Setting Of Human Immunodeficiency Virus Research Articles

Therapeutic Modulation of Arginase with nor-NOHA Alters Immune Responses in Experimental Mouse Models of Pulmonary Tuberculosis including in the Setting of Human Immunodeficiency Virus (HIV) Co-Infection.

L-arginine metabolism is strongly linked with immunity to mycobacteria, primarily through the antimicrobial activity of nitric oxide (NO). The potential to modulate tuberculosis (TB) outcomes through interventions that target L-arginine pathways are limited by an incomplete understanding of mechanisms and inadequate in vivo modeling. These gaps in knowledge are compounded for HIV and Mtb co-infections, where activation of arginase-1 due to HIV infection may promote survival and replication of both Mtb and HIV. We utilized in vitro and in vivo systems to determine how arginase inhibition using Nω-hydroxy-nor-L-arginine (nor-NOHA) alters L-arginine pathway metabolism relative to immune responses and disease outcomes following Mtb infection. Treatment with nor-NOHA polarized murine macrophages (RAW 264.7) towards M1 phenotype, increased NO, and reduced Mtb in RAW macrophages. In Balb/c mice, nor-NOHA reduced pulmonary arginase and increased the antimicrobial metabolite spermine in association with a trend towards reduced Mtb CFU in lung. In humanized immune system (HIS) mice, HIV infection increased plasma arginase and heightened the pulmonary arginase response to Mtb. Treatment with nor-NOHA increased cytokine responses to Mtb and Mtb/HIV in lung tissue but did not significantly alter bacterial burden or viral load. Our results suggest that L-arginine pathway modulators may have potential as host-directed therapies to augment antibiotics in TB chemotherapy.

A National Cancer Database Analysis of Demographics, Treatment Patterns and Survival Trends of Patients with Plasmablastic Lymphoma in US: Does Ethnicity Predict Enhanced Outcomes?

Background: Plasmablastic lymphoma (PbL) is an exceedingly rare, aggressive non-Hodgkin lymphoma with overlapping features of myeloma and lymphoma diagnosed most commonly in immunocompromised individuals, especially in the setting of human immunodeficiency virus (HIV) and Epstein-Barr virus (EBV) infection ( Int J Lab Hematol PMID 36074710). Pathologically, it is characterized by lacking CD20 and PAX5 expression with the presence of CD38, CD138, MUM1/IRF4, Blimp1, and XBP1 expression ( Blood Lymphat Cancer PMID 31360094). There is no established standard of care ( Blood PMID 25636338). Due to the disease's rarity, limited information is available on PbL, especially when focusing on underrepresented minorities. This study aims to describe the demographics, treatment patterns, and survival outcome differences in Hispanic (HI) versus non-Hispanic (NH) patients in the United States with PbL. Methods: Data was analyzed on patients with PbL in the US reported to the NCDB between 2010 and 2019. Sociodemographic and treatment characteristics were compared between ethnic groups. Kaplan-Meier and Cox regression analyses were used to compare overall survival (OS) between HI and NH populations. Multivariate analysis and propensity score matching were performed with adjustment for age, stage, co-morbidity score, insurance status, type of facility and great circle distance. Results: Between 2010 and 2019, 1624 patients were diagnosed with PbL with 16% identified as HI. HI were diagnosed at a younger median age of 48 years as compared to NH at 58 years. Diagnosis was made predominately in males (78%) with no statistical difference between HI and NH. Most HI and NH were white (92% and 74% in HI and NH, respectively) with increased racial diversity among NH. 17% of all patients identified as black with 1% HI and 21% NH. Regarding income, 32% HI had an income less than $38,000 versus 23% NH; whereas, 31% NH had an income greater than $63,000 versus 20% HI [p=0.017]. 38% HI had a Charlson-Deyo Comorbidity Index score ≥ 2 as compared to 27% NH [p<0.001]. Table 1 provides additional information on demographics. 45% of all patients had stage IV disease at the time of diagnosis. 86% of all patients received treatment with no statistical difference among HI and NH [p=0.246]. 67% of HI were treated at academic/research programs compared to 50% of NH [p=0.004]. The median distance between the patient's residence and treatment facility was 6.9 miles for HI versus 9.8 miles for NH [p=0.001]. The survival probability at 2, 5, and 10 years for HI was 59%, 52%, and 42%, respectively as compared to NH was 47%, 37%, and 31%, respectively. The median survival time (MS) was 9.4 years in HI versus 1.4 years in NH [p <0.001]. Figure 1 shows the Kaplan Meier curve comparing overall survival (OS) between HI versus NH.When adjusted on multivariate analysis, there were no independent variables associated with better or worse OS; moreover, propensity matched analysis showed no MS difference between HI vs NH (1.79 years versus 1.17 years). Conclusion: This hospital-based analysis noted that HI presented with PbL at a younger age than NH; however, HI more frequently had a higher Charlson-Deyo Comorbidity Index score than NH. There was no statistical difference in the stage at diagnosis between HI and NH. Additionally, HI had a lower income and no medical insurance as compared to NH suggesting HI possibly had inferior access to medical resources. Paradoxically, HI had significantly higher OS rates. Further insight into the disease's intrinsic characteristics, as well as biological factors, is needed to gain a better understanding of these poor outcomes.

