This single-center retrospective study aimed to explore the 1-year mortality risk factors in 166 patients with human immunodeficiency virus (HIV)/acquired immune deficiency syndrome (AIDS) undergoing maintenance hemodialysis (MH) between 6 June 2017 and 6 June 2023, and construct a 1-year mortality prediction model. The patients were classified into survival and mortality groups based on the 1-year follow-up results, and into training and validation sets at a ratio of 1:1 (53 mortalities and 53 survivors in the training set and 48 mortalities and 58 survivors in the validation set). Stepwise logistic regression was used to construct a 1-year mortality prediction model and to visualize it as a nomogram. Receiver operating characteristic (ROC) analysis, calibration curves, and decision curves were used for nomogram evaluation in the training set and validation in the validation set. Age (≥52 years) (OR (95% CI): 2.05 (3.191-18.892), p < .001), neutrophil to albumin ratio (NAR) (≥0.135) (OR (95% CI): 4.753 (2.011-11.234), p < .001), and HIV-RNA (≥24,650) (OR (95% CI): 13.786 (5.493-34.598), p < .001), represents three of five independent risk factors of 1-year mortality in HIV/AIDS undergoing MH. The AUC of the nomogram for the training and validation sets were 0.908 (95% CI: 0.853-0.963) and 0.939 (95% CI: 0.896-0.983), respectively. The 1-year mortality prediction showed good separation capacity, calibration capacity, and clinical net benefit, which may benefit the management of patients with HIV/AIDS undergoing MH.

Antiretroviral therapy has transformed human immunodeficiency virus (HIV) infection from a fatal illness into a manageable chronic condition. However, despite remarkable progress, the HIV epidemic remains a global health challenge, with ambitious targets such as 95-95-95 by 2030 at risk of being unmet. While antiretroviral therapy availability has expanded worldwide, gaps persist, including unawareness of HIV status, inconsistent medication uptake, and limited engagement in care across diverse settings. Advanced HIV represents a particularly challenging yet underexplored aspect of HIV care. Its definition is complex, complicating efforts to address the needs of this vulnerable population. This review characterizes advanced HIV populations, defines them by spectra of immune suppression, antiretroviral therapy exposure, and drug resistance, and explores contemporary approaches to their management, with a particular focus on drug resistance and its clinical implications in modern HIV care. It highlights the unique challenges faced by individuals presenting late to care, those with limited care engagement, and aging populations with long-term exposure to HIV and antiretroviral therapy. By defining these populations, refining our understanding of advanced HIV, and addressing the diverse needs of affected individuals, providers can enhance outcomes and develop strategies to overcome barriers to care. Bridging these critical gaps is essential to advancing global efforts to end the HIV epidemic, both in the USA and worldwide.

To study the influence of the Affordable Care Act (ACA) policy and its Medicaid expansion on insurance status and survival in patients with HIV with aggressive lymphoma.

We used the National Cancer Database, a hospital-based national registry, to identify adults age 18-64 years with HIV-associated aggressive B-cell non-Hodgkin lymphomas (HIV-a-B-NHLs), diagnosed during 2007 to 2016. Survival analysis was performed on a subset of patients with HIV-a-B-NHL for whom location data were available who resided in Medicaid expansion-adopted and nonadopted states. Using a quasi-experimental difference-in-difference model, the difference in adjusted 2-year survival rates obtained with a flexible parametric Weibull model was compared for states that adopted the Medicaid expansion of ACA against those that did not adopt the expansion.

We identified 8,231 patients with HIV-a-B-NHL and 50,650 non-HIV patients with a-B-NHL. We found that a lower proportion of individuals were uninsured at diagnosis in the expansion states compared with nonexpansion states. We also found that the ACA policy adoption led to a reduction in the proportion of uninsured individuals with HIV-a-B-NHL in expansion states of 34.9%, compared with 15.9% in non-expansion-adopted states. There was a statistically significant improvement in the 2-year survival rate among patients with HIV-a-B-NHL in the expansion compared with nonexpansion states with the adoption of ACA (7.17% v 1.58%, P = .02).

Using a novel quasi-experimental model, we found that the ACA policy corresponded with a greater survival improvement in patients with HIV-a-B-NHL within Medicaid expansion-adopted states compared with nonexpansion states. We believe that this evidence should be taken into consideration in future policy making.

The reproductive system is a vital component of the human body. In modern society, due to various socio-economic reasons, an increasing number of couples are choosing to postpone childbearing. Research into the impact of aging on the reproductive system is becoming increasingly important. As people age, there is a decline in the reproductive system across various levels, from the testes in males to spermatogonia cells, and from the ovaries in females to oocytes. The aging of the reproductive system not only affects the system itself but also has implications for other organs and systems in the body. Conversely, the aging of other organs and systems can also damage the reproductive system. This review organizes the changes that occur within the reproductive system as a result of aging and focuses on the interactions between the reproductive system and other systems. Additionally, this review summarizes current therapies aimed at delaying aging, which may provide insights for future interventions targeting the aging of the reproductive system and other systems.

People living with HIV (PLWH) carry a higher risk of developing chronic liver disease and hepatocellular carcinoma (HCC). This relates to shared transmission pathways of HIV and viral hepatitis and a plethora of direct and indirect effects of HIV in the progression of chronic liver disease and HCC. In absence of active cancer treatment, the prognosis of PLWH affected by HCC is worse compared to matched controls without HIV. Evolving evidence suggests that PLWH may receive curative therapies including liver transplantation, loco-regional and systemic anti-cancer therapy for HCC with comparable benefit than people without HIV, underscoring that well controlled HIV infection should not be a barrier to the delivery of cancer care. Nevertheless, PLWH have historically been excluded from interventional clinical trials, and most of the evidence supporting clinical decision making in this population comes from small retrospective studies, adding further challenges to the management of PLWH affected by HCC. Furthermore, whether the biology of the tumour and its microenvironment is influenced by HIV and affects response to treatment is incompletely understood. In this review we summarise the current understanding of pathophysiology, screening and management of HCC in PLWH and discuss the persisting challenges and disparities in care which may contribute to clinical outcome in PLWH.

