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.

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.

Effect of voluntary human mobility restrictions on vector-borne diseases during the COVID-19 pandemic in Japan: A descriptive epidemiological study using a national database (2016 to 2021).

The coronavirus disease 2019 (COVID-19) pandemic not only encouraged people to practice good hygiene but also caused behavioral inhibitions and resulted reduction in both endemic and imported infectious diseases. However, the changing patterns of vector-borne diseases under human mobility restrictions remain unclear. Hence, we aimed to investigate the impact of transborder and local mobility restrictions on vector-borne diseases through a descriptive epidemiological study. The analysis was conducted using data from the National Epidemiological Surveillance of Infectious Diseases system in Japan. We defined the pre-pandemic period as the period between the 1st week of 2016 to the 52nd week of 2019 and defined the pandemic period as from the 1st week of 2020 to the 52nd week of 2021, with the assumption that human mobility was limited throughout the pandemic period. This study addressed 24 diseases among notifiable vector borne diseases. Datasets were obtained from weekly reports from the National Epidemiological Surveillance of Infectious Diseases, and the incidence of each vector-borne disease was examined. Interrupted time series analysis was conducted on the epidemic curves for the two periods. Between the pre- and post-pandemic periods, the incidence of dengue fever and malaria significantly decreased, which may be related to limited human transboundary mobility (p = 0.003/0.002). The incidence of severe fever with thrombocytopenia syndrome, scrub typhus, and Japanese spotted fever did not show changes between the two periods or no association with human mobility. This study suggests that behavioral control may reduce the incidence of new mosquito-borne diseases from endemic areas but may not affect tick-borne disease epidemics within an endemic area.

Incidence of common infectious diseases in Japan during the COVID-19 pandemic.

Recent reports indicate that respiratory infectious diseases were suppressed during the novel coronavirus disease-2019 (COVID-19) pandemic. COVID-19 led to behavioral changes aimed to control droplet transmission or contact transmission. In this study, we examined the incidence of common infectious diseases in Japan during the COVID-19 pandemic. COVID-19 data were extracted from the national data based on the National Epidemiological Surveillance of Infectious Diseases (NESID). Common infectious diseases were selected from notifiable infectious diseases under the NESID. The epidemic activity of the diseases during 2015-2020 was evaluated based on the Infectious Disease Weekly Reports published by the National Institute of Infectious Diseases. Each disease was then categorized according to the route of transmission. Many Japanese people had adopted hygienic activities, such as wearing masks and hand washing, even before the COVID-19 pandemic. We examined the correlation between the time-series of disease counts of common infectious diseases and COVID-19 over time using cross-correlation analysis. The weekly number of cases of measles, rotavirus, and several infections transmitted by droplet spread, was negatively correlated with the weekly number of cases of COVID-19 for up to 20 weeks in the past. According to the difference-in-differences analysis, the activity of influenza and rubella was significantly lower starting from the second week in 2020 than that in 2015-2019. Only legionellosis was more frequent throughout the year than in 2015-2019. Lower activity was also observed in some contact transmitted, airborne-transmitted, and fecal-oral transmitted diseases. However, carbapenem-resistant Enterobacteriaceae, exanthema subitum, showed the same trend as that over the previous 5 years. In conclusion, our study shows that public health interventions for the COVID-19 pandemic may have effectively prevented the transmission of most droplet-transmitted diseases and those transmitted through other routes.

Clinical and bacterial features of Group B streptococci with reduced penicillin susceptibility from respiratory specimens: a case-control study.

Streptococcus agalactiae (Group B Streptococcus, GBS) is an invasive pathogen that causes sepsis and meningitis among infants, elderly adults, and immunosuppressed patients. Generally, GBS is susceptible to penicillin; however, GBS with reduced penicillin susceptibility (PRGBS) has been reported. PRGBS are commonly isolated from respiratory specimens, but clinical features of patients with PRGBS remain unclear. In this case-control study, clinical features of patients with PRGBS and bacterial characteristics of these isolates from respiratory specimens were investigated. Patients with GBS at the University of the Ryukyus Hospital between January 2017 and June 2018 were retrospectively investigated. GBS were further classified into penicillin-susceptible GBS (PSGBS) and PRGBS using a drug susceptibility test. Moreover, serotypes, genotypes, and drug resistance genes of PRGBS isolates were determined. In total, 362 GBS were isolated, of which 46 were collected from respiratory specimens, which had the highest rate of PRGBS (24%). Compared to patients with PSGBS, those with PRGBS were more likely to have neuromuscular disease, poor performance status, risk of multidrug-resistant pathogen infection, prior pneumonia history within 1 year, and prior penicillin use within 1 year. Among eight PRGBS isolates, multilocus sequence typing revealed that five isolates were sequence type (ST) 358, two were ST3 and ST10, respectively, and one isolate was ST1404. All PRGBS isolates belonged to the ST1/ST19/ST10 group. This study reveals clinical characteristics of patients with PRGBS from respiratory specimens. Because invasive GBS infection cases are increasing, especially in the elderly, more attention should be paid to this infection.

