HIV-associated Malignancies Research Articles

Hemophagocytic Lymphohistiocytosis as an Unusual Presentation in a Patient with Human Immunodeficiency Virus-associated Bone Marrow Classic Hodgkin Lymphoma: A Case Report with Literature Review

Abstract Introduction/Objective Compared to the general population, people living with human immunodeficiency virus (HIV) have a higher incidence of lymphoproliferative disorders including classic Hodgkin lymphoma (CHL). Hemophagocytic lymphohistiocytosis (HLH) triggers in HIV patients include HIV itself and HIV-associated malignancies or infections, all of which can have many overlapping symptoms, causing diagnostic challenges and delays in initiating treatments. Methods/Case Report A 56-year-old HIV-positive man presented with septic shock-like symptoms, pancytopenia, hyperferritinemia, transaminitis, elevated IL2-receptor alpha and hepatomegaly. Mild retroperitoneal lymphadenopathy found on imaging yielded non-diagnostic biopsies. A bone marrow (BM) biopsy showed no malignancy or disseminated infections and a rare hemophagocyte. Treatment for HIV-triggered HLH lead to a marked clinical improvement. Three months later he presented with worsening symptoms, negative cultures, and an EBV+ CHL on a BM biopsy. Mild increase in lymphadenopathy and multiple liver/spleen hypodensities found on imaging could not be biopsied due to rapidly deteriorating patient’s condition and death. Results (if a Case Study enter NA) NA Conclusion Per studies, HLH is more frequent in the HIV-associated lymphomas compared to the non-HIV- associated ones, usually presenting as a sepsis-like syndrome in these patients. Probability of HLH development was particularly high with BM involvement and CHL. From 2010, seven cases of HIV-associated CHL presenting with HLH were found in the literature with these findings: (n=8, including ours) sex- all males; average age- 45 years (range 28- 64); average HIV viral loads- 83,369 copies/mL (range: undetectable->300,000); average absolute CD4 count- 98 cells/microliter (range: 8-314); interval from HIV diagnosis- new to 26 years; anti-retroviral treatment- 6; symptoms- fever (all), other symptoms were variable; HLH-2004 protocol criteria- all; biopsy-proven hemophagocytes- 3; EBV+ CHL- all (6 were diagnosed on BM biopsies); outcomes- remission (2), response to treatment (4), death (2). CHL- triggered HLH in HIV patients is a complex diagnostic entity. A high index of suspicion and thorough investigations including early BM biopsies can ensure better outcomes.

Impact of a multicomponent navigation strategy on stigma among people living with HIV and Kaposi's sarcoma in Kenya: a qualitative analysis.

Persons with HIV-associated Kaposi's sarcoma (KS) experience three co-existing stigmatizing health conditions: skin disease, HIV, and cancer, which contribute to a complex experience of stigmatization and to delays in diagnosis and treatment. Despite the importance of stigma among these patients, there are few proven stigma-reduction strategies for HIV-associated malignancies. Using qualitative methods, we explore how people with HIV-associated KS in western Kenya between August 2022 and 2023 describe changes in their stigma experience after participation in a multicomponent navigation strategy, which included 1) physical navigation and care coordination, 2) video-based education with motivational survivor stories, 3) travel stipend, 4) health insurance enrollment assistance, 5) health insurance stipend, and 6) peer mentorship. A purposive sample of persons at different stages of chemotherapy treatment were invited to participate. Participants described how a multicomponent navigation strategy contributed to increased knowledge and awareness, a sense of belonging, hope to survive, encouragement, and social support, which served as stigma mitigators, likely counteracting the major drivers of intersectional stigma in HIV-associated KS.

