Global health & medicine最新文献

Since the world's first case series of human immunodeficiency virus (HIV) infection were reported, more than 40 decades have passed. The advancement of HIV treatment and prevention has progressed drastically. Especially, the efficacy of pre-exposure prophylaxis (PrEP) for HIV prevention has been proven by a number of trials and the number of new HIV cases has declined over the years due to the large-scale and rapid implementation of PrEP and universal HIV treatment in multiple countries. However, in Japan, PrEP is not approved or officially supported as of June 2024. Despite of the absence of top-down movement, men who have sex with men (MSM)-friendly private clinics initiated prescriptions of generic medicines for oral PrEP with necessary tests in Tokyo, which greatly contributed to improve access to PrEP. It is of note that current situation of bottom-up PrEP implementation using generic medicines in Tokyo is obviously cost-saving, which is needless to evaluate. However, expense of PrEP is fully out-of-pocket, which will hinder those with low or no income from accessing PrEP services despite the low prices of generic medicines. Furthermore, current PrEP implementation based on user-friendly clinics is functioning only in Tokyo. The role of public health authorities is important to solve these financial and geographical disparities in accessing PrEP services, without impairing existing virtues of accessibility and cost-saving in the current system.

Human immunodeficiency virus (HIV) impacts millions of individuals worldwide, and well over 2/3 of those living with HIV are accessing antiviral therapies that are successfully repressing viral replication. Most often, HIV treatments and prevention are administered in the form of daily pills as combinations of multiple drugs. An emergent and effective strategy for suppressing viral replication is the application of long-acting antiretroviral therapy (LAART), or antivirals that require less-frequent, non-daily doses. Thus far, the repertoire of LAARTs includes the widely used antiviral classes of non-nucleoside reverse transcriptase inhibitors (NNRTIs) and integrase strand transfer inhibitors (INSTIs) and has recently expanded to include a capsid-targeting antiviral. Possible future additions are nucleoside reverse transcriptase inhibitors (NRTIs) and nucleoside reverse transcriptase translocation inhibitors (NRTTIs). Here, we discuss the different strategies of using long-acting compounds to treat or prevent HIV-1 infection by targeting reverse transcriptase, integrase, and capsid.

Since 2017, China has started a pilot exploration of pre-exposure prophylaxis (PrEP)/post-exposure prophylaxis (PEP) service aiming for human immunodeficiency virus (HIV) control. Efforts to summarize the pilot experience and sort out the gaps in service provision must be prioritized. In June-October, 2023, three provincial capital cities with two years of PrEP/PEP pilot experience in eastern, central and western China were chosen. A structural information collective tool was developed, as a framework to identify key links and steps in reviewing service procedures for PrEP/PEP service. Two main service models have been formed, including the independent offline service model led by professional health institutions and Multi-agencies (health institution/Community Based Organizations (CBOs)/Internet platform) online and offline collaborative service model. The pilot experience conceptualizes opportunities to integrate PrEP/PEP into HIV prevention efforts and, illustrates the optimizing path to move forward to reach for a high level HIV prevention and care continuum. Systematic barriers during the process of integration need to be noted and addressed. It is urgent to establish a realistic and feasible online and offline monitoring system to achieve a balance between standardized, safe, simplified and convenient services.

Primary care and sexual health services for transgender people in Japan are lacking. We surveyed 233 transgender patients (57 [24.5%] assigned male at birth [AMABs] and 176 [75.5%] assigned female at birth [AFABs]) at the Personal Health Clinic to collect data on sexually transmitted infections (STI) and human immunodeficiency virus (HIV) risk, as well as lifestyle, stigma, and health literacy. Among respondents, 55% reported a sexual intercourse history, and 7.6% noted a previous STI. Only 62.2% underwent free STI testing. Current smoking rates were 19.3% higher in AFABs. Hospital visit hesitation was reported by 59.6%, and 83.3% experienced daily mental struggles. Awareness of post-exposure prophylaxis and pre-exposure prophylaxis was low. Our findings highlight the urgent need for improved primary care and sexual health services for transgender people in Japan, emphasizing the necessity to increase sexual health care facilities, reduce primary care access barriers, and improve knowledge among health care providers.

Limited information exists about the types of immune cells present in Kaposi sarcoma (KS) lesions, especially in KS in the gastrointestinal tract. Using previously reported RNA-sequencing results from Kaposi sarcoma lesions in skin and gastrointestinal tract with normal matched tissues from the same patients at the same time, we investigated changes in lymphocytes in these tissues. We employed a computational method that determines changes in cell type distributions using KS lesion transcriptome data compared to a reference set of RNA expression patterns of purified immune cells. Since secreted cytokines and chemokines from KSHV-infected cells may influence the microenvironment of Kaposi sarcoma lesions, we performed cytokine profiling of conditioned media from KSHV-infected primary human dermal lymphatic endothelial cells. We also measured how this conditioned media altered the differentiation of macrophages in cell culture assays. These results suggested that factors in conditioned media from KSHV-infected endothelial cells promoted differentiation of a promonocytic cell line to proinflammatory macrophages.

In this editorial, we highlight the potential use of inhibitors of hypoxia-inducible factors (HIFs) for the use in Kaposi's sarcoma associated herpesvirus (KSHV) (also known as human herpesvirus-8) related malignancies. The past 20 years has accumulated detailed knowledge of the role of these factors in ensuring the maintenance of the KSHV in infected cells, in aiding the growth of the virus infected cells and aiding in the spread of virus from infected cells by inducing lytic reactivation. Today, a wide range of inhibitors for HIFs are currently being clinically evaluated for use in treating a variety of cancers. We discuss the current state of this research area as it relates to KSHV malignancies and describe pre-clinical and clinical evidence of drugs that target HIF to back up the idea that these inhibitors could be a novel way to treat KSHV related diseases.