Kaposi's sarcoma (KS) is a malignant tumor primarily derived from endothelial cells. KS is the most common malignant tumor in AIDS patients and is aggressive. Kaposi sarcoma-associated herpesvirus (KSHV), also known as human herpesvirus 8 (HHV-8), is the etiological basis of KS. However, the underlying mechanism is still unclear. In this study, the KSHV virus was used to infect the human umbilical vein-fused endothelial cell line EAhy926 and the human ovarian microvascular endothelial cell line HOMEC. KSHV promoted the growth and invasion of endothelial cells and induced tumorigenesis in nude mice. Then, the growth-promoting and invasive effects of the protein replication and transcription activator (RTA) encoded by KSHV on endothelial cells were clarified. In addition, this study found that RTA can promote the expression of miR-155 by activating the activity of miR-155 promoter region. Previous studies have confirmed the inhibitory effect of miR-155 on GATA3 and GATA3 on STAT3. On this basis, this study made it clear that RTA can regulate the expression of miR-155/GATA3/STAT3, and then promote the growth and invasion of endothelial cells through this regulatory network. The purpose of this study is to explore the role of RTA in the growth and invasion of endothelial cells, as well as the regulation and specific regulation mechanism of RTA on the expression of miR-155/GATA3/STAT3, so as to determine whether RTA promotes the growth and invasion of endothelial cells through the regulation network of miR-155, so as to open up a new way for the treatment of diseases related to KSHV.

Epstein-Barr virus (EBV) contributes to over 200,000 cancers annually, predominantly aggressive lymphomas originating from hypoxic germinal centers (< 1% O2). However, conventional models fail to recapitulate the physiologically relevant hypoxic microenvironment which profoundly influences B-cell metabolic remodeling during transformation. Here, we establish an ex vivo model of EBV-driven B-cell transformation under 1% O2, demonstrating robust transformation and super-enhancer activation of oncogenic regulators, including MYC. Multi-omic analyses reveal distinct metabolic adaptations to hypoxia. Unlike normoxic B-cells, which rely on fatty acid desaturases and oxidation to mitigate lipotoxicity, hypoxically transformed B-cells suppress fatty acid synthesis while upregulating glycerophospholipid metabolism and lipid droplet formation to buffer excess saturated lipids. Consequently, these cells exhibit heightened dependence on external unsaturated fatty acids to support proliferation. Our findings provide the first physiologically relevant ex vivo model of EBV-driven B-cell transformation under hypoxia, uncovering metabolic vulnerabilities that could inform targeted therapeutic strategies for EBV-associated malignancies.

Background and Objectives: Kaposi's sarcoma (KS) is a rare malignancy with limited prospective data. The aim of this study was to evaluate the clinical features and prognostic factors of KS in a cohort of patients treated at a single center. Materials and Methods: Records of 83 patients with KS were retrospectively analyzed. Patient demographics, clinical features, and treatments were analyzed. Univariate and multivariate analyses were performed to evaluate factors affecting overall survival (OS). Results: The median age of the cohort was 65 years, and 22.9% were female. The classical type of KS was the most common (84.3%), with the most common site of localization being the feet (30.2%). The 5-year and 10-year OS rates were 82.7% and 70.8%, respectively. Univariate analysis identified age, performance score (ECOG PS), lymph node involvement, and disease stage as significant prognostic factors. However, in multivariate analysis, only the ECOG PS remained a significant predictor of OS. Conclusions: KS is a condition that requires long-term follow-up, and performance status is particularly critical for patient survival. In addition to our findings, comprehensive prospective studies are still needed to better understand the factors influencing patient survival in KS.

Approximately 39 million people live with HIV globally, with 1.3 million new infections annually. Despite improved treatment, noncommunicable diseases (NCDs) such as cardiovascular disease (CVD), neurological disorders, chronic kidney disease (CKD), and cancer are now the leading causes of death among people with HIV (PWH). Osteopontin (OPN) has emerged as a notable mediator in the inflammatory response to HIV and related NCDs. Our aim is to review the current understanding of OPN's role in HIV-related inflammatory pathways to highlight potential therapeutic avenues for improved treatment and mitigation of comorbidities.

We conducted a systematic review by searching relevant literature using specific keywords related to HIV, osteopontin, cardiovascular disease, inflammation, neurological disorders, cancer, and chronic kidney disease. The collected studies were organized and categorized by key themes, followed by a comprehensive analysis to identify patterns and draw conclusions regarding OPN's role in HIV-associated comorbidities.

The intricate interactions between OPN, its isoforms, and HIV-related illnesses suggest that OPN can exhibit both pro-inflammatory and anti-inflammatory roles, depending on the stage of the disease and the specific cell type involved. Its functions are diverse throughout the progression of HIV and its associated comorbidities, including CVD, CKD, cancer, and neurological disorders.

OPN's effects on the disease progression of HIV and related NCDs are highly variable due to its diverse functions. Therefore, further research is essential to fully understand its complex roles before considering OPN as a therapeutic target for HIV and its comorbidities.

Extrapulmonary tuberculosis (EPTB) is common among people living with HIV (PLWH). Abdominal ultrasound is an accessible investigation, frequently employed to support the diagnosis of EPTB, but may lead to misdiagnoses of diseases with overlapping clinical features, such as lymphoma.

To describe the abdominal ultrasound features and confirmed diagnoses of patients referred to a biopsy clinic with unexplained lymphadenopathy.

This was a retrospective descriptive study of patients attending the peripheral lymph node biopsy clinic at Groote Schuur Hospital between 2017 and 2020, who had abdominal ultrasound examinations while being investigated for unexplained lymphadenopathy. Ultrasound features were compared to the final diagnosis made on the lymph node biopsy.

Thirty-four patients were included, most of whom were PLWH (59%). Approximately one-third had a confirmed diagnosis of lymphoma (29%) and approximately one-third had a confirmed diagnosis of tuberculosis (32%). Splenic hypoechoic lesions were more common in patients with lymphoma (64%) than in patients with tuberculosis (46%) and malignancy (17%). Ascites was equally distributed between patients with tuberculosis (36%) and lymphoma (36%). The ultrasound report and confirmed diagnoses agreed in 40% of patients with tuberculosis. Additionally, 36% of patients with confirmed lymphoma were suspected to have tuberculosis based on the abdominal ultrasound.

Abdominal ultrasound abnormalities such as splenic hypoechoic lesions, lymphadenopathy, and ascites/pleural effusion have a differential diagnosis including both tuberculosis and lymphoma, and should be investigated accordingly.