Revised hospital antibiotic formulary reduces antimicrobial consumption and promotes a shift towards narrow-spectrum antibiotic usage.

BACKGROUND: In Japan, the national action plan to adress antimicrobial resistance problems aimed to reduce the use of oral cephalosporins, quinolones, and macrolides per day per 1000 inhabitants by 50% from the levelin 2013 by 2020. The aim of this study was to evaluate the effects of a revised antibiotic formulary on in- and out-hospital oral antibiotic prescribing practices at a 600-bed university hospital. METHOD: A retrospective before-and-after comparison study was conducted. All antimicrobial consumption data in the reviewed classes from 1 January 2013 to 31 December 2018, were extracted from the hospital database's electronic medical records. The data were measured in the defined daily dose and antibiotic use density (defined daily dose per 1000 patient-days). RESULTS: The total oral antibiotic use densities for in-hospital prescriptions in 2013 and 2018 were 117.95 and 75.42, respectively, and 239.83 and 193.88, respectively, for out-hospital prescriptions. From 2013 to 2018, antibiotic use densities of second- and third-generation cephalosporins, macrolides and fluoroquinolones for in-hospital prescriptions changed annually by -49.00%, -92.67%, +0.49% and -48.19%, and out-hospital prescriptions of these antibiotics changed by +76.69%, -86.37%, -16.29% and -51.75%, over the same period. Penicillin prescriptions increased by 71.31% for in-hospital and 42.72% for out-hospital prescriptions over this period. CONCLUSIONS: The revised hospital antibiotic formulary reduced total antibiotic consumption and increased the use of narrow-spectrum antibiotics for both in- and out-hospital prescriptions.

False-positive for SARS-CoV-2 antigen test in a man with acute HIV infection.

Although rapid antigen tests for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is convenient, some articles have demonstrated their low sensitivity indicating false-negative results should always be considered. Here, we raise the issue of false-positive on rapid antigen tests for SARS-CoV-2 with the first case of acute HIV infection who repeatedly positive for the rapid antigen test. A 39-year-old man was admitted to our hospital complaining of high-grade fever, dry cough, general fatigue, and anorexia. The rapid antigen test performed on a nasopharyngeal swab sample was positive, therefore the patient was separated in an isolated room apart from the COVID-19 ward while awaiting the confirmatory RT-PCR result. However, the RT-PCR for SARS-CoV-2 performed on nasopharyngeal swabs was repeatedly negative (three times), while the antigen test was repeatedly positive (three times in total). This patient was eventually diagnosed with acute human immunodeficiency virus (HIV) infection based on a high titer of HIV-RNA and absence of plasma HIV-1/2 antibodies. Physicians should consider the possibility of false-positive results in addition to false-negative results when using a rapid antigen test for SARS-CoV-2, and keep in mind that nucleic acid amplification tests are needed to confirm the diagnosis.

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.

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.

Correlates of lifetime and past one-year HIV-testing experience among men who have sex with men in Japan.

This study aimed to examine correlates of lifetime and past-year HIV testing among men who have sex with men (MSM) in Japan. A unique, anonymous online self-report survey was conducted in 2015. A total of 776 participants completed the survey and answered questions on sociodemographic information, HIV-testing experience, history of syphilis, experience talking about HIV, recognition of AIDS-related community-based organization (CBO) materials, and sex behaviors. HIV-testing experience and related factors were assessed for two groups: regional cities and Tokyo and Osaka. A Poisson regression analysis revealed that higher lifetime HIV testing was associated with older age, previous syphilis diagnosis, and experience talking about HIV. Moreover, higher HIV testing in the past year was associated with experience talking about HIV with friends and recognition of HIV-related CBO materials. Increased dissemination of HIV-related information provided by CBOs may, therefore, be an effective prevention policy intervention targeted at Japanese MSM to promote regular testing and maintain their interest in HIV issues.

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.

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.

Comparison of two screening tests for HIV-Associated Neurocognitive Disorder suspected Japanese patients with respect to cART usage.