Non-acquired immunodeficiency syndrome-defining malignancies (NADMs) are the crucial cause of mortality in people living with haemophilia and human immunodeficiency virus (PLWHH). We aimed to analyse the types and characters of NADMs in PLWHH after approval of direct-acting antivirals (DAA), considering that most PLWHH are infected with hepatitis C virus (HCV). We conducted a nationwide questionnaire mail survey across 395 HIV core facilities in Japan between May 2022 and February 2023. Eight-year data from 64 respondent hospitals (n = 328 PLWHH; 2015-2022) were collected; 35 NADM cases were identified and analysed. Standardised cancer incidence ratios (SCIRs) were calculated. The median age of PLWHH with NADMs was 51 years (interquartile range: 47-62 years); the SCIR was 2.08 (95% confidence interval [CI]: 1.48-2.90) for all malignancies (including carcinoma in situ). Liver cancer accounted for most NADMs (43% [15/35]). The SCIRs of liver cancer (23.09 [95% CI: 13.92- 38.30]) and papillary thyroid cancer (9.38 [2.35-37.50]) significantly increased after adjusting for general Japanese male sex and age. Among PLWHH with liver cancers, 73% (11/15) achieved HCV-sustained virological response. Notably, for patients aged ≤ 50 years, 47% (7/15) were affected by liver cancers, and 27% (4/15) succumbed to NADMs. This study presents the largest survey of NADMs in PLWHH after DAA approval. Our findings emphasised the elevated risk of malignancies in PLWHH, underscoring the need for early cancer screening and preventive measures, particularly against liver cancers, even in younger PLWHH.

The HIV/AIDS epidemic has changed significantly over the past 40 years. Changes in AIDS intervention strategies over time and across regions may have influenced epidemiological characteristics and intervention strategies. The aim of the current study was to analyze the changes in multi-year epidemiological characteristics of newly reported HIV/AIDS cases in an urban area (the Fengxian District of Shanghai) from 2001 to 2019 based on the national AIDS comprehensive data information system and Shanghai Statistical Yearbook. In total, the average annual incidence of HIV/AIDS was 1.92 per 100,000 persons. The annual incidence fluctuated and tended to increase from 2001 to 2019 (χ² = 128.38, p < 0.001). More male patients were reported compared to female patients, accounting for 82.9%. The proportion of patients over 65 years of age increased from 5% in 2009 to 12% in 2019. The majority of cases involved sexual contact (97.7%), early diagnosis (58.8%), full virologic suppression (72.9%), and early antiretroviral therapy (ART) (44.3%). Migrant patients have significantly increased over the years. There were significant differences between local and migrant patients in terms of the age at diagnosis, transmission route, and baseline CD4 count. The disparity in high-risk temporal clusters was also explored to indicate the delay of an epidemic between local patients and migrant patients. HIV remains at a low endemic level. AIDS prevention and control measures have been highly effective, and especially in virologic suppression of ART and early diagnosis. More efforts should be made to enhance early diagnosis and treatment among key vulnerable groups, including the elderly in the local population and young male migrants, and the scale of HIV/AIDS testing should be expanded to the general population to control HIV transmission.

Many circulating recombinant forms (CRFs) of HIV-1 have been reported, resulting in complex molecular epidemiology of HIV-1 infection. In this study, we newly identified CRF139_02B in Japan from 4 cases of anti-retroviral therapy naïve people living with HIV. Near full-length genome sequences of CRF139_02B were determined using Illumina MiSeq. Basic Local Alignment Search Tool (BLAST) revealed that there were several sequences having the same breakpoints as CRF139_02B in the UK and Nepal, though its full-length genome sequences were not available. Maximum clade credibility tree analysis using the region of protease and reverse transcriptase of HIV- 1 estimated that the time to the most recent common ancestor of CRF139_02B variants found in Japan was 2017.6 (95% highest posterior density interval: 2015.9-2019.3), and that among the UK, Nepal, and Japan was 2010.4 (2007.8- 2012.5). These results suggested that CRF139_02B circulated in Japan recently and domestically. Furthermore, the origin of CRF139_02B could be in the UK. Because there is a possibility that further international circulation of CRF139_02B may be observed in the near future, continuous monitoring of HIV-1 molecular epidemiology will be needed.

The study compared the level of perimenopausal syndrome (PS) among women age 40 or older living with HIV/AIDS (WLWH) and their HIV-negative counterparts in rural areas of Anhui, China and it analyzed the association between HIV infection and PS. From March 2018 to February 2019, WLWH ≥ the age of 40 and their aged-matched HIV-negative female neighbors in 8 townships in the cities of Fuyang and Bozhou in Anhui Province, China were selected by cluster random sampling to respond to a questionnaire survey. Multivariable logistic regression analysis was performed. Responses from a total of 464 participants were analyzed, including 220 HIV-positive women and 244 HIV-negative female neighbors. The average score for PS was 18.02 and the prevalence of PS was 85.0% in the HIV-positive group, both of which were higher than those in the control group (p < 0.05). The most common PS symptoms among WLWH were irritability (83.2%), followed by fatigue (79.5%) and arthralgia myalgia (68.2%). The risk of developing moderate to severe PS in HIV-uninfected women was 0.605 times that in WLWH. Other significant risk factors included being older, a history of chronic diseases, poor sleep quality, and poor appetite. In the future, more attention should be paid to the prevention of PS in WLWH while actively providing antiretroviral therapy and follow-up.