Rhesus macaque rhadinovirus (RRV) is a primate gamma-2 herpesvirus (rhadinovirus) closely related to Kaposi sarcoma-associated herpesvirus (KSHV), the human oncovirus that causes Kaposi sarcoma. Like other herpesviruses, KSHV and RRV encode numerous envelope glycoproteins involved in cell attachment, entry, as well as assembly and release of progeny virions from infected cells. Two glycoproteins postulated to form a complex and reported to be virus-neutralizing targets are glycoproteins M (gM) and N (gN). To investigate gM and gN in rhadinovirus infection, we utilized infectious and pathogenic bacterial artificial chromosomes (BAC). RRV BACmids with nonsense mutations introduced into gM or gN did not yield an infectious virus. However, when gM or gN of RRV were exchanged for gM or gN from KSHV, each of the KSHV-chimeric RRV BACmids restored virus replication and infectious spread. Interestingly, we also discovered that the substitution of KSHVgM into the RRV BACmid was associated with attenuation in viral spread, an effect that was not countered by a double-chimeric virus. In contrast, the substitution of RRV gN into a KSHV BACmid negatively affected the assembly of KSHV, independent of gM/gN complex formation. Therefore, here, we revealed that in KSHV and RRV, gM and gN are interchangeable, contribute to crucial functions for viral assembly and spread, and have evolved in a virus-specific manner. Although more research is needed to define the roles of gM and gN, our work establishes the first glycoprotein-chimeric viruses for KSHV and RRV, which can now be used to corroborate gM/gN as targets for a cancer vaccine.IMPORTANCEKaposi sarcoma (KS) is a human cancer caused by KSHV and is one of the most frequently occurring cancers in HIV/AIDS patients, as well as in regions where KSHV is endemic. In this report, we have constructed and authenticated the first KSHV glycoprotein-encoding chimeric viruses for evaluations in the RRV/rhesus macaque model and have also uncovered fundamental roles for the glycoproteins gM and gN. Our work is significant by successfully bridging the human-specific, species barrier that has previously restricted preclinical evaluations of the KSHV glycoproteins as vaccine targets in vivo. Although there is no KSHV-specific animal model that is widely used, these KSHV-chimeric viruses may be useful as tools to guide future vaccine design and strategy as vaccine candidates progress toward clinical trials.

Burkitt's lymphoma (BL) affecting the female genital tract is rare.

The aim of this paper is to report BL of the cervix in an HIV-positive patient to discuss the fatality of the condition and ways to mitigate it through advocacy for improved health care delivery in resource limited settings.

The patient was a 29-year-old woman, Para 1, with abnormal vaginal bleeding for a month and living with HIV and had a CD4 of 26 cells/μL. The histological examination of the cervical biopsy confirmed an extra-nodal BL. She had International Federation of Gynecology and Obstetrics (FIGO) stage 3B cervical cancer based on presence of hydronephrosis and pelvic wall involvement. The patient was reviewed at the oncology multidisciplinary meeting and required chemoradiation. There was delay in her management due to a long waiting list for chemoradiation at oncology unit in the referral center and the patient demised 43 days after diagnosis and did not receive the treatment.

This case suggests that women living with HIV who have BL should be fast-tracked for treatment as HIV viremia may worsen the prognosis of the malignancy. Following the encounter with the index patient an advocacy action plan has been made by the oncology multidisciplinary team to prioritize the treatment of women with aggressive histological types of cervical cancer.

A long waiting list for chemoradiation in low resource settings may delay management of advanced BL of the cervix. Inadequate cervical cancer screening and delays in diagnosis are other barriers to the care of women with aggressive cervical cancers in low resource settings. Systemic changes in healthcare delivery are therefore required in many low resource settings. Advocacy for patients particularly those with aggressive diseases using the index case as a point of reference is ideal and should be promoted in resource-limited settings to improve health care delivery.

In East and Southern Africa, treatment of people with concomitant cancer and HIV is complicated by siloed service delivery pathways, which exacerbate barriers to care and impact clinical decision-making. Integrating HIV care into cancer treatment centers may improve service delivery and overall patient outcomes.

We administered a questionnaire to clinicians and support staff at tertiary cancer referral centers in Malawi, Zimbabwe, Uganda, and South Africa to assess level of concern about clinical management of people with HIV (PWH) and cancer, barriers to integrating HIV service delivery into cancer treatment delivery, and beliefs related to HIV, antiretroviral therapy (ART), and integrated care.

Of 195 clinician and support staff participants, 165 (85 %) were direct providers of cancer-associated care. Over 50 % indicated that they held concerns about survival, treatment complications, co-morbidities, and drug-drug interactions in PWH compared to patients without HIV. Over 80 % agreed that knowing cancer patients' HIV status, ART status, and ART regimen would facilitate better care and should be considered in cancer care decision-making. Overall, respondents were optimistic that HIV-related care could be easily integrated into cancer care provision. The most-frequently endorsed barriers to integrated care were workspace limitations, disruptions to workflow, availability of staff, and cost to the hospital and to patients.

Cancer clinicians and support staff report overall positive attitudes toward integrating HIV and cancer service delivery. Research to elucidate service delivery pathways and contextualize system-based barriers to integrating care are critical next steps to optimize linked HIV and cancer care delivery.

The overall incidence of lymphomas associated with HIV infection is low, and only few hematological oncology specialties provide standardized treatment. Newly diagnosed patients with impaired immune function have a high incidence of complications, such as infections during induction chemotherapy, which increases treatment difficulties. For patients with relapse/refractory status, salvage treatment options are extremely limited, because new drug clinical trials are lacking. At present, both domestic and international clinical practices have shown that patients with lymphomas associated with HIV infection can achieve long-term survival after standardized combination antiretroviral therapy (cART) with targeted immunochemotherapy, followed by autologous hematopoietic stem cell transplantation (auto-HSCT) immediately after achieving complete remission. In recent years, some new drugs, such as XPO1 inhibitors, immune checkpoint inhibitors, antibody-drug conjugates (ADC drugs), bispecific antibodies, and small-molecule drugs, have been tentatively incorporated into treatment regimens for patients with lymphomas associated with HIV infection, and preliminary clinical data have been obtained. Based on two patients with lymphomas associated with HIV infection who were admitted to our center, this study proposed a standardized diagnostic and treatment pathway and provided corresponding references for clinicians to apply new drugs. The aim of this study was to promote diagnostic and treatment capabilities and improve the survival and quality of life of patients of lymphomas associated with HIV infection in China.

Background/Objectives: People living with HIV (PLWH) are more susceptible than immunocompetent people to non-melanoma skin cancers. These tumors can arise de novo or from precancerous lesions, such as actinic keratosis (AKs). The management of AKs in PLWH has not been widely discussed in the literature. More specifically, the efficacy of the treatment of AKs in PLWH with modern topical drugs, such as tirbanibulin, is limited. The present work aims to evaluate the response rate to the intervention with tirbanibulin 1% ointment for treating AKs in PLWH. Methods: We retrospectively collected the data of the PLWH who visited the Dermatology Department of the Policlinico Riuniti (Foggia, Italy) between September 2023 and September 2024. PLWH who received the diagnosis of AKs and underwent treatment with tirbanibulin 1% ointment were studied. To assess the severity of AKs, the number of AKs and the AKs' area and severity index (AKASI) score were calculated at the time of diagnosis (T0) and after treatment (T1). Results: Ten PLWH were found to have AKs and received topical therapy with tirbanibulin 1% ointment. On average, at T0, the number of lesions was 8.2 and the AKASI score was 4.20; at T1, the number of AKs was 1.7 and the AKASI score was 1.5. Only two patients reported a mild inflammatory reaction to applying tirbanibulin 1% ointment. Conclusions: The rate of satisfactory responses was in line with a recent multicentric Italian study performed on immunocompetent patients. Our results confirm the efficacy and tolerability of tirbanibulin 1% ointment in treating AKs in PLWH in particular.