Disparities in cancer care: Is there a benefit for increased use of inpatient chemotherapy (IPC) in safety-net hospitals?

e13690 Background: Safety net hospitals provide care to a large number of vulnerable patients (pts) regardless of their ability to pay (1). These pts often have barriers to acceptance at many hospitals, including lack of or poor insurance, social and economic challenges. Additionally, pts frequently present with more advanced disease (2). Systemic treatment is preferentially administered on an ambulatory basis given several factors: clear financial incentives; effective supportive care; the association of good performance status (PS) with better outcomes; and patient preference (3). Only a few malignancies require inpatient systemic treatment. Strong social support is required for safe and effective ambulatory care, thus especially challenging pts at safety net hospitals in which social constraints are common. Methods: We reviewed patterns of IPC to determine efficacy and outcomes over a 3-year period at a safety net hospital, examining: malignancy type, reason for IPC treatment, treatment regimen (typically outpatient or inpatient), length of stay, and survival. Results: 82 pts met criteria. 56% had hematologic or HIV-associated malignancies. Solid tumor types included GI, breast, GYN, GU and small cell malignancies. Reasons for IPC were progression, worsening symptoms, declining PS in 55% and social constraints in 11%. Patient death within 3 months of IPC, or direct discharge to hospice/nursing home occurred in 42%. Further outpatient chemotherapy was never given in 50%. Death occurred in 15% of pts on the same hospitalization as the IPC; several additional pts were readmitted and died within one month. Individuals receiving IPC due to poor social support frequently required rapid rehospitalization, had poor outpatient follow-up, or died shortly thereafter. Three month survival was more favorable in pts with multiple myeloma or those admitted for drug-desensitization. Conclusions: Outcomes, including survival and rapid rehospitalization, were poor for pts receiving typical outpatient regimens on an inpatient basis whether due to social constraints, declining PS or worsening symptoms. A large percentage of pts never received further chemotherapy. IPC is costly, undesired by pts, and is often not a good use of resources. Pts with highly responsive cancers with fair to good PS had acceptable outcomes. IPC should be reserved for such pts if alternative outpatient regimens are not available. Earlier discussion of hospice and goals should not be replaced by chemotherapy. Institutional unavailability of key oral agents and limited outpatient resources often contribute to IPC. Better access to modern agents, enhanced social support, enlarged and better supported outpatient resources, as well as improved decision making improve cancer care. Our results do not support IPC as a frequent approach to cancer care in safety net hospitals. 1. Popescu, JAMA 2019. 2. Farkas, JCO 2012. 3. Mor, J Clin Epid 1988.

Malignancies in individuals living with HIV/AIDS

Background. The incidence of malignancy is heightened in individuals infected with Human Immunodeficiency Virus (HIV). Despite a decrease in the incidence of HIV infection resulting from antiretroviral therapy (ART), the prevalence of HIV-associated malignancies remains substantial. Objective. Our objective was to examine the types of cancer that initially manifest in individuals infected with HIV or emerge during their subsequent observation period. Material and method. The study conducted a retrospective analysis of demographic characteristics, malignancy types, presenting symptoms, mode of transmission, HIV-RNA levels, and CD4/CD8 ratios in individuals living with HIV who developed malignancies and were under follow-up at the Infectious Diseases Polyclinic between October 2018 and December 2022. Results. Out of the 465 patients who were monitored during the study, 27 individuals (5.8%) were diagnosed with various malignancies. Among these patients, 22 (81%) were men and 5 (19%) were women. The average age of the patients ranged from 45.87 to 9.12 years. Among the patients, 17 (63%) were married and 10 (17%) were single. In terms of education, 16 patients (59.3%) had completed primary school, 7 patients (25.9%) were university graduates, and 4 patients (14.8%) had completed high school. The mode of HIV transmission in all patients was through sexual intercourse. The reasons for testing varied, with 8 patients (29.7%) being tested due to fever, 6 patients (22.2%) before undergoing surgery, 3 patients (11.1%) due to weight loss, and 2 patients (7.4%) tested for reasons such as job application, diarrhea, pre-blood donation, lymphadenomegaly, and dysphagia. The most common types of malignancies observed in the patients were non-Hodgkin’s lymphoma (NHL) with 11 cases (40.7%), followed by Kaposi’s sarcoma (KS) with 5 cases (18.5%), and cervical carcinoma with 3 cases (11.1%). Conclusion. The incidence of cancer is higher among individuals with HIV. There is a need to enhance the awareness among both healthcare providers who specialize in HIV care and those who do not.

