Mpox in people with HIV: A narrative review.

OBJECTIVE: The 2022 global mpox outbreak disproportionately impacted people living with HIV. This review explores recent evidence on mpox in this group, focusing on clinical presentation, complications, treatment modalities and vaccine strategies. RECENT FINDINGS: Recent studies have suggested that people with HIV diagnosed with mpox have a greater risk of proctitis and hospitalization compared with people without HIV. In addition, those with advanced immunosuppression face an elevated risk of severe mpox infection, which can lead to mortality. Comprehensive and prompt supportive care using antiretrovirals and mpox antivirals is crucial in this group. Although results from randomized clinical trials are still forthcoming, recent studies suggest that early initiation of tecovirimat can prevent disease progression in people with HIV. The non-replicative attenuated smallpox vaccine is well tolerated and effective in preventing monkeypox virus infections in people with HIV. Further studies are needed regarding long-term vaccine effectiveness for this population. CONCLUSION: Evaluating the risk of severe mpox in people living with HIV requires assessing the level of immune suppression and viral control. Universal access to vaccination is imperative to prevent the resurgence of future outbreaks.

Efficacy and viral dynamics of tecovirimat in patients with MPOX: A multicenter open-label, double-arm trial in Japan.

INTRODUCTION: Tecovirimat's application in treating mpox remains under-researched, leaving gaps in clinical and virological understanding. METHODS: The Tecopox study in Japan evaluated the efficacy and safety of tecovirimat in patients with smallpox or mpox, who were divided into oral tecovirimat and control groups. Patients with mpox enrolled between June 28, 2022, and April 30, 2023, were included. Demographic and clinical details along with blood, urine, pharyngeal swab, and skin lesion samples were gathered for viral analysis. A multivariable Tobit regression model was employed to identify factors influencing prolonged viral detection. RESULTS: Nineteen patients were allocated to the tecovirimat group, and no patients were allocated to the control group. The median age was 38.5 years, and all patients were males. Ten patients (52.6%) were infected with human immunodeficiency virus (HIV). Sixteen patients (84.2%) had severe disease. Nine of the 15 patients (60.0%) (four patients withdrew before day 14) had negative PCR results for skin lesion specimens 14 days after inclusion. The mortality rates were 0% on days 14 and 30. No severe adverse events were reported. HIV status and the number of days from symptom onset to tecovirimat administration were associated with lower Ct values (p = 0.027 and p < 0.001, respectively). The median number of days when PCR testing did not detect the mpox virus in each patient was 19.5 days. CONCLUSION: Early tecovirimat administration might reduce viral shedding duration, thereby mitigating infection spread. Moreover, patients infected with HIV showed prolonged viral shedding, increasing the transmission risk compared to those without HIV.

Virological outcomes of various first-line ART regimens in patients harbouring HIV-1 E157Q integrase polymorphism: a multicentre retrospective study.

BACKGROUND: Integrase strand transfer inhibitors (INSTIs) are recommended as first-line ART for people living with HIV (PLWH) in most guidelines. The INSTI-resistance-associated mutation E157Q, a highly prevalent (2%-5%) polymorphism of the HIV-1 (human immunodeficiency virus type 1) integrase gene, has limited data on optimal first-line ART regimens. We assessed the virological outcomes of various first-line ART regimens in PLWH with E157Q in real-world settings. METHODS: A multicentre retrospective observational study was conducted on PLWH who underwent integrase genotypic drug-resistance testing before ART initiation between 2008 and 2019 and were found to have E157Q. Viral suppression (<50 copies/mL) rate at 24 and 48 weeks, time to viral suppression and time to viral rebound (≥100 copies/mL) were compared among the first-line ART regimens. RESULTS: E157Q was detected in 167 (4.1%) of 4043 ART-naïve PLWH. Among them, 144 had available clinical data after ART initiation with a median follow-up of 1888 days. Forty-five started protease inhibitors + 2 NRTIs (PI group), 33 started first-generation INSTI (raltegravir or elvitegravir/cobicistat) + 2 NRTIs (INSTI-1 group), 58 started once-daily second-generation INSTI (dolutegravir or bictegravir) + 2 NRTIs (INSTI-2 group) and eight started other regimens. In the multivariate analysis, the INSTI-2 group showed similar or favourable outcomes compared with the PI group for viral suppression rates, time to viral suppression and time to viral rebound. Two cases in the INSTI-1 group experienced virological failure. CONCLUSIONS: The general guideline recommendation of second-generation INSTI-based first-line ART for most PLWH is also applicable to PLWH harbouring E157Q.