It is widely accepted that cancer mostly arises from random spontaneous mutations triggered by environmental factors. Our theory challenges the idea of the random somatic mutation theory (SMT). The SMT does not fit well with Charles Darwin's theory of evolution in that the same relatively few mutations would occur so frequently and that these mutations would lead to death rather than survival of the fittest. However, it would fit well under the theory of evolution, if we were to look at it from the vantage point of pathogens and their supporting microbial communities colonizing humans and mutating host cells for their own benefit, as it does give them an evolutionary advantage and they are capable of selecting genes to mutate and of inserting their own DNA or RNA into hosts. In this article, we provide evidence that tumors are actually complex microbial communities composed of various microorganisms living within biofilms encapsulated by a hard matrix; that these microorganisms are what cause the genetic mutations seen in cancer and control angiogenesis; that these pathogens spread by hiding in tumor cells and M2 or M2-like macrophages and other phagocytic immune cells and traveling inside them to distant sites camouflaged by platelets, which they also reprogram, and prepare the distant site for metastasis; that risk factors for cancer are sources of energy that pathogens are able to utilize; and that, in accordance with our previous unifying theory of disease, pathogens utilize melanin for energy for building and sustaining tumors and metastasis. We propose a paradigm shift in our understanding of what cancer is, and, thereby, a different trajectory for avenues of treatment and prevention.

The clinical management of people with multidrug-resistant (MDR) human immunodeficiency virus (HIV) remains challenging despite continued development of antiretroviral agents. A 58-year-old male individual with MDR HIV and Kaposi sarcoma (KS) was treated with a new antiretroviral regimen consisting of anti-CD4 domain 1 antibody UB-421 and capsid inhibitor lenacapavir. The individual experienced delayed but sustained suppression of plasma viremia and a substantial increase in the CD4+ T cell count. A longitudinal examination of plasma HIV and infectious isolates showed no evidence of viral evolution or the emergence of UB-421- or lenacapavir-resistant viruses. The individual received three cycles of liposomal doxorubicin and five doses of anti-programmed cell death protein 1 (PD-1) monoclonal antibody pembrolizumab that resulted in improvement in KS with flattening of lesions. Our data demonstrate that combination therapy with UB-421 could provide sustained virologic suppression in people harboring MDR HIV with limited therapeutic alternatives.

The Epstein-Barr virus (EBV) infects nearly 90% of adults globally and is linked to over 200,000 annual cancer cases. Immunocompromised individuals from conditions such as primary immune disorders, HIV, or posttransplant immunosuppressive therapies are particularly vulnerable because of EBV's transformative capability. EBV remodels B cell metabolism to support energy, biosynthetic precursors, and redox equivalents necessary for transformation. Most EBV-driven metabolic pathways center on mitochondria. However, how EBV regulates B cell mitochondrial function and metabolic fluxes remains unclear. Here, we show that EBV boosts cardiolipin (CL) biosynthesis, essential for mitochondrial cristae biogenesis, via EBV nuclear antigen 2/MYC-induced CL enzyme transactivation. Pharmacological and CRISPR genetic analyses underscore the essentiality of CL biosynthesis in EBV-transformed B cells. Metabolomic and isotopic tracing highlight CL's role in sustaining respiration, one-carbon metabolism, and aspartate synthesis. Disrupting CL biosynthesis destabilizes mitochondrial matrix enzymes pivotal to these pathways. We demonstrate EBV-induced CL metabolism as a therapeutic target, offering synthetic lethal strategies against EBV-associated B cell malignancies.

Gammaherpesviruses are DNA tumor viruses that establish lifelong latent infections in lymphocytes. For viruses such as Epstein-Barr virus and murine gammaherpesvirus 68, this is accomplished through a viral gene-expression program that promotes cellular proliferation and differentiation, especially of germinal center B cells. Intrinsic host mechanisms that control virus-driven cellular expansion are incompletely defined. Using a small-animal model of gammaherpesvirus pathogenesis, we demonstrate in vivo that the tumor suppressor p53 is activated specifically in B cells latently infected by murine gammaherpesvirus 68. In the absence of p53, the early expansion of murine gammaherpesvirus 68 latency greatly increases, especially in germinal center B cells, a cell type whose proliferation is conversely restricted by p53. We identify the B cell-specific latency gene M2, a viral promoter of germinal center B cell differentiation, as a viral protein sufficient to elicit a p53-dependent anti-proliferative response caused by Src-family kinase activation. We further demonstrate that Epstein-Barr virus-encoded latent membrane protein 1 similarly triggers a p53 response in primary B cells. Our data highlight a model in which gammaherpesvirus latency gene-expression programs that promote B cell proliferation and differentiation to facilitate viral colonization of the host trigger aberrant cellular proliferation that is controlled by p53.

Overexpression of aspartic proteases, as cathepsin D, is an independent marker of poor prognosis in breast cancer, correlated with the incidence of clinical metastasis. We aimed to find if HIV-1 aspartic protease (PR) can play a similar role. Murine adenocarcinoma 4T1luc2 cells were transduced with lentivirus encoding inactivated drug-resistant PR, generating subclones PR20.1 and PR20.2. Subclones were assessed for production of reactive oxygen species (ROS), expression of epithelial-mesenchymal transition (EMT) factors, and in vitro migratory activity in the presence or absence of antioxidant N-acetyl cysteine and protease inhibitors. Tumorigenic activity was evaluated by implanting cells into BALB/c mice and following tumor growth by calipering and bioluminescence imaging in vivo, and metastases, by organ imaging ex vivo. Both subclones expressed PR mRNA, and PR20.2, also the protein detected by Western blotting. PR did not induce production of ROS, and had no direct effect on cell migration rate, however, treatment with inhibitors of drug-resistant PR suppressed the migratory activity of both subclones. Furthermore, expression of N-cadherin and Vimentin in PR20.2 cells and their migration were enhanced by antioxidant treatment. Sensitivity of in vitro migration to protease inhibitors and to antioxidant, known to restore PR activity, related the effects to the enzymatic activity of PR. In vivo, PR20.2 cells demonstrated higher tumorigenic and metastatic activity than PR20.1 or parental cells. Thus, HIV-1 protease expressed in breast cancer cells determines their migration in vitro and metastatic activity in vivo. This effect may aggravate clinical course of cancers in people living with HIV-1.