In this study, we demonstrated the pervasiveness of HIV-associated neurocognitive disorders (HAND) among a selection of Japanese patients as well as evaluated and compared the Mini Mental State Examination (MMSE) and the International HIV Dementia Scale (IHDS) for use as a screening tool among combination anti-retroviral therapy (cART)-naïve and cART experienced patients. The MMSE and the IHDS have both been used as HAND screening tests around the world with variable success. It has been reported the increased usage of cART the utility of these screening tests may have been diminished due to the decreased severity of impairment and the altered pattern of neurocognitive impairments in cART era HAND patients. It is therefore possible the MMSE and the IHDS may still be useful among cART-naïve patients even in the cART era. However, only one study has investigated and compared the screening results of the IHDS among cART-naïve and cART experienced patients. All HIV positive patients who visited, or were admitted, to the Ryukyu University Hospital between January 2009 and March 2014 were evaluated for inclusion. Selected patients (n = 49) had data without omission for all tests. The overall prevalence of HAND in our cohort was 44%. The area under the curve (AUC), for all subjects using the MMSE and the IHDS, were 0.60 and 0.69, respectively. However, the AUC among cART-naïve patients were 0.58 and 0.76 for the MMSE and the IHDS, respectively. Whereas, cART experienced patients had an AUC of 0.60 and 0.61, respectively. Overall, the MMSE demonstrated a poor screening ability for HAND, regardless of cART usage (the cut-off value of 27 had a Youden's J-Index of 0.1, in all groups). Alternatively, the IHDS was moderately useful for HAND screening among cART-naïve patients (the cut-off value of 11 had a Youden's J-Index of 0.4), but performed poorly as a screening test among cART experienced patients (the cut-off value of 11 had a Youden's J-Index of 0.1).

Clinical Features of Human Metapneumovirus Pneumonia in Non-Immunocompromised Patients: An Investigation of Three Long-Term Care Facility Outbreaks.

Background: Several studies have reported outbreaks due to human metapneumovirus (hMPV) in long-term care facilities (LTCF) for the elderly. However, most of these reports are epidemiological studies and do not investigate the clinical features of hMPV pneumonia. Methods: Three independent outbreaks of hMPV occurred at separate LTCF for intellectually challenged and elderly residents. A retrospective evaluation of hMPV pneumonia and its clinical and radiological features was conducted using available medical records and data. Results: In 105 hMPV infections, 49% of patients developed pneumonia. The median age of pneumonia cases was significantly higher than non-pneumonia cases (P < .001). Clinical manifestations of hMPV pneumonia included high fever, wheezing in 43%, and respiratory failure in 31% of patients. An elevated number of white blood cells as well as increased levels of C-reactive protein, creatine phosphokinase, and both aspartate and alanine transaminases was also observed among pneumonia cases. Evaluation of chest imaging revealed proximal bronchial wall thickenings radiating outward from the hilum in most patients. Conclusions: The aforementioned characteristics should be considered as representative of hMPV pneumonia. Patients presenting with these features should have laboratory testing performed for prompt diagnosis.

Do infections with disseminated Mycobacterium avium complex precede sweet's syndrome? A case report and literature review.

Sweet's syndrome is reportedly associated with preceding nontuberculous mycobacterial infections (NTMIs). Here, we report on a systemic Mycobacterium intracellulare infection in a patient on corticoid therapy for Sweet's syndrome. Literature searches show that 69.1% of patients with Sweet's syndrome and NTMIs developed this syndrome later than NTMIs and 89.3% of them developed during the clinical course of a rapidly growing mycobacterial infection. The residual cases were associated with slow-growing mycobacteria (14.3%), but only three cases of Mycobacterium avium complex (MAC) infections before the onset of Sweet's syndrome have been reported, and all of them were caused by disseminated MAC disease. One of these cases developed during corticoid therapy for Sweet's syndrome, while another case had underlying diabetes mellitus. Hence, the occurrence of systemic MAC disease may be an inevitable consequence of long-term steroid use and underlying diseases. Literature searches also show that cervical lymphadenitis was a predominant symptom in NTMIs (90.5%). The present case did not have cervical lymphadenitis although the previously reported MAC cases did experience it. Therefore, lymphadenitis from NTMIs may be related to the pathogenesis of Sweet's syndrome. Hence, should a patient have systemic infection without lymphadenitis, it will be more difficult to clinically confirm that MAC disease is a predisposing factor for Sweet's syndrome.

Evaluation of Anyplex™ II RV16 and RB5 real-time RT-PCR compared to Seeplex® RV15 OneStep ACE and PneumoBacter ACE for the simultaneous detection of upper respiratory pathogens.

This prospective study was performed to evaluate and compare the performance of the multiplex PCR Seeplex® assays and Anyplex™ II assays. From May 2014 until April 2016, a total of 247 respiratory samples were collected in Okinawa, Japan. Multiple respiratory pathogens were detected in 37% of patients with positive results. The most prevalent pathogens were influenza A virus and respiratory syncytial virus B. Despite minor differences in capabilities, both the Seeplex® assays and Anyplex™ II assays can be easily implemented in diagnostic or research laboratories to optimize the detection and management of respiratory pathogen induced diseases.