Real-World Safety and Effectiveness of Letermovir in Patients Undergoing Allogenic Hematopoietic Stem Cell Transplantation: Final Results of Post-Marketing Surveillance in Japan.

Background And Objective: Cytomegalovirus (CMV) is a common opportunistic infection after allogenic hematopoietic stem cell transplantation (allo-HSCT). Letermovir, an inhibitor of CMV DNA terminase, is approved for CMV prophylaxis in allo-HSCT patients. We report the final results of post-marketing surveillance of letermovir in Japan.

Analyzing Patient-Sharing Network Using an Administrative Claim Database in Japan.

We analyzed the behavior of patient with a focus on patient-sharing based on the methodology of network analysis. We used an administrative healthcare claims database from September of the years 2008-2020 to identify shared patients with hypertension. The patients' behavior of visiting multiple medical facilities was extracted as graphical data, and we calculated density and centrality as indicators to evaluate the structure of the patient sharing network.

Changes in Demand Volume and Patient/Health Care Provider Characteristics of First-Time Telehealth Users: A Comparative Analysis Before and After the COVID-19 Policy Response Using the Administrative Claims Database.

The COVID-19 pandemic has led to a decrease in demand for medical services in Japan, but the utilization of telehealth, which the Japanese government has recently promoted, has seen a temporary increase. This study aims to analyze the trend of telehealth utilization and changes in patient characteristics following the policy response to COVID-19. This retrospective study analyzed data from 26,152 adult patients who used telehealth for the first time between April 2019 and April 2021 in Mie Prefecture, Japan.

Exploring Current Practice, Knowledge, and Challenges of Sexually Transmitted Infection/HIV Management and Pre-Exposure Prophylaxis Among Japanese Health Care Professionals: A Cross-Sectional Web Survey.

We conducted a web-based survey targeting physicians in specialties of treating sexually transmitted infection (STI) and/or human immunodeficiency virus (HIV) patients to understand the current STI/HIV care practices and their acceptability of and barriers to the prescription of pre-exposure prophylaxis (PrEP) in Japan. A descriptive analysis was used to summarize survey responses. Univariate and multivariable logistic regression were performed to identify factors associated with willingness to prescribe PrEP.

The Association Between Telehealth Utilization and Policy Responses on COVID-19 in Japan: Interrupted Time-Series Analysis.

Background: Telehealth using telephones or online communication is being promoted as a policy initiative in several countries. However, there is a lack of research on telehealth utilization in a country such as Japan that offers free access to medical care and regulates telehealth provision-particularly with respect to COVID-19.

Objective: The present study aimed to clarify telehealth utilization, the characteristics of patients and medical institutions using telehealth, and the changes to telehealth in Japan in order to support the formulation of policy strategies for telehealth provision.

Nation-Wide Viral Sequence Analysis of HIV-1 Subtype B Epidemic in 2003-2012 Revealed a Contribution of Men Who Have Sex With Men to the Transmission Cluster Formation and Growth in Japan.

To better understand the epidemiology of human immunodeficiency virus type 1 (HIV-1) subtype B transmission in Japan, phylodynamic analysis of viral sequences was conducted on individuals newly diagnosed as HIV-1 seropositive. A total of 5,018 patients newly diagnosed with HIV-1 infection and registered in the Japanese Drug Resistance HIV Surveillance Network from 2003 to 2012 were enrolled in the analysis. Using the protease-reverse transcriptase nucleotide sequences, their subtypes were determined, and phylogenetic relationships among subtype B sequences were inferred using three different methods: distance-matrix, maximum likelihood, and Bayesian Markov chain Monte Carlo.

Short Communication: HIV-DRLink: A Tool for Reporting Linked HIV-1 Drug Resistance Mutations in Large Single-Genome Data Sets Using the Stanford HIV Database.

The prevalence of HIV-1 drug resistance is increasing worldwide and monitoring its emergence is important for the successful management of populations receiving combination antiretroviral therapy. It is likely that pre-existing drug resistance mutations linked on the same viral genomes are predictive of treatment failure. Because of the large number of sequences generated by ultrasensitive single-genome sequencing (uSGS) and other similar next-generation sequencing methods, it is difficult to assess each sequence individually for linked drug resistance mutations.

Ultrasensitive single-genome sequencing: accurate, targeted, next generation sequencing of HIV-1 RNA.