HIV associated malignancies presenting as acute pancreatitis: a case series.

Acute pancreatitis (AP) may be the presenting symptom in a small percentage of patients harbouring pancreatic or extra pancreatic tumours. This case series aims to describe the pathological spectrum of tumours detected in two AP cohorts from a high HIV-endemic region. Prospectively collected databases of patients admitted with AP over two periods 2001 to 2010 and 2013 to 2015, were retrospectively evaluated to detect those with pancreatic and extra-pancreatic tumours. The diagnosis of AP was by standard criteria. HIV infection and CD4 counts were routinely tested for in the latter period and only tested on clinical grounds in the initial period. CT scan was performed when there was diagnostic doubt, predicted severe disease, and failure to improve clinically after one week. Demographic, clinical, investigative, and pathology details were collected and presented. HIV-positive patients admitted with AP were 106 (17%) of 628 in the first period and 90 (38%) of 238 of the second period. No tumours were diagnosed in the HIV-negative patients. Seven of the HIV-positive patients had tumours diagnosed at endoscopy, CT scan, and endoscopic retrograde cholangiography. Of the seven HIV-positive patients with tumours, two patients had a CD4 count above 200. There were four patients with lymphoma involving the pancreatic head, three having associated cholestasis, and three patients with Kaposi's Sarcoma. One Kaposi's sarcoma patient died three months after presentation. One patient with lymphoma died on day 14 and another two months after initial presentation, and the remaining four patients were referred to oncology. Despite their rarity (< 4%), when HIV-positive patients with low CD4 count and cholestasis present with AP,tumours should be suspected and evaluated by cross sectional imaging and endoscopic ultrasound.

POSTER: ABCL-189 The Spectrum of HIV-Associated Hematological Malignancies at a Tertiary Care Centre in North India

POSTER: ABCL-189 The Spectrum of HIV-Associated Hematological Malignancies at a Tertiary Care Centre in North India

ABCL-189 The Spectrum of HIV-Associated Hematological Malignancies at a Tertiary Care Centre in North India

ABCL-189 The Spectrum of HIV-Associated Hematological Malignancies at a Tertiary Care Centre in North India

Oncogenic Proteomics Approaches for Translational Research and HIV-Associated Malignancy Mechanisms.

Recent advances in the field of proteomics have allowed extensive insights into the molecular regulations of the cell proteome. Specifically, this allows researchers to dissect a multitude of signaling arrays while targeting for the discovery of novel protein signatures. These approaches based on data mining are becoming increasingly powerful for identifying both potential disease mechanisms as well as indicators for disease progression and overall survival predictive and prognostic molecular markers for cancer. Furthermore, mass spectrometry (MS) integrations satisfy the ongoing demand for in-depth biomarker validation. For the purpose of this review, we will highlight the current developments based on MS sensitivity, to place quantitative proteomics into clinical settings and provide a perspective to integrate proteomics data for future applications in cancer precision medicine. We will also discuss malignancies associated with oncogenic viruses such as Acquire Immunodeficiency Syndrome (AIDS) and suggest novel mechanisms behind this phenomenon. Human Immunodeficiency Virus type-1 (HIV-1) proteins are known to be oncogenic per se, to induce oxidative and endoplasmic reticulum stresses, and to be released from the infected or expressing cells. HIV-1 proteins can act alone or in collaboration with other known oncoproteins, which cause the bulk of malignancies in people living with HIV-1 on ART.