Late diagnosis of HIV in 2022: Why so little change?

BACKGROUND: The proportion of people who are diagnosed late is a key metric to measure the public health response to HIV. But this percentage remains stubbornly high in nearly every country. Delays in accessing antiretroviral therapy affects both (i) individual health, due to a higher risk of mortality, and (ii) population-based health, due to continued risk of transmission. Despite huge efforts to increase testing, late diagnosis continues to be an indication of a public health failure. OUTLINE: This short review includes community perspectives on why late diagnosis continues and how it may be reduced. We discuss both structural barriers that prevent people from testing earlier and personal reasons why some people still refuse testing when offered. We note that late diagnosis is reported in all countries and in all demographic groups and that sex, gender, age, and sexuality all affect these rates. However, even in groups with high HIV awareness, such as in gay and bisexual men in the UK, more than one in three people with HIV continue to be diagnosed late. Fears and prejudice about HIV based on outdated information are still common among both health workers and people using health services. For example, testing is still not offered in primary or emergency care settings, and even free testing might not be accepted if someone fears the outcome might jeopardize their resident status, employment, relationship, or health. SUMMARY: In addition to developing targeted projects to reach the highest-risk groups, a positive mainstream public campaign could make testing more acceptable at a broad population level across all demographics. This could challenge and repair the media campaigns from the 1980s that still contribute to the stigma that frightens people away from testing now. We hope that an effective approach in one country might also help others.

Meningococcal pneumonia in Japan: A case report and literature review.

Neisseria meningitidis often causes meningitis and meningococcemia; however, meningococcal pneumonia is quite rare. Herein, we report a case of non-invasive meningococcal pneumonia initially misdiagnosed as pneumonia due to Moraxella catarrhalis on the basis of a Gram stain in a 43-year-old woman with asthma, type 2 diabetes mellitus, and schizophrenia. She visited our hospital following a 3-day history of fever, productive cough, and shortness of breath. Since her sputum smear revealed Gram-negative diplococcus and the chest radiograph showed infiltration in the lower right lung field, her initial diagnosis was pneumonia caused by M. catarrhalis. However, the next day, the sputum culture colonies were unlike those of M. catarrhalis, and matrix-assisted laser desorption/ionization time of flight mass spectrometry analysis revealed the pathogen to be N. meningitidis. As a result, we administered the appropriate treatment and ensured adequate infection prevention and control measures including, droplet precautions and prophylaxis provided to close contacts. Secondary infection did not occur. Although meningococcal pneumonia is not common, physicians should consider N. meningitidis when Gram-negative diplococci are observed in respiratory specimens, as N. meningitidis cannot be distinguished from M. catarrhalis with Gram staining alone. Moreover, it is also important to monitor the appearance of the pathogenic colonies and to closely coordinate with laboratory technicians to determine appropriate treatments. In this article, we review the previous case reports of meningococcal pneumonia reported in 1984-2015 in Japan, summarizing the clinical characteristics and comparing previous reviews of the literature.

The prevalence of airway obstruction among Japanese HIV-positive male patients compared with general population; a case-control study of single center analysis.

BACKGROUND AND OBJECTIVE: Previous studies have suggested that human immunodeficiency virus (HIV) infection and/or the airway colonization of Pneumocystis jirovecii (Pcj) impact on the progression of airway obstruction, such as chronic obstructive pulmonary disease (COPD). This study was aimed to evaluate the relationship between HIV infection, airway colonization of Pcj and airway obstruction in Japanese male patients. METHODS: Case-control study of 49 HIV-positive and 257 HIV-negative men were enrolled in this study. Airway obstruction was determined by spirometry. Cigarette smoking was determined by a self report. Laboratory data were obtained from medical records. Among HIV positive patients, the airway colonization of Pcj was evaluated by induced sputum using the real time polymerase chain reaction method. RESULTS: Forty-eight out of 49 (97.9%) HIV-positive patients received antiretroviral therapy, and their median CD4 cell counts were 491/µL (79-935). The prevalence of airway obstruction as determined by spirometry was 10.2% (5/49) in HIV-positive subjects and 2.4% (5/208) in HIV-negative subjects (p = 0.024). Compared with the control group, HIV-positive patients were significantly younger (median age 44 vs 40, p = 0.019). After adjusting for age, pack-years of smoking, HIV infection was an independent risk factor for airway obstruction (OR; 10.93, 95%CI 1.99-60.1, p = 0.006). None of patient was detected the airway colonization of Pcj. CONCLUSIONS: HIV infection was an independent risk factor for airway obstruction regardless of airway colonization of Pcj. Health-care providers should be aware of the increased likelihood of airway obstruction among HIV-positive patients.