Kaposi sarcoma herpesvirus (KSHV) is an oncogenic DNA virus associated with various malignancies, including tumours like Kaposi sarcoma and Primary effusion lymphoma. Recently, the importance of the tumour microenvironment in KSHV-associated tumours is being studied. New studies utilizing human primary cells, co-culture experiments with KSHV-infected cells, and modern techniques like time-resolved single cell analysis, have significantly advanced the understanding of KSHV interactions with monocytes and macrophages. These cells play key roles in shaping the tumour microenvironment. It has become clear that KSHV-infected endothelial cells regulate the growth and the differentiation of monocytes and macrophages. Monocytes and macrophages, in turn, can regulate KSHV-infected cells in tumorigenesis and cytokine secretion, leading to the pro-tumour microenvironment. Further investigations into the viral regulation of monocytes and macrophages thus have potential to lead to the discovery of novel antitumour therapeutics.

Classic Hodgkin lymphoma (CHL) is an extremely common non-acquired immunodeficiency syndrome (AIDS) defining malignancy and its incidence is rising. CHL is usually present in the lymph node and extranodal involvement is rare. Primary CHL of the gastrointestinal (GI) tract is exceedingly rare.

In this case, a patient with human immunodeficiency virus (HIV)/AIDS and disseminated leishmaniasis presented with a small bowel mass leading to bowel perforation. Histologically, the small bowel mass showed a transmural infiltrate of scattered large atypical multinucleated cells surrounded by histiocytes and T-cells. Initial differential diagnosis was wide due to the unusual presentation and cytologic atypia of the tumor cells. Identifying the Hodgkins Reed-Sternberg (HRS) cells with their unique immunophenotype was key for diagnosis.

It is critical to identify secondary CHL in HIV/AIDS patients especially in the presence of immunodeficiency and disseminated opportunistic infection. Extranodal primary GI tract CHL is exceedingly rare and thus awareness of this entity, which can mimic many other tumors, especially in immunocompromised individuals, is important. Special stains and cultures are helpful for the diagnosis, and antimicrobial therapy will induce successful clinical outcome. Overall, the unusual combination of acute clinical presentation, leishmaniasis, and HIV made the histological recognition of CHL crucial to avoid misdiagnosis and guide successful clinical management.

People with HIV (PWH) are living longer and experiencing a greater burden of morbidity from non-AIDS-defining conditions. Chronically treated HIV disease is associated with ongoing systemic inflammation that contributes to the development of chronic conditions (eg, cardiovascular disease) and geriatric syndromes (eg, frailty). Apart from HIV disease, a progressive increase in systemic inflammation is a characteristic feature of biologic aging, a process described as "inflammaging." Inflamm-aging is driven by persistent antigen stimulation and stress, leading to an immune profile characterized by elevated levels of blood inflammatory markers and cellular activation and senescence. Chronic HIV disease is hypothesized to accentuate the immune profile of inflamm-aging, in part through viral persistence in lymphatic tissues, permanent injury impairing immune recovery, the presence of copathogens, gut dysbiosis and microbial translocation, and chromosomal and genetic alterations associated with immune activation. Few strategies exist for safe and effective modulation of systemic inflammation among older PWH. The strongest current evidence supports aggressive management of modifiable risk factors such as lipids, blood pressure, and levels of physical activity. Future inflamm-aging research should be directed toward advancing the implementation of proven approaches, such as physical activity, as well as studying novel mechanisms of, and treatments for, inflamm-aging among PWH.

Patients with lymphoma may require intensive care (ICU) because of disease- or treatment-related complications. The lymphoma-HIV interaction complicates management, but whether outcomes are worse in these patients, when critically ill, is unclear. A retrospective observational cohort study reviewed outcomes of patients admitted to ICU, subsequent 5-year survival, and prognostic factors.

Academic ICU at the UK National Centre for HIV Malignancy.

Records between 2007 and 2020 identified the following cohorts: HIV lymphoma, lymphoma alone, HIV alone, and patients without HIV/lymphoma. Patient demographics, lymphoma characteristics, ICU admission data, and survival outcomes were collected. Five-year survival outcomes were analyzed for the lymphoma cohorts. ICU outcomes were analyzed for all cohorts. Descriptive statistics summarized baseline characteristics and outcomes. Multivariate regression identified factors associated with ICU mortality.

Of 5929 patients admitted to the ICU, 63 had HIV lymphoma and 43 had lymphoma alone. Survival to ICU discharge was 71% and 72%, respectively. Adjusted log-odds ratio for ICU survival was significantly better in the comparator cohort. ICU survival between the HIV lymphoma and lymphoma-alone cohorts was not significantly different. Adjusted 5-year survival was not significantly different between lymphoma cohorts. Factors independently associated with a worse ICU survival prognosis were emergency admissions, Acute Physiology and Chronic Health Evaluation II score, initial lactate, and day requiring level 3 support. Mechanical ventilation and higher Acute Physiology and Chronic Health Evaluation II scores were independent risk factors for worse 5-year survival in the lymphoma cohorts.

ICU outcomes and 5-year survival rates of patients with lymphoma were unaffected by HIV status, revealing favorable outcomes in patients with HIV-related lymphoma admitted to the ICU.

Combination antiretroviral therapy (ART) has improved outcomes for human immunodeficiency virus (HIV) associated non-Hodgkin lymphoma. This is an analysis of 127 patients with HIV with Burkitt lymphoma (HIV-BL) and diffuse large B-cell lymphoma (HIV-DLBCL) treated at the Zhongnan Hospital of Wuhan University over a 17-year period during the ART and rituximab era. The median CD4 count for the cohorts was 0.141 × 109/L (range, 0.001-0.861 × 109/L). DA-EPOCH ± R (54%) were most commonly used in HIV-BL. CHOP± R (42%) was most commonly used to treat HIV-DLBCL. The complete response rate after first-line curative therapy was 10/28 (36%) in HIV-BL and 25/57 (44%) in HIV-DLBCL. The 2-year progression-free survival (PFS) and overall survival (OS) for the HIV-BL cohort was 50% and 41% respectively. The 2-year PFS and OS for the HIV-DLBCL cohort was 55% and 47% respectively. Current China practice favours the treatment of HIV-BL and HIV-DLBCL similarly to the HIV-negative population with the use of concurrent ART. However, due to the extremely low percentage of patients receiving ART prior to the lymphoma diagnosis, the high percentage of patients with poor performance status, and the advanced stage at diagnosis, the treatment of HIV-related lymphoma remains the major challenge in China.