Background: Although next generation sequencing (NGS) offers the potential for studying virus populations in unprecedented depth, PCR error, amplification bias and recombination during library construction have limited its use to population sequencing and measurements of unlinked allele frequencies. Here we report a method, termed ultrasensitive Single-Genome Sequencing (uSGS), for NGS library construction and analysis that eliminates PCR errors and recombinants, and generates single-genome sequences of the same quality as the "gold-standard" of HIV-1 single-genome sequencing assay but with more than 100-fold greater depth.

Results: Primer ID tagged cDNA was synthesized from mixtures of cloned BH10 wild-type and mutant HIV-1 transcripts containing ten drug resistance mutations.

Unique Flap Conformation in an HIV-1 Protease with High-Level Darunavir Resistance.

Darunavir (DRV) is one of the most powerful protease inhibitors (PIs) for treating human immunodeficiency virus type-1 (HIV-1) infection and presents a high genetic barrier to the generation of resistant viruses. However, DRV-resistant HIV-1 infrequently emerges from viruses exhibiting resistance to other protease inhibitors. To address this resistance, researchers have gathered genetic information on DRV resistance.

Clonally expanded CD4+ T cells can produce infectious HIV-1 in vivo.

Reservoirs of infectious HIV-1 persist despite years of combination antiretroviral therapy and make curing HIV-1 infections a major challenge. Most of the proviral DNA resides in CD4(+)T cells. Some of these CD4(+)T cells are clonally expanded; most of the proviruses are defective.

Quasispecies Analyses of the HIV-1 Near-full-length Genome With Illumina MiSeq.

Human immunodeficiency virus type-1 (HIV-1) exhibits high between-host genetic diversity and within-host heterogeneity, recognized as quasispecies. Because HIV-1 quasispecies fluctuate in terms of multiple factors, such as antiretroviral exposure and host immunity, analyzing the HIV-1 genome is critical for selecting effective antiretroviral therapy and understanding within-host viral coevolution mechanisms. Here, to obtain HIV-1 genome sequence information that includes minority variants, we sought to develop a method for evaluating quasispecies throughout the HIV-1 near-full-length genome using the Illumina MiSeq benchtop deep sequencer.

HIV-1 CRF01_AE and Subtype B Transmission Networks Crossover: A New AE/B Recombinant Identified in Japan.

The major circulating HIV-1 strains in Japan have been subtype B (B) followed by CRF01_AE (AE) in newly diagnosed HIV/AIDS cases. These two subtypes have distinct epidemiological characteristics; B predominates in men who have sex with men, while AE is observed mostly in heterosexuals engaging in high-risk sex. However, transmission networks of these two high-risk populations appear to be crossing over and diffusing.

Characteristics of Transmitted Drug-Resistant HIV-1 in Recently Infected Treatment-Naive Patients in Japan.

Objectives: Progress in antiretroviral treatment has led to fewer virological failure cases, but 10%-20% of treatment-naive HIV/AIDS cases are reported to harbor drug-resistant strains, suggesting transmission of drug-resistant HIV. We aimed to determine the trend in prevalence of transmitted drug-resistant (TDR) HIV in Japan, particularly in recently infected patients.

Methods: Drug-resistance test was performed on 3904 HIV-1-infected cases newly diagnosed between 2007 and 2012.

Longitudinal Detection and Persistence of Minority Drug-Resistant Populations and Their Effect on Salvage Therapy.

Background: Drug-resistant HIV are more prevalent and persist longer than previously demonstrated by bulk sequencing due to the ability to detect low-frequency variants. To clarify a clinical benefit to monitoring minority-level drug resistance populations as a guide to select active drugs for salvage therapy, we retrospectively analyzed the dynamics of low-frequency drug-resistant population in antiretroviral (ARV)-exposed drug resistant individuals.

Materials And Methods: Six HIV-infected individuals treated with ARV for more than five years were analyzed.

Geographic and temporal trends in the molecular epidemiology and genetic mechanisms of transmitted HIV-1 drug resistance: an individual-patient- and sequence-level meta-analysis.

Background: Regional and subtype-specific mutational patterns of HIV-1 transmitted drug resistance (TDR) are essential for informing first-line antiretroviral (ARV) therapy guidelines and designing diagnostic assays for use in regions where standard genotypic resistance testing is not affordable. We sought to understand the molecular epidemiology of TDR and to identify the HIV-1 drug-resistance mutations responsible for TDR in different regions and virus subtypes.