Abstract 6762: Tumor immune microenvironment &amp;genomic features of non-small cell lung carcinomas in patients with HIV (PWH)

Abstract Introduction: Lung cancer is the leading cause of cancer-related death among PWH with a relative risk that is over 3-fold higher compared to the uninfected population. In addition, HIV-infected patients with non-small cell lung cancer (NSCLC) have a significantly worse prognosis. The determinants for these associations remain uncertain. Methods: We investigated the immune contexture of 18 primary NSCLCs from PWH and 19 clinicopathologically matched NSCLCs from HIV-negative cases represented in tissue microarrays using 37-plex Imaging Mass Cytometry (IMC) panels including cell phenotype markers (CK,CD4,CD8,CD20,CD45RO,CD25,etc), immunomodulatory targets (PD-L1,PD-L2,B7-H3,B7-H4,B2M,etc) and DNA damage response/repair (DDR) indicators (γH2AX, RAD51,BRCA1,53BP1,etc). The samples were analyzed using single-cell tissue segmentation and spatial analysis. A subset of cases was also studied using whole exome DNA sequencing (WES) and mRNA sequencing (RNAseq). Results: NSCLCs from PWH showed comparable levels of tumor infiltrating lymphocytes (TILs) relative to HIV-negative cases with a trend towards a lower CD4+/CD8+ cell ratio. However, CD4+ and CD8+ TILs in PWH showed higher levels of markers associated with T-cell activation and dysfunction including GZB, CD25, Ki-67, PD-1, LAG-3, and TIM-3 than non-HIV tumors. The epithelial tumor cells in HIV-associated cases showed higher levels of the immunomodulatory ligands PD-L1, CD47, B7-H4 and VISTA; and altered levels of the DDR markers γH2AX, BRCA1 and 53BP1 relative to the non-HIV controls. Differences were also seen in tumor-associated macrophages consistent with an immune regulatory environment. The spatial analysis of tumor and immune cells revealed a distinct topographic distribution of these cells in HIV-associated malignancies. WES analysis showed a higher nonsynonymous tumor mutational burden in HIV-associated tumors (400 vs 202 mean mutations/exome) with increased predicted HLA class-I neoantigens and a numerically higher immunoediting score than the non-HIV group. Exploratory analysis identified enrichment in RYR2 and KIAA1671 gene mutations in HIV-associated malignancies. RNAseq revealed distinct mRNA expression profiles of HIV-positive and negative NSCLCs with a fraction of transcripts showing differential expression associated with tumor suppressor functions, interleukin signaling and DDR. Conclusion: NSCLCs in PWH display profound immunological and genomic alterations suggesting defective immunosurveillance. Our study reveals novel characteristics of HIV-associated NSCLC with possible clinical implications for this growing and understudied population. Citation Format: Shruti Desai, Kishu Ranjan, Syim Salahuddin, Ramsey Yusuf, Jianlei Gu, Daiwei Tang, Yong Kong, Barani Kumar Rajendran, Hongyu Zhao, Yuval Kluger, Sarah Goldberg, Brinda Emu, Kurt Alex Schalper. Tumor immune microenvironment &amp;genomic features of non-small cell lung carcinomas in patients with HIV (PWH) [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 6762.

Abstract PL02-04: Malignancies in People with HIV: Successes and Challenges at the Intersection of Virology, Immunology, and Oncology

Abstract PL02-04: Malignancies in People with HIV: Successes and Challenges at the Intersection of Virology, Immunology, and Oncology

Genomic changes in Kaposi Sarcoma-associated Herpesvirus and their clinical correlates.