"When you can measure what you are speaking about, and express it in numbers, you know something about it." is a famous quote attributed to Lord Kelvin. This sentiment puts viral load measurements at the center of virology. Viral load, or more precisely, DNA copy number measurements, are also used to follow infections with human herpesviruses, such as Kaposi sarcoma herpesvirus (KSHV) and Epstein-Barr Virus (EBV). EBV and KSHV are associated with human cancers, and determining their DNA copy numbers in the context of cancer prediction and progression on therapy is of fundamental scientific and translational interest. Yet, there is no generally accepted assay for KSHV DNA quantitation, and KSHV viral load is not used in clinical decision-making. Here, we review the history of KSHV DNA detection assays, explore factors that affect sensitivity and specificity, and describe an automated, high-throughput, real-time quantitative polymerase chain reaction (PCR) assay for KSHV and EBV. In conjunction with a digital PCR assay using the same primer/probe combination, we describe how to determine the absolute KSHV genome copy numbers in plasma, peripheral blood mononuclear cells, saliva, and other easily accessible body fluids.

In people living with HIV (PLWH), the susceptibility to malignancies is notably augmented, with lymphoma emerging as a predominant malignancy. Even in the antiretroviral therapy (ART) era, aggressive B-cell lymphoma stands out as a paramount concern. Yet, the pathogenesis of HIV related lymphoma (HRL) largely remains an enigma. Recent insights underscore the pivotal role of the dysregulated B cell receptor (BCR) signaling cascade, evidencing its oncogenic potential across a spectrum of lymphomas. Intricate interplays between HIV and BCR structural-functional integrity have been identified in PLWH. In this review, we elucidated the mechanism by which the BCR signaling pathway is involved in HRL, mainly including the following aspects: HIV can reshape BCR structure by modulating of activation-induced cytidine deaminase (AID) and recombination-activating gene (RAG) dynamics; HIV can act as a chronic antigen to activate the BCR signaling pathway, such as upregulating PI3K and MAPK signaling pathway and reducing the expression of CD300a; HIV co-infection with other oncogenic viruses may also influence tumor formation mediated by the BCR signaling pathway. This review aims to elucidate the intricate regulation of the BCR signaling pathway by HIV in B cell lymphoma, providing a novel perspective on the pathogenesis of lymphoma in HIV-affected environments.

Cancers represent the primary cause of mortality among people living with HIV (PLWH). However, comprehensive nationwide data regarding cancer incidence remains limited. Our objective was to evaluate the incidence rates of cancers, particularly those associated with human papillomavirus (HPV), within a nationwide study cohort. Using data from the Estonian Health Insurance Fund and the National Cancer Registry from 2004 to 2021, we calculated standardized incidence ratios (SIRs) for various cancer types among PLWH to compare to the general population with special emphases on HPV-associated cancers. A total of 7011 individuals (65.7% men) diagnosed with HIV were identified. HPV-associated cancers accounted for 21.4% of all incident cancer cases among PLWH. SIRs for HPV-associated cancers were 3.7 [95% confidence interval (CI) 2.2-6.2] among men living with HIV (MLWH) and 5.7 (95% CI 4.0-7.9) among women living with HIV (WLWH). In MLWH, the highest SIRs were for penile 12.5 (95% CI 4.0-38.7), followed by oropharyngeal 3.6 (95% CI 1.7-7.6) and anal-rectal cancers 2.7 (95% CI 1.1-6.4) in comparison to the general population. In WLWH, an increased incidence of cervical (SIR = 5.8, 95% CI 3.9-8.5), oropharyngeal (SIR = 6.1, 95% CI 1.5-24.3), and anal-rectal (SIR = 3.6, 95% CI 1.2-11.2) cancers was observed. A significantly increased risk of AIDS-defining and non-AIDS-defining cancers is reported. We demonstrate a substantially heightened risk of HPV-associated cancers among PLWH compared to the general population, underscoring the imperative for intensified screening and scaled-up vaccination along with improvement in adherence to antiretroviral therapy.

The Acquired Immunodeficiency Syndrome Professional Group of the Society of Infectious Diseases of the Chinese Medical Association formulated the first edition of the Chinese Guidelines for the Diagnosis and Treatment of human immunodeficiency virus (HIV)/acquired immune deficiency syndrome (AIDS) (referred to as the Guidelines) in 2005. The 2024 edition of the Guidelines has been compiled by updating the 2021 fifth edition, incorporating the latest research advancements in antiviral therapy, comprehensive management, opportunistic infections, concurrent tumors, and the prevention and intervention of HIV infection. The new edition also introduces a new section on "Incomplete immune reconstitution", proposes the concept of "HIV vulnerable populations" for the first time with recommendations for their diagnosis and treatment. This edition of the Guidelines covers 14 sections: epidemiology, pathogenic characteristics, laboratory tests, pathogenesis, clinical presentation and staging, diagnostic criteria, common opportunistic infections, antiretroviral therapy, immune reconstitution inflammatory syndrome, incomplete immune reconstitution, AIDS-related neoplasms, prevention of mother-to-child transmission and conception in serodiscordant couples, pre- and post-exposure prophylaxis, and whole-course management of HIV infection. This edition of the Guidelines aims to assist clinical physicians in making informed decisions in the diagnosis, treatment, and management of HIV/AIDS and will be periodically revised and updated based on domestic and international research progress.

Individuals with HIV experience an increased risk of lymphoma, making this an important cause of death among people with HIV. Nevertheless, little is known regarding the underlying genetic aberrations, which we therefore set out to characterize.

We conducted next-generation panel sequencing to explore the mutational status of diagnostic lymphoma biopsies from 18 patients diagnosed with lymphoma secondary to HIV infection.

Ion Torrent next-generation sequencing was performed with an AmpliSeq panel on diagnostic lymphoma biopsies from HIV-associated B-cell lymphomas ( n  = 18), comprising diffuse large B-cell lymphoma ( n  = 9), classic Hodgkin lymphoma ( n  = 6), Burkitt lymphoma ( n  = 2), follicular lymphoma ( n  = 1), and marginal zone lymphoma ( n  = 1). The panel comprised 69 lymphoid and/or myeloid-relevant genes, in which either the entire coding sequence or a hotspot region was sequenced.

Among the 18 lymphomas, we detected 213 variants. The number of detected mutations ranged from 4 to 41 per tumor distributed among 42 genes, including both exonic and intronic regions. The most frequently mutated genes included KMT2D (67%), TNFAIP3 (50%), and TP53 (61%). Notably, no gene was found to harbor variants across all the HIV-associated lymphomas, nor did we find subtype-specific variants. While some variants were shared among patients, most were unique to the individual patient and were often not reported as malignant genetic variants in databases.

Our findings demonstrate genetic heterogeneity across histological subtypes of HIV-associated lymphomas and thus help elucidate the genetics and pathophysiological mechanisms underlying the disease.