The impact of psoriasis biologic therapy on HIV viral load andCD4+ cell counts in HIV-positive individuals: A real-world cohort study.

Psoriasis is a chronic immune-mediated inflammatory disorder that also occurs in the setting of human immunodeficiency virus (HIV). Biological therapy has transformed the treatment landscape for psoriasis; however, individuals with HIV are excluded from clinical trials. The impact of biological therapy on blood parameters in HIV is unclear and is only observed in small case series. The aim of this study was to assess the effect of biological therapy in psoriasis vulgaris in individuals with well-controlled HIV on CD4+ cell counts, CD4+ proportion and HIV viral load over 12 months. This retrospective cohort study was conducted at a tertiary referral centre in Sydney, Australia and included 36 HIV-positive individuals with psoriasis treated with biological therapy, compared with 144 age-, gender- and HAART-matched individuals without psoriasis seen between 2010 and 2022. Outcomes of interest included HIV viral load, CD4+ cell count and incidence of infections. No statistically significant difference was seen in baseline HIV viral load and CD4+ count between individuals with and without psoriasis. No significant change in CD4+ count or HIV viral load was seen over the 12-month period of analysis in the HIV cohort without psoriasis. The HIV cohort treated with biological therapy for psoriasis also did not demonstrate any significant change in HIV viral load and CD4+ counts over the 12-month period examined. Stratification by type of biological therapy used did not identify any significant changes in these parameters. Rates of infections and adverse events were also not significantly different between cohorts. It is possible that minor blips seen in the biologics cohort may be a risk factor for future virological failure, and future prospective longitudinal studies are required. In individuals with well-controlled HIV, the use of biological therapy for psoriasis does not significantly impact HIV viral load, CD4+ cell count, CD4+ proportion and rates of infection over the first 12 months of therapy.

CD8 Encephalitis in HIV: A Review of This Emerging Entity.

Encephalitis is a life-threatening neurological condition with multiple causes in the setting of Human Immunodeficiency Virus (HIV). CD8 Encephalitis (CD8E) is a newly recognised condition which can present in an acute manner, with pertinent features including classical radiological findings with an intense brain parenchymal infiltration of CD8+ T cells. This review attempted to clarify the symptomatology, distribution and determinants of this condition, as well as to examine its vast unknowns. A literature review was undertaken in July 2022, utilising the PubMed and Google Scholar databases. Papers published between 2006-2022 were reviewed. Eighteen papers, totalling 57 patients, were found and analysed. Statistical analysis was undertaken using Chi-squared and Wilcoxon rank-sum tests as appropriate, with p < 0.05 deemed significant. In this review, 57 patients were identified, with a female (61%, 34/56) and Black African (70%, 40/57) preponderance. Females were more likely to present with headache (p = 0.006), and headache was more likely to be present in those who died (p = 0.02). There was no statistically significant association between baseline CD4 count (p = 0.079) and viral load (p = 0.72) with disease outcome. Overall, 77% (41/53) of patients had classical imaging findings, including bilateral gadolinium-enhancing punctate and perivascular white matter lesions. However, many patients (23/57) required a brain biopsy as part of their diagnostic workup. Corticosteroid treatment was commonly prescribed in patients (64%, 35/55) and had a mortality benefit, with an overall survival in this group of 71% (p = 0.0008). In those who died, median survival was 5.5 months. In rare instances, recurrence of the disease was noted, which responded poorly to treatment. CD8E represents a new and complex condition with few risk factors identified for its occurrence. The presenting symptoms are broad, but headache appears to be more common in females and more significantly associated with death. Though rare, CD8E is likely under-diagnosed, possibly due to overlapping features with other illnesses and lack of physician experience in its recognition and management. Corticosteroids demonstrate a clear mortality benefit, but more studies are required to determine their optimal dosing and duration, as well as the use of steroid-sparing agents. Further reviews should help to better determine the risk factors for the condition, as well as non-invasive biomarkers, to aid in diagnosis and help to predict poor prognosis and disease recurrence.