Kaposi sarcoma (KS), a common HIV-associated malignancy, presents a range of clinicopathological features. Kaposi sarcoma-associated herpesvirus (KSHV) is its etiologic agent, but the contribution of viral genomic variation to KS development is poorly understood. To identify potentially influential viral polymorphisms, we characterized KSHV genetic variation in 67 tumors from 1-4 distinct sites from 29 adults with advanced KS in Kampala, Uganda. Whole KSHV genomes were sequenced from 20 tumors with the highest viral load, whereas only polymorphic genes were screened by PCR and sequenced from 47 other tumors. Nine individuals harbored ≥1 tumors with a median 6-fold over-coverage of a region centering on K5 and K6 genes. K8.1 gene was inactivated in 8 individuals, while 5 had mutations in the miR-K10 microRNA coding sequence. Recurring inter-host polymorphisms were detected in K4.2 and K11.2. The K5-K6 region rearrangement breakpoints and K8.1 mutations were all unique, indicating that they arise frequently de novo. Rearrangement breakpoints were associated with potential G-quadruplex and Z-DNA forming sequences. Exploratory evaluations of viral mutations with clinical and tumor traits were conducted by logistic regression without multiple test corrections. K5-K6 over-coverage and K8.1 inactivation were tentatively correlated (p<0.001 and p = 0.005, respectively) with nodular rather than macular tumors, and with individuals that had lesions in ≤4 anatomic areas (both p≤0.01). Additionally, a trend was noted for miR-K10 point mutations and lower survival rates (HR = 4.11, p = 0.053). Two instances were found of distinct tumors within an individual sharing the same viral mutation, suggesting metastases or transmission of the aberrant viruses within the host. To summarize, KSHV genomes in tumors frequently have over-representation of the K5-K6 region, as well as K8.1 and miR-K10 mutations, and each might be associated with clinical phenotypes. Studying their possible effects may be useful for understanding KS tumorigenesis and disease progression.

Abdominopelvic CT Imaging Findings in the Emergency Department in Patients With HIV Positive Status: Single Institute Experience

ObjectiveTo assess emergency department (ED) abdominopelvic computed tomography (CT) imaging utilization and findings in patients with known human immunodeficiency virus (HIV) positive status. Materials and MethodsA retrospective chart review of imaging, clinical, and laboratory data was performed for HIV positive patients who demonstrated HIV-related findings on abdominopelvic CT imaging performed within the ED. ResultsOne hundred and eighty-eight patients with 522 CT scans of the abdomen and/or pelvis were reviewed. 47 patients with HIV presenting to the ED on 82 separate occasions were included in this study (mean age 43.3 years). Patients presented to the ED with infectious/inflammatory disease (n = 54) or history of HIV-related malignancy or new/worsening HIV-related malignancy (n = 28). The most common findings on abdominopelvic CT were anorectal pathology including anorectal abscess or proctitis (n = 22), followed by colitis (n = 19). Findings of HIV-associated malignancy were less common, including anal/rectal cancer (n = 7), Kaposi's sarcoma (n = 4), and lymphoma (n = 2). At the time of ED visit, 25.6% (n = 21) of patients had acquired immunodeficiency syndrome (AIDS). Higher WBC counts were found in the infectious/inflammatory group (P = 0.021) and patients without AIDS (P = 0.0159), while lower WBC counts were associated with new or worsening malignancy (P = 0.007) and AIDS (P = 0.0000). Patients with AIDS were more likely to be deceased at the time of our study. ConclusionsThe majority of ED visits within our population were attributed to infectious/inflammatory etiologies. CT findings demonstrated predominantly infectious/inflammatory processes, with anorectal pathology being the most common. Findings of malignancy on CT were less common, while opportunistic infections and AIDS-defining malignancies were uncommon.

Barriers and facilitators to chemotherapy initiation and adherence for patients with HIV-associated Kaposi’s sarcoma in Kenya: a qualitative study

BackgroundKaposi sarcoma is one of the most prevalent HIV-associated malignancies in sub-Saharan Africa and is often diagnosed at advanced stage of disease. Only 50% of KS patients who qualify for chemotherapy receive it and adherence is sub-optimal.Methods57 patients > 18 years with newly diagnosed KS within the AMPATH clinic network in Western Kenya were purposively selected to participate in semi-structured interviews stratified by whether they had completed, partially completed, or not completed chemotherapy for advanced stage KS. We based the interview guide and coding framework on the situated Information, Motivation, Behavioral Skills (sIMB) framework, in which the core patient centered IMB constructs are situated into the socioecological context of receiving care.ResultsOf the 57 participants, the median age was 37 (IQR 32–41) and the majority were male (68%). Notable barriers to chemotherapy initiation and adherence included lack of financial means, difficulty with convenience of appointments such as distance to facility, appointment times, long lines, limited appointments, intrapersonal barriers such as fear or hopelessness, and lack of proper or sufficient information about chemotherapy. Factors that facilitated chemotherapy initiation and adherence included health literacy, motivation to treat symptoms, improvement on chemotherapy, prioritization of self-care, resilience while experiencing side effects, ability to carry out behavioral skills, obtaining national health insurance, and free chemotherapy.ConclusionOur findings about the barriers and facilitators to chemotherapy initiation and adherence for KS in Western Kenya support further work that promotes public health campaigns with reliable cancer and chemotherapy information, improves education about the chemotherapy process and side effects, increases oncology service ability, supports enrollment in national health insurance, and increases incorporation of chronic disease care into existing HIV treatment networks.

