Search

Pre-exposure prophylaxis (PrEP) with tenofovir/emtricitabine (TDF/FTC) has been recommended worldwide. We evaluated the safety and efficacy of daily PrEP with TDF/FTC in Tokyo. This single-center, single-arm study was performed with 124 men who have sex with men (MSM) between January 2017 and March 2021. MSM who entered into an MSM cohort from January 2017 through March 2018 and had a pre-PrEP observational period of 1 year were eligible and recruited to the study between April 2018 and March 2019 and followed for 2 years. The primary outcome was the incidence of HIV infection (per 100 person-years). Secondary outcomes were the incidence of sexually transmitted infections and adverse events, and the rate of retention and adherence to PrEP. There were 309 MSM registered in the cohort (mean age, 36.6 years); 124 fulfilled the criteria and were included in the study. The remaining patients were continuously followed. There was a significant decrease in incidental HIV infection among PrEP users (0 infections, 235.5 person-years) compared to non-PrEP users (11 infections [3.4%/year], 318.9 person-years; p = 0.01). The average adherence rate was consistently greater than 95%, and the retention rate at two years was approximately 80%. The present study showed a high prophylactic effect against HIV infection, retention, and adherence to PrEP. PrEP is feasible and highly recommended in Japan. UMIN Clinical Trials Registry (UMIN000031040, www.umin.ac.jp), Japan Registry of Clinical Trials (jRCTs031180134). [ABSTRACT FROM AUTHOR]

Objectives: To compare the effectiveness of doxycycline 100 mg twice daily for 7 days and azithromycin 1 g single dose for the treatment of rectal Chlamydia trachomatis infection among MSM in a real clinical setting.Methods: A prospective study was performed to compare the effectiveness of doxycycline and azithromycin for the treatment of rectal C. trachomatis among MSM in Tokyo, Japan. Subjects diagnosed with rectal C. trachomatis infection were treated and test-of-cure examination (TOC) was performed at least 3 weeks after the treatment. Treatment of rectal C. trachomatis infection was decided prospectively in a time-dependent manner; in the period between January 2017 and October 2018, azithromycin was administered to all subjects, whereas from October 2018 through March 2020, doxycycline was administered to all subjects. Effectiveness of these treatments was calculated by the number of rectal C. trachomatis-negative subjects at TOC divided by the number of subjects treated.Results: Two hundred and ninety-six MSM with rectal C. trachomatis infection were treated with azithromycin (80 patients) and doxycycline (216 patients) in a time-dependent manner. Of the 296 MSM, 274 (92.6%) were treated successfully [67 (83.7%, 95% CI = 79.6%-87.9%) in the azithromycin group versus 207 (95.8%, 95% CI = 94.5%-97.2%) in the doxycycline group, P < 0.001]. To evaluate factors associated with treatment failure, we performed logistic regression analysis. In univariate and multivariate analysis, only doxycycline treatment was inversely associated with treatment failure (OR = 0.29, 95% CI = 0.084-0.976, P = 0.046).Conclusions: The treatment with doxycycline 100 mg twice daily for 7 days was superior to that with azithromycin 1 g single dose for rectal C. trachomatis among MSM in a real-world setting. [ABSTRACT FROM AUTHOR]

Background: Rectal Chlamydia trachomatis (CT) and Neisseria gonorrhoeae (NG) infections have been neglected and epidemiological data are unavailable in Japan. Thus, we evaluated the prevalence and incidence of rectal CT/NG in a cohort of HIV-negative men who have sex with men (MSM), which was established at the National Center for Global Health and Medicine (NCGM), in Tokyo, Japan, in January 2017. Methods: HIV-negative MSM aged ≥16 years old were included. The prevalence of rectal CT/NG among HIV-negative MSM was compared with that among an existing HIV-positive MSM cohort at NCGM. The HIV-negative MSM cohort was examined for rectal and pharyngeal CT/NG every 3 months. Urethral CT/NG was evaluated at the physician's discretion. The incidences of CT/NG were evaluated in December 2018. Results: Of 502 MSM initially included in this study, 13 men were diagnosed with HIV infection at enrollment and were subsequently excluded from the analysis. We evaluated 561 HIV-positive MSM for rectal CT/NG. The mean ages of the two cohorts were 33.6 and 46.2 years old, respectively (p<0.001). The prevalences of rectal CT were 16.4% and 15.9% (p = 0.707) and the prevalences of rectal NG were 4.1% and 2.3% (p = 0.101), for the HIV-negative and HIV-positive MSM cohorts, respectively. Of 489 HIV-negative MSM, 328 were followed at least twice, with 261.1 person-years during the study period. The incidences of rectal CT/NG were 17.2 and 3.8/100 person-years and the incidences of pharyngeal CT/NG were 2.0 and 11.0/100 person-years for the two cohorts, respectively. Approximately 37.9% of incident cases were attributed to recurrent infection. Conclusions: The prevalence and incidence of rectal CT/NG were high among MSM in Tokyo, Japan, suggesting that urgent countermeasures for early diagnosis and treatment are necessary. [ABSTRACT FROM AUTHOR]