Human immunodeficiency virus (HIV) infection screening and diagnosis are critical to control the HIV epidemic. Testing for anti-HIV antibodies (Ab) and antigens (Ag) in blood samples is the first step to screen people who have been potentially exposed to the virus. This study aimed to evaluate the performance of the MAGLUMI HIV Ab/Ag Combi for detection of HIV antibodies and antigens.

We used residual samples to assess the diagnostic specificity and sensitivity of the MAGLUMI HIV Ab/Ag Combi retrospectively. All samples that met the test criteria were tested with the MAGLUMI HIV Ab/Ag Combi according to manufacturer's instruction. Results of the MAGLUMI HIV Ab/Ag Combi were compared with the Architect HIV Ag/Ab Combo test.

The specificity of the MAGLUMI HIV Ab/Ag Combi was 99.85% in 5,057 unselected blood donors and 100.00% in 213 hospitalized patient samples, respectively. The sensitivity of the Test in 614 HIV-1 Ab, HIV-1 Ag or HIV-2 Ab positive samples was 100.00%. Seroconversion sensitivity from results of 30 panels was comparable between the MAGLUMI HIV Ab/Ag Combi and the Architect assay.

The reactivity of the MAGLUMI HIV Ab/Ag Combi test is comparable to the Architect HIV Ag/Ab Combo assay.

Immune checkpoint inhibitors (ICI) have changed the prognostic outlook for several malignancies. Despite the unprecedented durable responses and improvement in survival outcomes with ICIs, exclusion of oncology patients living with human immunodeficiency virus (HIV) from most ICI-related trials has limited utility of these agents. Clinical outcomes related to concomitant use of antiretroviral therapy and ICI remain unclear. We present a case series based on our institution's experience to address this unmet need of clinical outcomes with ICI in oncology patients living with HIV.

Electronic medical records were queried to identify patients living with HIV who were also diagnosed with cancer and treated with ICI from May 2019 to September 2022.

A total of five patients were on concurrent antiretroviral therapy and immunotherapy. From an efficacy perspective, three patients were observed to have a response (one complete response, one partial response, and one stable disease). There were three patients with known cluster of differentiation (CD4 + ) levels who had an increase in CD4  +  cell count with ICI treatment. The HIV viral load remained undetected in most of the patients on ICI treatment. No confirmed immune-related adverse effects were documented for any patients in this review.

Immune checkpoint inhibitors may be efficacious and tolerable for treatment of cancer in patients living with HIV. Upward trends in CD4  +  cell counts observed in this case series suggest that immune checkpoint inhibitors may enhance HIV disease control. Further research is needed for this patient population to supply more robust evidence for clinical practice.

A diverse range of viruses have well-established roles as the primary driver of oncogenesis in various haematological malignancies and solid tumours. Indeed, estimates suggest that approximately 1.5 million patients annually are diagnosed with virus-related cancers. The predominant human oncoviruses include Epstein-Barr virus (EBV), Kaposi sarcoma-associated herpesvirus (KSHV), hepatitis B and C viruses (HBV and HCV), human papillomavirus (HPV), human T-lymphotropic virus type 1 (HTLV1), and Merkel cell polyomavirus (MCPyV). In addition, although not inherently oncogenic, human immunodeficiency virus (HIV) is associated with immunosuppression that contributes to the development of AIDS-defining cancers (specifically, Kaposi sarcoma, aggressive B cell non-Hodgkin lymphoma and cervical cancer). Given that an adaptive T cell-mediated immune response is crucial for the control of viral infections, increasing research is being focused on evaluating virus-specific T cell therapies for the treatment of virus-associated cancers. In this Review, we briefly outline the roles of viruses in the pathogenesis of these malignancies before describing progress to date in the field of virus-specific T cell therapy and evaluating the potential utility of these therapies to treat or possibly even prevent virus-related malignancies.

Hematopoietic stem cell transplant (HSCT) is now recognized as a standard treatment option for people with HIV (PWH) who develop high-risk hematologic malignancies. However, the involved polypharmacy can lead to complications from drug interactions and toxicities, affecting the efficacy and safety of chemotherapy and antiretroviral therapy (ART). Managing these patients requires a personalized approach, including the careful selection of ART based on previous therapies and potential interactions, alongside risk assessment for infections. This discussion will address the history of HSCT in PWH and management considerations for this group.

SUMMARYWithin weeks of the first report of acquired immunodeficiency syndrome (AIDS) in 1981, it was observed that these patients often had Kaposi sarcoma (KS), a hitherto rarely seen skin tumor in the USA. It soon became apparent that AIDS was also associated with an increased incidence of high-grade lymphomas caused by Epstein-Barr virus (EBV). The association of AIDS with KS remained a mystery for more than a decade until Kaposi sarcoma-associated herpesvirus (KSHV) was discovered and found to be the cause of KS. KSHV was subsequently found to cause several other diseases associated with AIDS and human immunodeficiency virus (HIV) infection. People living with HIV/AIDS continue to have an increased incidence of certain cancers, and many of these cancers are caused by EBV and/or KSHV. In this review, we discuss the epidemiology, virology, pathogenesis, clinical manifestations, and treatment of cancers caused by EBV and KSHV in persons living with HIV.

Individuals who identify as lesbian, gay, bisexual, transgender, queer, intersex, or gender-nonconforming (LGBTQ+) experience discrimination and minority stress that may lead to elevated cancer risk.

In the absence of population-based cancer occurrence information for this population, this article comprehensively examines contemporary, age-adjusted cancer risk factor and screening prevalence using data from the National Health Interview Survey, Behavioral Risk Factor Surveillance System, and National Youth Tobacco Survey, and provides a literature review of cancer incidence and barriers to care.

Lesbian, gay, and bisexual adults are more likely to smoke cigarettes than heterosexual adults (16% compared to 12% in 2021-2022), with the largest disparity among bisexual women. For example, 34% of bisexual women aged 40-49 years and 24% of those 50 and older smoke compared to 12% and 11%, respectively, of heterosexual women. Smoking is also elevated among youth who identify as lesbian, gay, or bisexual (4%) or transgender (5%) compared to heterosexual or cisgender (1%). Excess body weight is elevated among lesbian and bisexual women (68% vs. 61% among heterosexual women), largely due to higher obesity prevalence among bisexual women (43% vs. 38% among lesbian women and 33% among heterosexual women). Bisexual women also have a higher prevalence of no leisure-time physical activity (35% vs. 28% among heterosexual women), as do transgender individuals (30%-31% vs. 21%-25% among cisgender individuals). Heavier alcohol intake among lesbian, gay, and bisexual individuals is confined to bisexual women, with 14% consuming more than 7 drinks/week versus 6% of heterosexual women. In contrast, prevalence of cancer screening and risk reducing vaccinations in LGBTQ+ individuals is similar to or higher than their heterosexual/cisgender counterparts except for lower cervical and colorectal cancer screening among transgender men.