Are MMSE and HDS-R neuropsychological tests adequate for screening HIV-associated neurocognitive disorders?

HIV-associated neurocognitive disorders (HAND) are one of major comorbidities in patients with HIV-1 infection. There are currently no standardized tests for screening HAND in such patients. The sensitivity of the cognitive function tests routinely used in clinical practice, such as the Mini-Mental State Examination and the Revised Hasegawa's Dementia Scale, is inadequate to rule out HAND, even in patients with clear abnormal behavior. We report a 41-year-old man with HIV-associated dementia, the most severe form of HAND, in whom the simplified methods did not show abnormal results, and a comprehensive battery of neuropsychological tests which covering several cognitive domains was needed to detect cognitive impairment.

Association of demographics, HCV co-infection, HIV-1 subtypes and genetic clustering with late HIV diagnosis: a retrospective analysis from the Japanese Drug Resistance HIV-1 Surveillance Network.

INTRODUCTION: Late diagnosis of the human immunodeficiency virus (HIV) is a major concern epidemiologically, socially and for national healthcare systems. Although the association of certain demographics with late HIV diagnosis has been reported in several studies, the association of other factors, including clinical and phylogenetic factors, remains unclear. In the present study, we conducted a nationwide analysis to explore the association of demographics, clinical factors, HIV-1 subtypes/circulating recombinant form (CRFs) and genetic clustering with late HIV diagnosis in Japan, where new infections mainly occur among young men who have sex with men (MSM) in urban areas. METHODS: Anonymized data on demographics, clinical factors and HIV genetic sequences from 39.8% of people newly diagnosed with HIV in Japan were collected by the Japanese Drug Resistance HIV-1 Surveillance Network from 2003 to 2019. Factors associated with late HIV diagnosis (defined as HIV diagnosis with a CD4 count <350 cells/µl) were identified using logistic regression. Clusters were identified by HIV-TRACE with a genetic distance threshold of 1.5%. RESULTS: Of the 9422 people newly diagnosed with HIV enrolled in the surveillance network between 2003 and 2019, 7752 individuals with available CD4 count at diagnosis were included. Late HIV diagnosis was observed in 5522 (71.2%) participants. The overall median CD4 count at diagnosis was 221 (IQR: 62-373) cells/µl. Variables independently associated with late HIV diagnosis included age (adjusted odds ratio [aOR] 2.21, 95% CI 1.88-2.59, ≥45 vs. ≤29 years), heterosexual transmission (aOR 1.34, 95% CI 1.11-1.62, vs. MSM), living outside of Tokyo (aOR 1.18, 95% CI 1.05-1.32), hepatitis C virus (HCV) co-infection (aOR 1.42, 95% CI 1.01-1.98) and not belonging to a cluster (aOR 1.30, 95% CI 1.12-1.51). CRF07_BC (aOR 0.34, 95% CI 0.18-0.65, vs. subtype B) was negatively associated with late HIV diagnosis. CONCLUSIONS: In addition to demographic factors, HCV co-infection, HIV-1 subtypes/CRFs and not belonging to a cluster were independently associated with late HIV diagnosis in Japan. These results imply the need for public health programmes aimed at the general population, including but not limited to key populations, to encourage HIV testing.

[Clinical features of diabetic patients with pulmonary tuberculosis admitted to a university hospital].

Diabetes mellitus (DM) is a risk factor of tuberculosis (TB). We studied the clinical presentation of pulmonary TB among patients with DM in comparison with patients without DM who were admitted into the hospital of the University of the Ryukyus from 2006 to 2010. The clinical data were collected from medical records retrospectively. Ten cases (25%) of hospitalized patients with pulmonary TB had DM. The DM group showed lower Body Mass Index and higher incidence of chronic heart failure and chronic renal failure. The DM group also were more likely to have cavitary lesion, had longer period of hospitalization, and higher mortality. Their causes of deaths were mainly the co-morbidities and associated complications. Further studies are warranted in order to fully elucidate the relationships between pulmonary TB and DM.

Mechanisms involved in the extension of pulmonary Mycobacterium avium infection from the pulmonary focus to the regional lymph nodes.