Abdominal pain and fever in a patient with human immunodeficiency virus: a case report

BackgroundNeutropenic enterocolitis (NE), or typhlitis, a condition typically associated with severe neutropenia in the setting of chemotherapy, is highly morbid (50–100%) and benefits from early diagnosis. It has been associated with neutropenia in the setting of human immunodeficiency virus (HIV) but has not been described in a patient with HIV who was not neutropenic on presentation. We present the case of a patient with HIV who was not neutropenic on presentation but found to have NE.Case presentationA 27-year-old male with a history of HIV on antiretroviral therapy and epilepsy presented with concern for breakthrough seizure. The patient revealed he was having non-bloody, non-bilious emesis and diarrhea for 3 days. Initial labs were white blood cell count 3.9 × 109/L, absolute neutrophil count (ANC) 3.14 × 109/L, CD4 count 290 cells/mm3, and undetectable viral load. A computed tomography (CT) scan of the abdomen/pelvis with contrast revealed wall thickening of the cecum and proximal ascending colon (Fig. 1), suggestive of NE. The patient was started on cefepime and metronidazole but switched to piperacillin/tazobactam after he became leukopenic/neutropenic.ConclusionsNeutropenic enterocolitis, typically presenting with fever, abdominal pain, and hematochezia, can be difficult to identify, particularly in patients without a history of malignancy. However, it should be considered in patients with HIV presenting with these symptoms, even with a normal ANC and CD4 count above 200 cells/mm3. Prompt diagnosis can be made with CT, and early initiation of broad-spectrum antibiotics greatly reduces the risk of morbidity/mortality.

COVID-19 outcomes in patients with cancer and HIV: An analysis of the COVID-19 and Cancer Consortium (CCC19).

e18790 Background: Patients with SARS-CoV-2 with a diagnosis of cancer have increased risk of severe COVID-19 outcomes compared to patients without cancer. However, little is known regarding outcomes of patients with COVID-19 and cancer in the setting of human immunodeficiency virus (HIV). Given the unique risks of this population, we sought to understand COVID-19 outcomes using registry data. Methods: This is a descriptive research study utilizing the CCC19 registry, an international multi-institutional registry with healthcare provider-reported cases of patients with cancer and COVID-19. Between March 2020-December 2021, 116 persons with HIV (PWH) and 10,642 persons without HIV (PWOH) with laboratory-confirmed SARS-CoV-2 infection were identified as eligible for the analysis. Results: Median follow-up time for both groups was 90 days, with interquartile range (IQR) 30-180 days. Most PWH were actively receiving antiretroviral therapy (ART) at the time of COVID-19 diagnosis, with 71% (n = 82) having named drug information available; bictegravir/emtricitabine/tenofovir was the most common ART (n = 25). PWH were of younger age (median 57.5 yrs [IQR 46.5-63.25] vs 65 yrs [IQR 55-74]), male (81% vs 47%), and either non-Hispanic Black or Hispanic (71% vs 34%) compared to PWOH. 12% of PWH (n = 14) were current smokers compared to 6% of PWOH (n = 638), and more than half in each group were never smokers (51% of PWH and 53% of PWOH). The following comorbidities were identified in PWH vs PWOH: cardiovascular (16% vs 20%), pulmonary (16% vs 20%), renal (15% vs 14%), and diabetes mellitus (18% vs 27%). A higher proportion of PWH had hematologic malignancy compared to PWOH (33% vs 19%). More PWH had active cancer which was progressing at the time of SARS-CoV-2 infection compared to PWOH (24% vs 14%). 44% of PWH (n = 51) had received active systemic anticancer therapy within the 3 months preceding SARS-CoV-2 infection (including cytotoxic, targeted, endocrine therapies, and immunotherapy) compared to 51% of PWOH (n = 5,420). PWH had an increased rate of hospitalization (58% vs 55%) compared to PWOH. Although a lower proportion of PWH required supplemental oxygen during hospitalization compared to PWOH (34% vs 38%) and ICU admission rates were identical between the two groups (16% vs 16%), PWH had an increased rate of mechanical ventilation (14% vs 10%) and death (24% vs 18%) compared to PWOH. Conclusions: This is the first known study describing outcomes of patients with cancer and COVID-19 in the PWH population from a large multinational dataset. PWH have characteristics associated with adverse outcomes in prior analyses (male sex, non-Hispanic Black or Hispanic, hematologic malignancy, progressing cancer) but are notably younger and have fewer comorbidities. HIV infection may portend increased risk of severe COVID-19 and death; however, additional analyses, including multivariable regression, are warranted.