A type III effectiveness-implementation hybrid evaluation of a multicomponent patient navigation strategy for advanced-stage Kaposi’s sarcoma: protocol

BackgroundFor people with advanced-stage Kaposi’s sarcoma (KS), a common HIV-associated malignancy in sub-Saharan Africa, mortality is estimated to be 45% within 2 years after KS diagnosis, despite increasingly wide-spread availability of antiretroviral therapy and chemotherapy. For advanced-stage KS, chemotherapy in addition to antiretroviral therapy improves outcomes and saves lives, but currently, only ~50% of people with KS in western Kenya who have an indication for chemotherapy actually receive it. This protocol describes the evaluation of a multicomponent patient navigation strategy that addresses common barriers to service penetration of and fidelity to evidence-based chemotherapy among people with advanced-stage KS in Kenya.MethodsThis is a hybrid type III effectiveness-implementation study using a non-randomized, pre- post-design nested within a longitudinal cohort. We will compare the delivery of evidence-based chemotherapy for advanced-stage KS during the period before (2016–2020) to the period after (2021–2024), the rollout of a multicomponent patient navigation strategy. The multicomponent patient navigation strategy was developed in a systematic process to address key determinants of service penetration of and fidelity to chemotherapy in western Kenya and includes (1) physical navigation and care coordination, (2) video-based education, (3) travel stipend, (4) health insurance enrollment assistance, (5) health insurance stipend, and (6) peer mentorship. We will compare the pre-navigation period to the post-navigation period to assess the impact of this multicomponent patient navigation strategy on (1) implementation outcomes: service penetration (chemotherapy initiation) and fidelity (chemotherapy completion) and (2) service and client outcomes: timeliness of cancer care, mortality, quality of life, stigma, and social support. We will also describe the implementation process and the determinants of implementation success for the multicomponent patient navigation strategy.DiscussionThis study addresses an urgent need for effective implementation strategies to improve the initiation and completion of evidence-based chemotherapy in advanced-stage KS. By using a clearly specified, theory-based implementation strategy and validated frameworks, this study will contribute to a more comprehensive understanding of how to improve cancer treatment in advanced-stage KS.

Characteristics and Treatment Response of Patients with HIV Associated Kaposi's Sarcoma in Central Kenya.

Kaposi's sarcoma (KS) is the most common HIV-associated malignancy in Sub Saharan Africa. In 2018, it was the 7th most common cancer and the 10th most common cause of cancer death in Kenya. This study aimed to describe the baseline and clinical characteristics and treatment response observed following combined antiretroviral treatment (ART) and chemotherapy in KS patients. This was a descriptive analysis of patients aged ≥15 years treated for KS and HIV at 11 treatment hubs in Central Kenya between 2011 and 2014. Data on baseline and clinical characteristics, ART and chemotherapy regimens as well as treatment responses were collected from patient files and KS registers. A total of 95 patients presenting with clinically suspected KS with no history of prior treatment with chemotherapy were reviewed. All had histological diagnostic samples taken with 67 (71%) having confirmed KS. All were on ART, either newly initiated or continuing on ART, and 63 of the 67 (94.0%) confirmed to have KS received chemotherapy. Among the 67 patients with confirmed KS, mean age was 37.2 years (± 13.2) and 40 (59.7%) were male. More than 80% had normal baseline and follow-up BMI, and 34 (50.7%) were on a TDF-based regimen, 52 (77.6%) were treated with the Adriamycin, bleomycin and vinblastine protocol, and 55 (82.1%) had KS diagnosis before HIV diagnosis. All 67 patients had mucocutaneous lesions. Complete, partial response and stable disease occurred in 27 (40.3%), 10 (14.9%) and 7 (10.4%), respectively, 11 (16.4%) defaulted care during treatment, six patients died during treatment, four patients died before treatment while two patients had progressive disease during chemotherapy. The diagnosis of KS preceded HIV in the majority of cases reviewed, with histology helpful to reduce misdiagnosis. Patients generally complied with their chemotherapy, with overall good response rate for this intervention implemented at primary health-care facilities.