PURPOSE: This study was designed to evaluate the mechanism of Mycobacterium avium extension in lung infection. STUDY DESIGN: Retrospective study. PARTICIPANTS: A 42-year-old man with acquired immune deficiency syndrome and immune reconstitution inflammatory syndrome. The patient developed mediastinal lymphadenopathy and a peripheral lesion in the right upper lobe within 2 weeks of starting highly active antiretroviral therapy. METHODS: Pulmonary tissue and lymph nodes were dissected under thoracoscopy and evaluated pathologically and immunohistochemically. RESULTS: Pulmonary pathologic examination revealed extensive granuloma formation throughout the acini. Mycobacterial antigens were found in the macrophages in the alveoli and in the alveolar septa. Some macrophages including mycobacterial antigens were surrounded by lymphatic endothelial cells in the interstitium. In addition, a proliferative granulomatous lesion was found under the intact epithelial layer of a bronchiole. Pathological examination of the lymph nodes revealed aggregated proliferative granulomas with few mycobacteria. Genetically closely related M. avium strains were isolated from both tissues. CONCLUSIONS: This study showed the mechanism involved in the progression of pulmonary M. avium infection from the pulmonary focus to the regional lymph nodes via the lymphatic vessels.

[Comparison of pneumonia severity indices between modified A-DROP system and current A-DROP system predicting outcomes for patients hospitalized with community-acquired pneumonia].

BACKGROUND: The A-DROP is a predicting pneumonia severity index which is adopted in the Japanese Respiratory Society (JRS) guidelines. For community-acquired pneumonia, we made a modified A-DROP, adding two new index items to the current A-DROP. Then, we retrospectively compared the modified A-DROP with the current A-DROP regarding 30-day mortality. METHODS AND RESULTS: We analyzed consecutive 227 patients hospitalized with community-acquired pneumonia (mean age 79.0 years). The added index items were respiratory rate > or = 30/min and the presence or absence of underlying diseases. There were 16 fatalities (7.0%). In the extremely severe group, the sensitivities of the 30-day death and odds ratios were 19.9% and 9.5 in the current A-DROP, but 75.0% and 14.1 for the modified A-DROP, respectively. In addition, regarding the receiver-operating characteristic (ROC) area under the curve for the 30-day death ratio, the current A-DROP and modified A-DROP were 0.807 and 0.840, respectively. CONCLUSIONS: The modified A-DROP improved the ability to predict outcomes compared with the current A-DROP.

Case Report: Iliopsoas Hematoma during the Clinical Course of Severe COVID-19 in Two Male Patients.

Anticoagulation plays a major role in reducing the risk of systematic thrombosis in patients with severe COVID-19. Serious hemorrhagic complications, such as intracranial hemorrhage, have also been recognized. However, intra-abdominal hemorrhage is under-recognized because of its rare occurrence, despite high mortality. Here, we discuss two cases of spontaneous iliopsoas hematoma (IPH) likely caused by anticoagulants during the clinical course of COVID-19. We also explored published case reports to identify clinical characteristics of IPH in COVID-19 patients. The use of anticoagulants may increase the risk of lethal IPH among COVID-19 patients becsuse of scarce data on optimal dosage and adequate monitoring of anticoagulant effects. Rapid diagnosis and timely intervention are crucial to ensure good patient outcomes.

Case Report: Ischemic Enterocolitis Associated with Coronavirus Disease 2019: Two Case Reports and a Review of the Literature.

The COVID-19 pandemic has caused serious health and social concerns worldwide. Although the primary target of SARS-CoV-2 is the respiratory tract, SARS-CoV-2 infection also causes extrapulmonary symptoms. Previous articles have reported ischemic colitis in COVID-19 patients; however, information regarding its clinical manifestations and pathophysiology is limited. In this case report, we present two cases of ischemic enterocolitis in COVID-19 patients and review past case reports. Our literature review has shown that computed tomography rather than endoscopy was used for the diagnosis, and any region of the intestine was affected. Because the elevation of the D-dimer, which suggested a hypercoagulable state, was reported in most cases, we assumed that thrombosis at any level in the artery and vein was involved in the pathophysiology of COVID-19-associated enterocolitis. SARS-CoV-2-induced endotheliitis can cause both coarctation of the vessels and thrombosis; therefore, both patterns of ischemic colitis, occlusive and nonocclusive, may be involved in COVID-19-associated enterocolitis.

[Secondary organizing pneumonia after pneumococcal pneumonia].