Brief Report of Anti–Programmed Cell Death Protein-1 in Human Immunodeficiency Virus Setting: Relevant and Breaking Results in First-Line NSCLC Therapy

In the recent past, we observed an increased risk of cancer in the population with human immunodeficiency virus (HIV) owing to the development of antiretroviral therapies that decreased mortality caused by HIV-specific infections. This particularly fragile population is frequently excluded from clinical trials, and up-to-date recommendations for these patients are lacking. Only few cases of patients with HIV suffering from cancer and undergoing first-line immunotherapy have been reported so far. Here, we report the largest known study of patients with HIV with NSCLC (five patients) undergoing first-line immunotherapy by pembrolizumab, after CANCERVIH group selection. Our results are consistent with those of previous case reports concerning safety of immunotherapy in patients with HIV, revealing no severe or fatal toxicity, opportunistic infections, or immune reconstitution inflammatory syndrome. Moreover, pembrolizumab did not seem to modify HIV viral parameters. We also evaluated the effectiveness of immunotherapy in these HIV-immunosuppressed patients: the average survival was 9.8 months, with three patients having rapid progression and two partial response. Nevertheless, besides safety and drug-to-drug interactions, the effectiveness of first-line immunotherapy in people living with HIV needs to be supported by larger studies.

A SHOCKING CASE OF DISSEMINATED TB

TOPIC: Critical Care TYPE: Medical Student/Resident Case Reports INTRODUCTION: BH is a 41-year-old Nepalese male with a history of ulcerative colitis (recently on adalimumab) and type two diabetes mellitus was transferred for the evaluation of ECMO. He presented to an outside hospital two days prior with a complaint of fevers, hemoptysis, and five-pound weight loss over one month. Despite pre-biologic testing showing indeterminate interferon, negative acid fast culture and a normal chest x-ray, a CT scan of his chest revealed diffuse miliary pattern, consistent with tuberculosis. CASE PRESENTATION: On arrival, the patient was intubated and required norepinephrine, vasopressin and phenylephrine to maintain mean arterial pressures over 65 mmHg. White blood cell count was 5.75 K/uL, lactic acid was 6.5 mmol/L, troponin was 0.5 ng/mL, brain natriuretic peptide was 66,716 pg/mL, ALT of 2827 unit/L and AST greater than 7000 unit/L, concerning for shock. Patient was anuric for which continuous renal replacement therapy was initiated. An echocardiogram showed an ejection fraction of 20-25%. Dobutamine was started due to a rising lactate despite adequate blood pressure. Patient was not a candidate for ECMO given presumed TB infection. Patient was started on Amikacin, Moxifloxacin, Meropenem, Ethambutol and Amphotericin. After a week, he was weaned from pressors and was extubated. He also regained renal function. A repeat echocardiogram two weeks following demonstrated improvement of ejection fraction to 50%. Acid fast bacillus testing confirmed tuberculosis. DISCUSSION: Adalimumab, a TNF-α inhibitor, are among biologic medications that are used in treatment of ulcerative colitis. Although one of its main infectious complications is tuberculosis, there can be other side effects including initiation of heart failure, cytopenia, and elevated transaminases [4]. All mentioned side effects may worsen the clinical picture of septic shock. There are only a handful of cases, some in pediatric literature [3], that conveys the degree of sepsis related to disseminated tuberculosis. Most literature of disseminated tuberculosis are often in the setting of human immunodeficiency virus or in pediatrics [4]. CONCLUSIONS: This case highlights the atypical presentation of disseminated tuberculosis masquerading as septic shock in the setting of recent adalimumab use. Despite the negative screen, it may be possible to develop tuberculosis during biologic therapy. Our case suggests that it may be of utility to retest for tuberculosis during therapy in individuals who may be at high risk for developing tuberculosis or those with indeterminant interferon results. REFERENCE #1: George S, Papa L, Sheils L, Magnussen CR. Septic shock due to disseminated tuberculosis. Clin Infect Dis. 1996 Jan;22(1):188-9. doi: 10.1093/clinids/22.1.188. PMID: 8825004. REFERENCE #2: Hess S, Hospach T, Nossal R, Dannecker G, Magdorf K, Uhlemann F. Life-threatening disseminated tuberculosis as a complication of TNF-α blockade in an adolescent. Eur J Pediatr. 2011 Oct;170(10):1337-42. doi: 10.1007/s00431-011-1501-y. Epub 2011 May 31. PMID: 21625932. REFERENCE #3: Mark S. Godfrey, Lloyd N. Friedman, Tuberculosis and Biologic Therapies: Anti-Tumor Necrosis Factor-α and Beyond, Clinics in Chest Medicine, Volume 40, Issue 4, 2019, Pages 721-739, ISSN 0272-5231, ISBN 9780323682152, https://doi.org/10.1016/j.ccm.2019.07.003.[4] Scheinfeld N. Adalimumab: a review of side effects. Expert Opin Drug Saf. 2005 Jul;4(4):637-41. doi: 10.1517/14740338.4.4.637. PMID: 16011443. DISCLOSURES: No relevant relationships by Saad Ashraf, source=Web Response No relevant relationships by Fiyad Haniff, source=Web Response No relevant relationships by ANDRY VAN DE LOUW, source=Web Response