Malignant neoplasms in HIV patients in Russia: the story over a 20-year period

According to the official statistics, by the beginning of 2021, the overall number of registered HIV cases in Russia exceeded 1.1 million. For about 100 000 new HIV-infected patients have been registered annually in Russia recent years. Russia occupies one of the leading places in the incidence of HIV infection, and the growth rate of new HIV cases is not decreasing. HIV-infected patients have higher incidence of malignant neoplasms (MN) in comparison with the overall population and have the highest cancer mortality rates. The problem of HIV-associated malignancies is at the junction of two socially significant issues, and this situation especially taking into account in Russian Federation. The problems of diagnosis and treatment of MN are becoming topical, and it is extremely important to study HIV-associated malignancies epidemiology in the Russian Federation. This will help to create effective algorithms for organizing dispensary observation for HIV infected people, will help to early diagnosis of the disease, timely initiation of treatment and, as a result, will help to achieve the best oncological results.

Incidence, Treatment, and Outcome of HIV-Associated Hematologic Malignancies in People Living with HIV in Sweden.

People living with HIV (PLHIV) have an increased risk of hematologic malignancies (HMs). We aimed to characterize HMs among PLHIV at Karolinska University Hospital, Stockholm, Sweden. We studied all PLHIV receiving care at our center between 2004 and 2018. Data were retrieved retrospectively from InfCareHIV database and medical records. Around 3,484 patients received HIV care for a total of 22,903 person-years (py) with median follow-up of 7.6 years. HMs were identified in 43 patients with 30 cases of non-Hodgkin lymphoma (NHL), 9 cases of Hodgkin lymphoma (HL), 2 multicentric Castleman's disease, and 1 case each of myeloma and myelodysplastic syndrome. The incidence rate of NHL was 88/105 py and HL 39.6/105 py. The incidence of NHL declined 2004-2010 versus 2011-2018 (180.8 vs. 40.1/105 py; p = .001). Median time from HIV diagnosis to malignancy was shorter in NHL compared with HL (1.2 years vs. 8.9 years; p = .01) and effective HIV treatment was less common in NHL (33% vs. 100%; p < .001). The 5-year survival rate of NHL was 59% and HL 43%, significantly lower compared with lymphoma survival in the general population in Sweden. In the era of effective antiretroviral therapy (ART), the incidence rate of lymphoma was more than five times higher in PLHIV and 5-year survival significantly inferior. Efforts for earlier identification of HIV-infected individuals are likely to affect the incidence of NHL. Additionally, an effective screening for clinical and laboratory signs of HL in PLHIV on ART should be introduced to improve identification and survival of HL in this population.

