of cabotegravir and rilpivirine for HIV treatment requires dosing every 2 months instead of daily. We assessed what proportion of people living with HIV and physicians would be interested in trying and offering LAR respectively and why.Methods688 people living with HIV on treatment, and 120 HIV physicians completed web-based surveys in Germany, Italy, the UK and France during 2019. Balanced description of a hypothetical LAR regarding efficacy, administration and possible side effects were provided. The hypothetical long-acting injections were assumed to be cost-neutral to current daily oral antiretrovirals. Interest of people living with HIV in trying (‘very’/’highly’) and physicians’ willingness to offer (‘definitely’/’probably’) this LAR in different situations, with perceived benefits/concerns was measured.ResultsOf people living with HIV, 65.8% were interested in trying LAR. The majority (~80%–90%) of those with unmet needs felt LAR would help, including those with strong medical needs (malabsorption and interfering gastrointestinal conditions), suboptimal adherence, confidentiality/privacy concerns and emotional burden of daily dosing. Of physicians, percentage willing to offer LAR varied situationally: strong medical need (dysphagia, 93.3%; malabsorption, 91.6%; interfering gastrointestinal issues, 90.0%; central nervous system disorders, 87.5%); suboptimal adherence (84.2%); confidentiality/privacy concerns (hiding medications, 86.6%) and convenience/lifestyle (84.2%). People living with HIV liked LAR for not having to carry pills when travelling (56.3%); physicians liked the increased patient contact (54.2%). Furthermore, 50.0% of people living with HIV perceived LAR would minimise transmission risk and improve their sexual health. The most disliked attribute was scheduling appointments (37.2%) and resource constraints (57.5%) for people living with HIV and physicians, respectively. Physicians estimated 25.7% of their patients would actually switch.ConclusionProviders and people living with HIV viewed the described LAR as addressing several unmet needs. Alternative treatment routes and especially LAR may improve adherence and quality of life.

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