Presternal Scrofuloderma: Tip of the Iceberg Unveiling Multifocal Extrapulmonary Tuberculosis - A Rare Case Report

Introduction: Scrofuloderma, a type of secondary cutaneous tuberculosis (TB) commonly arising from the underlying cervical or axillary lymph node foci via contiguity, is frequent in the pediatric population. The origin of scrofuloderma from the underlying sternal tubercular osteomyelitic focus is exceptionally unusual. It can rarely be a part of the convoluted riddle of multifocal TB, particularly in the setting of human immunodeficiency virus (HIV) infection. Case Presentation: We hereby report a 16-year-old immunocompetent female who presented with chronic, sinus-like lesions with bridging scars on the upper chest, clinically confounded with infected keloid and deep fungal infection. She was later diagnosed with scrofuloderma arising from sternal osteomyelitis compounded with multifocal tuberculosis (sternal, mediastinal, cutaneous, lumbar vertebral) and received antitubercular treatment. Conclusions: This case highlights the importance of harboring clinical scepticism supported by thorough systemic investigations while diagnosing these innocuous mimickers occurring at rare sites, even in immunocompetent individuals.

The spectrum of the cytopathological features of primary effusion lymphoma and human herpes virus 8-related lymphoproliferative disorders.

Human herpes virus 8-related lymphoproliferative disorders are a complex and heterogeneous group of entities and some of them are eminently diagnosed by cytopathology. In a routine laboratory, these lesions account for less than 1% of the effusion fluids samples. However, they represent up to 30% of all the lymphoma diagnosis from effusion cytological samples and their consideration in the diagnostic flow chart is mandatory, especially in human immunodeficiency virus-positive patients. A retrospective series of cytological specimens from cavity effusions (n=605) were analysed. Five human herpes virus 8-related lymphoproliferative processes were recruited. A combination of morphological criteria (enhanced with May-Grünwald Giemsa staining), cell block-based immunocytochemistry and flow cytometry were undertaken for final characterisation. The identification of malignant cells may be difficult. Some specimens are particularly rich, easily leading to suspect a lymphoproliferative process, whereas in other cases, the presence of abundant reactive mesothelial cells, histiocytes, neutrophils, small reactive T and B lymphocytes may obscure the neoplastic process. The biological behaviour may be very heterogeneous and a standardised therapy for these cases is still lacking, although some patients may benefit from antiretroviral therapy in a human immunodeficiency virus setting. The present case series highlights some characteristic findings of these entities to reaffirm useful cytopathological diagnostic criteria, stressing the crucial role of the appropriate technical processing of effusion fluids to obtain the best performances.

The role of human immunodeficiency virus in the pathogenesis of vernal keratoconjunctivitis-like disease in adults: A demographic and epidemiological study

Purpose:The purpose was to identify and describe patients with new-onset vernal keratoconjunctivitis-like (VKC-like) disease after puberty.Methods:The study consisted of two parts: a prospective observational descriptive study of patients with new-onset VKC-like disease, and a case-control study to determine the relationship of a CD4 count with VKC-like disease in adults, in the setting of human immunodeficiency virus (HIV). Patients were recruited between January 2016 and November 2017 from a Provincial Eye hospital, one of two large referral hospitals in KwaZulu-Natal, South Africa. Patients presenting to the eye clinic were screened and diagnosed at the Primary Eye Care Unit. Inclusion criteria: age 15 years and older with signs and symptoms of new-onset VKC-like disease. Exclusion criteria: a history of childhood atopic diseases, atopic keratoconjunctivitis and patients who declined HIV testing. Data collected included HIV status, CD4 count, antinuclear antibodies and total serum immunoglobulin E.Results:Thirty-three patients were included; females n = 16 and males n = 17. The mean age at presentation was 32.45 ± 9.93 years, 95% CI = 28.94–35.97. Twenty-six patients (78.8%) were HIV positive, 95% CI (62–89). The proportion of HIV positive patients was statistically different from the HIV negative group, Chi-squared = 21.866, P value <0.0001. In the group of HIV positive patients, 72% were classified as immunodeficient according to their CD4 counts. An association was proven between severely immunodeficient patients and the risk of VKC-like disease (Chi-squared = 4.992, P value = 0.0255).Conclusion:In this cohort, a statistically significant association was found between VKC-like disease in adults and an HIV positive status. This association calls for more research on the subject.