People within the LGBTQ+ population have a higher prevalence of smoking, obesity, and alcohol consumption compared to heterosexual and cisgender people, suggesting a higher cancer burden. Health systems have an opportunity to help inform these disparities through the routine collection of information on sexual orientation and gender identity to facilitate cancer surveillance and to mitigate them through education to increase awareness of LGBTQ+ health needs.

The unique case study presented here explores an exceptionally rare occurrence in an HIV-positive female-synchronous diagnoses of anal squamous cell carcinoma and diffuse large B cell lymphoma (DLBCL) of the stomach. With limited existing literature on such clinical scenarios, this case serves as an unprecedented insight into the complexities of managing such synchronous malignancies in HIV-positive patients. The article also examines the heightened risk of specific cancer types in individuals living with HIV compared to those without the virus, focusing on AIDS-defining cancers such as Kaposi sarcoma, various lymphomas (including Burkitt lymphoma, immunoblastic lymphoma, and primary central nervous system lymphoma), and invasive cervical cancer. Additionally, it highlights an increased incidence and severity of other cancers amongst HIV-positive individuals, including Hodgkin lymphoma, anal cancer, testicular cancer, melanoma, various skin and superficial eye cancers, and leiomyosarcoma. The article discusses the challenges in the treatment plan, the impact of HIV status on the patient's condition, and the evolving landscape of cancer risk in people living with HIV. Despite significant progress in HIV care, cancer remains a paramount health concern for this population, necessitating tailored approaches and further research to ensure improved outcomes for individuals facing this dual challenge. The case highlights the need for greater inclusivity of PLWH in cancer clinical trials and reinforces the importance of equitable cancer care for this unique patient demographic.

Human herpesvirus 8 (HHV-8) infection shows obvious regional and ethnic differences. Although studies have shown that these differences may be associated with lipid metabolism, to date, no large-scale studies have explored this. This study explored the seropositivity rate of HHV-8 among 2516 residents from 10 regions of northwest China and then the correlates of HHV-8 infection with lipid profile. The HHV-8 serological positivity rate was 15.6% among all residents. The HHV-8 seroprevalence ranged 11.2-27.6% among different ethnicities. Across different BMI levels, the positive rates of HHV-8 were 27.6%, 16.9%, and 13.6% for a BMI < 18.5, 18.5-24.9, and ≥25, respectively. HHV-8 seropositivity rate was lower for hypertensive people (12.6%) than for non-hypertensive people (16.7%). Univariate logistic regression analyses revealed that age, hypertension, systolic blood pressure, BMI, total cholesterol, and high-density lipoprotein cholesterol (HDL-C) significantly correlated with HHV-8 seropositivity (p < 0.05). Multivariate logistic regression analysis after adjusting for confounding factors showed that HDL-C (odds ratio [OR]: 0.132, 95% confidence interval [CI], 0.082-0.212; p < 0.001) and BMI (OR: 0.959, 95% CI 0.933-0.986; p = 0.003) were associated with HHV-8 seropositivity. Subgroup analyses concerning ethnicity, sex, or age demonstrated a consistent relationship with HDL-C. The results of HHV-8 seropositivity and BMI were inconsistent in the subgroups. However, Spearman's correlation analysis between HHV-8 serum antibody titer and HDL-C levels showed no linear relationship among HHV-8 seropositive individuals (ρ = -0.080, p = 0.058). HHV-8 serum antibody titers were also not significantly correlated with BMI (ρ = -0.015, p = 0.381). Low HDL-C levels may be an independent risk factor for HHV-8 infection, but there is no significant correlation between HDL-C levels and HHV-8 antibody titers.

This study aimed to investigate the association between obesity and cancer risk as well as site-specific cancer risks in adults with HIV using a nationwide health screening database in Korea.

Of the 16,671 adults with a new diagnosis of HIV from 2004 to 2020, 456 incident cancer cases and 1814 individually matched controls by sex, year of birth, year of HIV diagnosis, and follow-up duration (1 : 4 ratio) were included in this nested case-control study. The association between obesity (BMI ≥25 kg/m 2 ) and cancer risks was estimated and presented as odds ratios (ORs) and 95% confidence intervals (95% CIs).

Of the 456 cancer incident cases, there were 146 AIDS-defining cancer cases and 310 non-AIDS-defining cancer cases. Compared with nonobese adults with HIV, obese adults with HIV were at higher risk of non-AIDS-defining cancer (OR = 1.478, 95% CI = 1.118-1.955). Otherwise, the overall risk of AIDS-defining cancer (OR = 0.816, 95% CI = 0.520-1.279) and each type of AIDS-defining cancer (Kaposi sarcoma and non-Hodgkin's lymphoma) were not high in obese adults with HIV. Of the specific types of non-AIDS-defining cancers, obesity was associated with an increased risk of colorectal cancer (OR = 3.090, 95% CI = 1.110-8.604) and liver, bile duct, and pancreatic cancers (OR = 2.532, 95% CI = 1.141-5.617).

Obesity, which is one of the important health concerns in HIV management, was associated with an increased risk of non-AIDS-defining cancer but not AIDS-defining cancer.

Kaposi sarcoma is a vascular tumor that affects the pulmonary system. However, the diagnosis of airway lesions suggestive of pulmonary Kaposi sarcoma (pKS) is reliant on bronchoscopic visualization. We evaluated the role of Kaposi sarcoma herpesvirus (KSHV) viral load in bronchoalveolar lavage (BAL) as a diagnostic biomarker in patients with bronchoscopic evidence of pKS and evaluated inflammatory cytokine profiles in BAL and blood samples.

In this retrospective study, we evaluated KSHV viral load and cytokine profiles within BAL and blood samples in patients who underwent bronchoscopy for suspected pKS between 2016 and 2021.

KSHV viral load and cytokine profiles were obtained from both the circulation and BAL samples collected at the time of bronchoscopy to evaluate compartment-specific characteristics. BAL was centrifuged and stored as cell pellets and KSHV viral load was measured using primers for the KSHV K6 gene regions.

We evaluated 38 BAL samples from 32 patients (30 with HIV co-infection) of whom 23 had pKS. In patients with airway lesions suggestive of pKS, there was higher KSHV viral load (median 3188 vs. 0 copies/10 6 cell equivalent; P  = 0.0047). A BAL KSHV viral load cutoff of 526 copies/10 6 cells had a sensitivity of 72% and specificity of 89% in determining lesions consistent with pKS. Those with pKS also had higher IL-1β and IL-8 levels in BAL. The 3-year survival rate for pKS patients was 55%.

KSHV viral load in BAL shows potential for aiding in pKS diagnosis. Patients with pKS also have evidence of cytokine dysregulation in BAL.