A 28-year-old woman was admitted to our hospital complaining of a 7-day chilly sensation with fever. She was given a diagnosis of pneumococcal pneumonia because of infiltration on chest radiography, sputum gram staining and testing positive for a pneumococcal urinary antigen. A 10-day course of antibiotics showed improvements in symptoms and infiltration. However, her X-ray film revealed severe volume loss in the right lung. Organizing pneumonia was diagnosed with lymphocytosis in BALF and Masson bodies upon TBLB examination. Administration of prednisolone obtained rapid improvement of the volume loss. This case was interesting, showing an organizing tendency in the acute-stage pneumococcal pneumonia.

Seizure followed by lung edema: An intriguing link between the brain and the lung.

When observing diffuse ground-glass opacities in both lungs, physicians should consider several diseases, including heart failure, interstitial lung diseases, and pulmonary infections. However, brain diseases rarely cause lung infiltration. We present an instructive case of neurologic pulmonary edema showing a pathological link between the brain and the lung.

Acute Hypertriglyceridaemia Caused by Tocilizumab in a Patient with Severe COVID-19.

Treatment with tocilizumab (TCZ) to block interleukin-6 (IL-6) signalling is predicted to mitigate cytokine release syndrome (CRS) caused by coronavirus disease 2019 (COVID-19). However, the adverse effects of TCZ on patients with COVID-19 remain unclear. We herein report a patient with COVID-19 treated with TCZ who developed acute hypertriglyceridaemia. Despite favipiravir treatment, acute respiratory distress syndrome developed in a 45-year-old patient with COVID-19; thus, TCZ was initiated. The triglyceride levels greatly increased after TCZ administration. Physicians should consider the negative impact of TCZ on the lipid profile in patients with COVID-19, although COVID-19-induced CRS itself may be an aggravating factor.

Human immunodeficiency virus-associated pulmonary sarcoidosis in a Japanese man as a manifestation of immune reconstitution inflammatory syndrome.

Asymptomatic pulmonary sarcoidosis can develop after starting antiretroviral therapy. The decision on whether to treat sarcoidosis with corticosteroids should be based on the disease severity.

Use of steroids to treat anti-tumor necrosis factor α induced tuberculosis-associated immune reconstitution inflammatory syndrome: Case report and literature review.

INTRODUCTION: Individuals with tuberculosis (TB) who are being treated with anti-tumor necrosis factor α (anti-TNFα) for coexisting conditions may experience unexpected exacerbations of TB after the initiation of antituberculous therapy, so-called anti-TNFα-induced TB-immune reconstitution inflammatory syndrome (anti-TNFα-induced TB-IRIS). Anti-TNFα-induced TB-IRIS is often treated empirically with corticosteroids; however, the evidence of the effectiveness of corticosteroids is lacking and the management can be a challenge. PATIENT CONCERNS: A 32-year-old man on long-term infliximab therapy for Crohn disease visited a clinic complaining of persistent fever and cough that had started 1 week previously. His most recent infliximab injection had been administered 14 days before the visit. A chest X-ray revealed a left pleural effusion, and he was admitted to a local hospital. DIAGNOSIS: A chest computed tomography (CT) scan revealed miliary pulmonary nodules; acid-fast bacilli were found in a sputum smear and a urine sediment sample; and polymerase chain reaction confirmed the presence of Mycobacterium tuberculosis in both his sputum and the pleural effusion. He was diagnosed with miliary TB. INTERVENTIONS: Antituberculous therapy was started and he was transferred to our hospital for further management. His symptoms initially improved after the initiation of antituberculous therapy, but 2 weeks later, his symptoms recurred and shadows on chest X-ray worsened. A repeat chest CT scan revealed enlarged miliary pulmonary nodules, extensive ground-glass opacities, and an increased volume of his pleural effusion. This paradoxical exacerbation was diagnosed as TB-IRIS associated with infliximab. A moderate-dose of systemic corticosteroid was initiated [prednisolone 25 mg/day (0.5 mg/kg/day)]. OUTCOMES: After starting corticosteroid treatment, his radiological findings improved immediately, and his fever and cough disappeared within a few days. After discharge, prednisolone was tapered off over the course of 10 weeks, and he completed a 9-month course of antituberculous therapy uneventfully. He had not restarted infliximab at his most recent follow-up 14 months later. CONCLUSION: We successfully managed a patient with anti-TNFα-induced TB-IRIS using moderate-dose corticosteroids. Due to the limited evidence currently available, physicians should consider the necessity, dosage, and duration of corticosteroids for each case of anti-TNFα-induced TB-IRIS on an individual patient-by-patient basis.