Marginal Zone Lymphoma, Immune Dysregulation, and High-Grade Transformation

Abstract Marginal zone lymphoma (MZL) is a low-grade B-cell lymphoma, which includes mucosa-associated lymphoid tissue lymphoma, splenic MZL, and nodal MZL. Of these, mucosa-associated lymphoid tissue lymphoma is the most frequent. While all 3 subtypes are typically indolent, a subset undergoes transformation to an aggressive B-cell lymphoma resulting in treatment challenges and a worse prognosis. We present a patient with systemic lupus erythematosus and Sjögren disease who developed MZL while on cyclophosphamide and steroids for treatment of her autoimmune disease. Her MZL was associated with a relatively indolent initial course. Unfortunately, her systemic lupus erythematosus continued to progress, and she ultimately required a renal transplant for end-stage renal disease due to lupus nephritis. At transplant, her MZL was thought to be in remission, but shortly thereafter, she developed an enlarging neck mass. A biopsy demonstrated background MZL with focal transformation to diffuse large B-cell lymphoma. Evidence is emerging that the underlying biology of a subset of MZL based on mutational profile, gene expression, and/or cytogenetic factors may affect the risk of transformation. Immune status has not been linked to progression, but chronic inflammation and immune dysregulation in the setting of chronic infection or autoimmune disease may underlie MZL development. In addition, iatrogenic immunosuppression for solid organ transplant or acquired immunodeficiency in the setting of human immunodeficiency virus may also result in increased risk or unusual presentations of MZL. This article features a case-based approach to explore factors related to MZL progression in a patient with a complex history of autoimmunity and immune suppression.

Treatment of Central Nervous System Manifestations of HIV in the Current Era

Treatment of neurological, neurocognitive, and neuropsychiatric impairment in the setting of human immunodeficiency virus (HIV) infection remains a complex problem, given several possible mechanisms of pathogenesis. The etiology must be determined based on clinical judgment and objective evidence, including cerebrospinal fluid (CSF) data from lumbar puncture and neuroimaging information from magnetic resonance imaging, when available and indicated. Other neuroinfectious etiologies must be ruled out, including central nervous system (CNS) opportunistic infections. HIV replication in the CNS (including CSF escape) should be evaluated for and excluded. If CSF HIV is detected, we recommend a treatment switch to antiretrovirals (ARVs) targeted to address any CSF HIV resistance mutations identified, or empiric treatment intensification using ARVs with high CNS penetration. If CSF HIV is not detected, treatment intensification with CCR5 inhibitors may be considered as an adjunct to reduce neuroinflammation. Finally, the current ARV regimen must be examined for possible neurotoxicity. Efavirenz has been well-recognized for its neuropsychiatric adverse effects and potential for causing sleep disturbances. Similar concerns have recently been raised with integrase inhibitors, especially dolutegravir and raltegravir, although further studies are needed to determine the risks for clinically relevant neuropsychiatric side effects from these medications, given their overall high potency and proven success in treating systemic HIV.

Use of Cerebrospinal Fluid (1,3)-β-d-Glucan to Monitor Treatment Response in Candida albicans Meningitis in an HIV-infected Patient

Abstract Candida meningitis is rare in the setting of human immunodeficiency virus (HIV) infection and often presents a diagnostic challenge. Its clinical features typically mimic those of cryptococcal or tuberculous meningitis and Candida can be difficult to culture from cerebrospinal fluid. Furthermore, optimal treatment and monitoring parameters are not well defined. Cerebrospinal fluid levels of (1,3)-β-d-glucan, which is a component of the fungal cell wall, have been used to diagnose and monitor response to therapy in other cases of fungal meningitis, but its utility in the setting of Candida meningitis and HIV infection is less clear. Here, we present a case of spontaneous Candida albicans meningitis in a woman with advanced HIV infection and report on the clinical utility of cerebrospinal fluid (1,3)-β-d-glucan for diagnosis and monitoring of chronic infection.