Methods And Findings: We reviewed all GenBank submissions of HIV-1 reverse transcriptase sequences with or without protease and identified 287 studies published between March 1, 2000, and December 31, 2013, with more than 25 recently or chronically infected ARV-naïve individuals.

Contact sensitivity in patients with recalcitrant atopic dermatitis.

Patients with atopic dermatitis are usually responsive to conventional treatment such as topical steroids; however, they are sometimes refractory to the treatment. The influence of contact sensitivities on the course of patients with recalcitrant atopic dermatitis is not known. The aim of this study was to investigate whether contact sensitivities affect the course of patients with recalcitrant atopic dermatitis.

Japanese external quality assessment program to standardize HIV-1 drug-resistance testing (JEQS2010 program) using in vitro transcribed RNA as reference material.

To design appropriate antiretroviral therapy regimens and avoid the emergence of human immunodeficiency virus (HIV)-1 variants with reduced susceptibility to antiretroviral drugs, genotypic drug-resistance testing (HIV genotyping) is strongly recommended. To monitor the quality of HIV genotyping in Japan, we performed an external quality assessment (EQA), named the Japanese external quality assessment program, to standardize HIV genotyping (JEQS). To accurately evaluate the quality of HIV genotyping, we employed as reference material (RM) a well-characterized sample, in vitro transcribed RNA (trRNA) that includes the HIV gag-pol sequence, and created a JEQS2010 panel consisting of three single variant and three mixed trRNA samples.

Phylodynamic analysis reveals CRF01_AE dissemination between Japan and neighboring Asian countries and the role of intravenous drug use in transmission.

Background: One major circulating HIV-1 subtype in Southeast Asian countries is CRF01_AE, but little is known about its epidemiology in Japan. We conducted a molecular phylodynamic study of patients newly diagnosed with CRF01_AE from 2003 to 2010.

Methods: Plasma samples from patients registered in Japanese Drug Resistance HIV-1 Surveillance Network were analyzed for protease-reverse transcriptase sequences; all sequences undergo subtyping and phylogenetic analysis using distance-matrix-based, maximum likelihood and Bayesian coalescent Markov Chain Monte Carlo (MCMC) phylogenetic inferences.

Highly-sensitive allele-specific PCR testing identifies a greater prevalence of transmitted HIV drug resistance in Japan.

Background: The transmission of drug-resistant HIV in newly identified infected populations has become an underlying epidemic which can be better assessed with sensitive resistance testing. Since minority drug resistant variants cannot be detected by bulk sequencing, methods with improved sensitivity are required. Thus, the goal of this study was to evaluate if transmitted drug resistance mutations at minority levels in Japanese patients could be identified using highly sensitive allele-specific PCR (AS-PCR).

Prevalence of transmitted HIV drug resistance in Iran between 2010 and 2011.

Objective: Drug-resistant (DR) HIV emerges during combined antiretroviral treatment (cART), creating concern about widespread transmission of DR-HIV as cART is expanded in resource-limited countries. The aim of this study was to determine the predominant HIV-1 subtypes and prevalence of transmitted DR mutations among antiretroviral-naïve patients in Iran.

Design: To monitor transmission of DR HIV, a threshold surveillance based on the world health organization (WHO) guidelines was implemented in Iran.

Molecular epidemiology of HIV type 1 infection in Iran: genomic evidence of CRF35_AD predominance and CRF01_AE infection among individuals associated with injection drug use.

To understand the molecular epidemiology of HIV-1 infection in Iran, we conducted the first study to analyze the genome sequence of Iranian HIV-1 isolates. For this cross-sectional study, we enrolled 10 HIV-1-infected individuals associated with injection drug use from Tehran, Shiraz, and Kermanshah. Near full-length genome sequences obtained from their plasma samples were used for phylogenetic tree and similarity plotting analyses.

Outbreak of infections by hepatitis B virus genotype A and transmission of genetic drug resistance in patients coinfected with HIV-1 in Japan.

The major routes of hepatitis B virus (HBV) infection in Japan has been mother-to-child transmission (MTCT) and blood transfusion. However, HBV cases transmitted through sexual contact are increasing, especially among HIV-1-seropositive patients. To understand the molecular epidemiology of HBV in HBV/HIV-1 coinfection, we analyzed HBV genotypes and HIV-1 subtypes in HBV/HIV-1-coinfected patients at Nagoya Medical Center from 2003 to 2007.