A retrospective study of distribution of HIV associated malignancies among inpatients from 2007 to 2020 in China

HIV-associated malignancies are responsible for morbidity and mortality increasingly in the era of potent antiretroviral therapy. This study aimed to investigate the distribution of HIV-associated malignancies among inpatients, the immunodeficiency and the effect of antiretroviral therapy (ART) on spectrum of HIV-associated malignancies. A total of 438 cases were enrolled from 2007 to 2020 in Beijing Ditan Hospital. Demographic, clinical and laboratory data, managements, and outcomes were collected and analyzed retrospectively. Of 438 cases, 433 were assigned to non-AIDS-defining cancers (NADCs) (n = 200, 45.7%) and AIDS-defining cancers (ADCs) (n = 233, 53.2%), 5 (1.1%) with lymphoma were not specified further. No significant change was observed in the proportion of NADCs and ADCs as time goes on. Of NADCs, lung cancer (n = 38, 19%) was the most common type, followed by thyroid cancer (n = 17, 8.5%). Patients with ADCs had lower CD4 counts(104.5/μL vs. 314/μL), less suppression of HIVRNA(OR 0.23, 95%CI 0.16–0.35) compared to those with NADCs. ART did not affect spectrum of NADCs, but affect that of ADCs (between patients with detectable and undetectable HIVRNA). ADCs remain frequent in China, and NADCs play an important role in morbidity and mortality of HIV positive population.

A Plan for Emergency Shutdown and Reopening for a Consortium of Biobanks.

Background: The AIDS and Cancer Specimen Resource (ACSR) is a network of four regional biospecimen repositories and a technical core in the United States and South Africa. Its mission is to acquire, store, and distribute HIV-associated malignancy specimens and related clinical data to support translational research. At the outset of the COVID-19 pandemic, it became apparent that existing ACSR Standard Operating Procedures (SOPs) were not sufficient to ensure long-term maintenance and integrity of inventories during periods of extended shutdown. The ACSR needed an administrative SOP for situations pertaining to epidemics/pandemics. The ACSR Quality Working Group (QWG), comprised of representatives from each of the five ACSR sites and an external member who directs a large university medical center biorepository, addressed the issue. Methods: To understand the individual problems the sites faced, questions were developed to query each of the six QWG sites' contingency plans to cover this type of emergency, the amount of work allowed onsite and by whom, the challenges sites experienced, and the lessons learned to assist with future similar situations, while remaining consistent with the existing IRB protocols. Results: Reported challenges spanned all activities of classical biobanks and differed within the geographical locations of the sites and the local COVID-19 infection rate. Review of the responses to the questions revealed that the general shutdown of society external to the biorepositories presented them with a homogeneous collection of problems, limitations, and needs. This led to creating an SOP that addresses planning for pandemic emergencies, scaling down of activities, shutting down, and reopening plans. Conclusions: The ACSR QWG sites now have a structured response SOP for their sites, including guidance on how to develop and implement an emergency shutdown and reopening plan. The complete SOP is publicly available on the ACSR website.

HIV-1 Transactivator of Transcription (Tat) Co-operates With AP-1 Factors to Enhance c-MYC Transcription.

HIV-1 infection often leads to the development of co-morbidities including cancer. Burkitt lymphoma (BL) is one of the most over-represented non-Hodgkin lymphoma among HIV-infected individuals, and displays a highly aggressive phenotype in this population group, with comparatively poorer outcomes, despite these patients being on anti-retroviral therapy. Accumulating evidence indicates that the molecular pathogenesis of HIV-associated malignancies is unique, with components of the virus playing an active role in driving oncogenesis, and in order to improve patient prognosis and treatment, a better understanding of disease pathobiology and progression is needed. In this study, we found HIV-1 Tat to be localized within the tumor cells of BL patients, and enhanced expression of oncogenic c-MYC in these cells. Using luciferase reporter assays we show that HIV-1 Tat enhances the c-MYC gene promoter activity and that this is partially mediated via two AP-1 binding elements located at positions -1128 and -1375 bp, as revealed by mutagenesis experiments. We further demonstrate, using pull-down assays, that Tat can exist within a protein complex with the AP-1 factor JunB, and that this complex can bind these AP-1 sites within the c-MYC promoter, as shown by in vivo chromatin immunoprecipitation assays. Therefore, these findings show that in HIV-infected individuals, Tat infiltrates B-cells, where it can enhance the expression of oncogenic factors, which contributes toward the more aggressive disease phenotype observed in these patients.