Abstract 3243: Associations of polyomavirus seroreactivity with AIDS-related non-Hodgkin's lymphoma

Abstract Background: Human polyomaviruses have a suspected role in carcinogenesis. In the setting of human immunodeficiency virus (HIV) infection, coinfection with MCV polyomavirus is associated with high risk of Merkel cell carcinoma. A role in lymphomagenesis has also been suggested by studies in the general population, but there are no prior studies in individuals with the acquired immunodeficiency syndrome (AIDS). Methods: We measured antibodies against 11 common polyomaviruses in archived serum and plasma samples from two prospective cohort studies of HIV infection. Patients with incident (n=28) and prevalent (n=38) AIDS-related non-Hodgkin lymphoma (NHL) were matched by age, sex, and CD4 count to 67 HIV-positive AIDS-free controls. Seroreactivity was measured by fluorescent bead-based multiplex serology, quantified as median fluorescence intensity (MFI). Logistic regression models were used to estimate adjusted odds ratios (ORs) and 95% confidence intervals (95% CIs) for NHL risk. Multinomial logistic regression compared incident and prevalent NHL cases to lymphoma-free controls and heterogeneity between case groups was evaluated by Wald tests. Differences in MFI were assessed by Kruskal-Wallis tests. Based on log-transformed MFI values for 15 masked duplicate samples, estimated coefficients of variation (CV) were &amp;lt;20% and intraclass correlation coefficients (ICC) were &amp;gt;90% for all antibodies except LPV (CV 29%, ICC 67%). Results: Cases had significantly lower prevalence of antibodies to WU polyomavirus than lymphoma-free controls (64% vs. 85%), with OR 0.28 (95% CI 0.12-0.68). Cases had non-significantly lower prevalence of antibodies to JC, TSV, MCV and KI polyomaviruses (ORs 0.42-0.71); similar prevalence of antibodies to BK, HPyV6 and HPyV7 polyomaviruses (ORs 0.98-1.18); and non-significantly higher prevalence of antibodies to HPyV10, LPV and HPyV9 polyomaviruses (ORs 1.35-1.77). MFIs for anti-WU antibodies were also lower for cases (median 552.6, interquartile range [IQR] 140.3-1298.3) than controls (median 1096.3, IQR 410.3-2044.3; p-value 0.047). The association of anti-WU antibody with NHL was stronger in samples obtained post-diagnosis (OR 0.18, 95% CI 0.07-0.48) than pre-diagnosis (OR 0.66, 95% CI 0.19-2.31; p-heterogeneity=0.037). Conclusion: Our data do not directly implicate known polyomaviruses as lymphomagenic in the setting of HIV-associated immunodeficiency. Nevertheless, impaired antibody response to WU may be a harbinger of AIDS-related lymphoma. Citation Format: Minkyo Song, Noemi Bender, James J. Goedert, Cheryl A. Winkler, Nicole Brenner, Tim Waterboer, Charles S. Rabkin. Associations of polyomavirus seroreactivity with AIDS-related non-Hodgkin's lymphoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 3243.

Impact of CMV PCR Blips in Recipients of Solid Organ and Hematopoietic Stem Cell Transplantation.

Viral blips reflecting polymerase chain reaction (PCR) artefacts or transient low-level replication are well described in the human immunodeficiency virus setting. However, the epidemiology of such blips in transplant recipients screened for cytomegalovirus (CMV) with PCR remains uncertain and was investigated in a cohort of solid organ and hematopoietic stem cell recipients. Eligible recipients had known donor/recipient CMV IgG serostatus, and 3 CMV PCRs ≥. The CMV PCR triplicates (3 consecutive CMV PCRs) were defined; the first CMV PCR was always negative, and the time between the second and third samples was 7 days ≤. A positive second but negative third sample represented a blip. Odds ratio (OR) for factors associated with a triplicate being a blip was estimated by binomial regression adjusted for repeated measurements. Whether blips affected the hazard ratio (HR) for subsequent CMV infection was determined with a Cox model. 851 recipients generated 3883 CMV PCR triplicates. The OR of a triplicate representing a blip decreased with increasing viral load of the second sample (vs 273 IU/mL; >273-910 IU/mL: odds ratio [OR], 0.2; 95% confidence interval [CI], 0.1-0.5; >910 IU/mL: OR, 0.08; 95% CI, 0.02-0.2; P ≤ 0.0002) and increased with intermediary-/low-risk serostatus (vs high risk) (OR, 2.8; 95% CI, 1.2-5.5; P = 0.01). Cumulative exposure to DNAemia in the CMV blips greater than 910 IU/mL indicated increased HR of subsequent CMV infection (HR, 4.6; 95% CI, 1.2-17.2; P = 0.02). Cytomegalovirus blips are frequent; particularly when the viral load of the first positive PCR is < 910 IU/mL, and serostatus risk is intermediary/low. Accumulating blips suggest intermittent low-level replication. If blips are suspected, confirmation of ongoing replication before initiation of treatment is prudent.

Upper and Lower Gastrointestinal Endoscopic Findings in HIV-Infected Patients in the Era of Highly Active Antiretroviral Therapy

BackgroundEndoscopic evaluation with biopsies are instrumental in the diagnosis and management of gastrointestinal (GI) disorders in the setting of human immunodeficiency virus (HIV) or acquired immunodeficiency syndrome (AIDS), especially in the era of highly active antiretroviral therapy (HAART).MethodsA retrospective chart review of 304 HIV-positive and 199 HIV-negative patients who had undergone upper and/or lower endoscopy in an urban community hospital from the years 2012 - 2017 was performed. Inclusion criteria included men and women between the ages of 45 to 75 years, which had undergone colonoscopies between within 2012 - 2017 and had tested positive for HIV. They were selected from that population if they had complete charts that included information regarding symptoms, viral load, cluster of differentiation 4 (CD4) count, prescribed HAART medication, findings from the upper and lower colonoscopy both from the gastroenterologist’s report and pathologist’s report. Only then would they be added to the pool of final selection that we could compute data from and draw conclusions.ResultsAmong HIV patients, those with less than 200 CD4 cells/µL counts had lower rates of diverticulosis and hemorrhoids, as compared with those with greater than 200 cells/µL counts. Other gross and histological findings (from either upper or lower endoscopy) were not statistically different between these two groups. In HIV-positive patients, gastritis, Helicobacter pylori (HP) infection, and esophagitis were significantly less common, while Candida esophagitis was more common. Among HIV patients taking different HAART regimens, the prevalence of peptic ulcers was significantly higher in those taking IIs than that in those who were not.ConclusionsPhysicians should consider the possibility that the GI symptoms in HIV-infected patients on HAART may be due to an opportunistic infection, even when the CD4 count is more than 200 cells/µL and the viral load is low.

Ileo-ileal Intussusception and Bowel Obstruction Caused by Plasmablastic Lymphoma of Small Bowel- A Rare Entity in Rare Location

Intussusception of small bowel is considered a rare cause of bowel obstruction in adults accounting for only about 1% of bowel obstruction in adults. Intussusception in adults is uncommon with 95% cases of intussusceptions occurring in children. Adult intussusception from small intestinal lymphoma is also rare with only 36 cases reported in the literature between 2000 and 2011. Plasmablastic lymphoma (PBL) is an aggressive lymphoid neoplasm usually seen in the oral cavity in the clinical setting of human immunodeficiency virus (HIV) infection. Plasmablastic lymphoma of the small intestine is extremely rare. Here, we report a case of plasmablastic lymphoma of small bowel with ileoileal intussusception in an HIV-negative immunocompetent male patient.

Therapeutics targeting inflammation in the immune reconstitution inflammatory syndrome.

Immune reconstitution inflammatory syndrome (IRIS) is characterized by improvement in a previously incompetent human immune system manifesting as worsening of clinical symptoms secondary to the ability of the immune system to now mount a vigorous inflammatory response. IRIS was first recognized in the setting of human immunodeficiency virus, and this clinical setting continues to be where it is most frequently encountered. Hallmarks of the pathogenesis of IRIS, independent of the clinical presentation and the underlying pathogen, include excessive activation of the immune system, with increased circulating effector memory T cells, and elevated levels of serum cytokines and inflammatory markers. Patients with undiagnosed opportunistic infections remain at risk for unmasking IRIS at the time of active antiretroviral therapy (ART) initiation. Systematic screening for opportunistic infections before starting ART is a key element to prevent this phenomenon. Appropriate management of IRIS requires prompt recognition of the syndrome and exclusion of alternative diagnoses, particularly underlying infections and drug resistance. Controlled studies supporting the use of pharmacologic interventions in IRIS are scare, and recommendations are based on case series and expert opinions. The only controlled trial published to date, showed reduction in morbidity in patients with paradoxical tuberculosis-related IRIS with the use of oral corticosteroids. There are currently limited data to recommend other anti-inflammatory or immunomodulatory therapies that are discussed in this review, and further research is needed. Ongoing research regarding the immune pathogenesis of IRIS will likely direct future rational therapeutic approaches and clinical trials.

Screening to prevent anal cancer: Current thinking and future directions.

Screening to prevent anal cancer: Current thinking and future directions.