Background Mycoplasma genitalium has a tendency to develop macrolide and quinolone resistance. Objectives We investigated the microbiological cure rate of a 7 day course of sitafloxacin for the treatment of rectal and urogenital infections in MSM. Patients and methods This open-label, prospective cohort study was conducted at the National Center for Global Health and Medicine, Tokyo, Japan from January 2019 to August 2022. Patients with M. genitalium urogenital or rectal infections were included. The patients were treated with sitafloxacin 200 mg daily for 7 days. M. genitalium isolates were tested for parC , gyrA and 23S rRNA resistance-associated mutations. Results In total, 180 patients (median age, 35 years) were included in this study, of whom 77.0% (97/126) harboured parC mutations, including 71.4% (90/126) with G248T(S83I) in parC , and 22.5% (27/120) harboured gyrA mutations. The median time to test of cure was 21 days. The overall microbiological cure rate was 87.8%. The cure rate was 100% for microbes harbouring parC and gyrA WTs, 92.9% for microbes harbouring parC G248T(S83I) and gyrA WT, and 41.7% for microbes harbouring parC G248T(S83I) and gyrA with mutations. The cure rate did not differ significantly between urogenital and rectal infection (P  = 0.359). Conclusions Sitafloxacin monotherapy was highly effective against infection caused by M. genitalium , except strains with combined parC and gyrA mutations. Sitafloxacin monotherapy can be used as a first-line treatment for M. genitalium infections in settings with a high prevalence of parC mutations and a low prevalence of gyrA mutations. [ABSTRACT FROM AUTHOR]

Background: Japan has not succeeded in reducing the annual number of new HIV-infected patients, although the prevalence of HIV infection is low (0.02%). Methods: A single-center observational study was conducted at the largest HIV clinic in Tokyo, which treats 15% of the total patients in Japan, to determine the reasons for having diagnostic tests in newly infected individuals. HIV-infected patients who visited our clinic for the first time between 2011 and 2014 were analyzed. Results: The 598 study patients comprised one-third of the total reported number of new patients in Tokyo during the study period. 76% were Japanese MSM. The reasons for being tested which led to the diagnosis was voluntary testing in 32%, existing diseases in 53% (AIDS-defining diseases in 22%, sexually transmitted infections (STI) in 8%, diseases other than AIDS or STIs in 23%) and routine pre-surgery or on admission screening in 15%. 52% and 74% of the study patients and patients presented with AIDS, respectively, had never been tested. The median CD4 count in patients with history of previous testing (315/μL) was significantly higher than that of patients who had never been tested (203/μL, p<0.001). Conclusions: Only 32% of the newly HIV diagnosed patients were diagnosed because of voluntary testing, and 53% were diagnosed due to presence of other diseases. These results remain unchanged from our previous report 10 years earlier (2000–2004) on newly diagnosed patients at the same clinic. HIV testing has not been widely used by newly diagnosed patients in the Tokyo metropolitan area. [ABSTRACT FROM AUTHOR]

Background: Amebiasis, caused by Entamoeba histolytica, is spreading in developing countries and in many developed countries as a sexually transmitted infection. Here, we evaluated the efficacy of serological screening to identify asymptomatic E. histolytica infection as a potential epidemiological control measure to limit its spread. Methodology/Principal findings: This cross-sectional study was carried out between January and March 2021 in an HIV-negative men who have sex with men (MSM) cohort at the National Center for Global Health and Medicine. Serological screening was performed using a commercially available ELISA kit. For seropositive individuals, we performed stool polymerase chain reaction (PCR) to determine current E. histolytica infection. We performed E. histolytica serological screening of 312 participants. None had a history of E. histolytica infection prior to the study. The overall E. histolytica seropositivity was 6.7% (21/312), which was similar to that found by the rapid plasma reagin test (17/312). We identified current infection in 8 of 20 seropositive participants (40.0%) by stool PCR. Conclusions/Significance: Our serological screening approach constitutes a potentially practical epidemiological strategy. Active epidemiological surveys, in combination with an effective screening strategy for asymptomatically infected individuals, should be applied to help reduce sexually transmitted E. histolytica infections. Author summary: Amebiasis, caused by Entamoeba histolytica, is now spreading not only in developing countries, but also in many of developed countries. Unlike the situation in developing countries, transmission occurs directly from one infected person to another via sexual contact, called sexually transmitted E. histolytica infection. Furthermore, most cases of E. histolytica infection are asymptomatic, who can be a reservoir for sexual transmission in the community. Cost-effective epidemiological strategy is urgently needed. Hereby, we performed a serological test for 312 "asymptomatic" HIV-negative men who have sex with men to assess the effective screening method for E. histolytica infection. We identified 21 seropositive samples (6.7% of seropositivity, 21/312), in which relatively high seropositivity to E. histolytica was seen among the participants with positive serology for Treponema pallidum hemagglutination (TPHA) or hepatitis B core antibody (HBcAb). Finally, we identified current infection (asymptomatic E. histolytica infection) in 8 out of 20 stool sampling cases (40.0%) by polymerase chain reaction. Our serological screening assay provides a potentially practical epidemiological strategy. Active epidemiological survey, in combination with the effective screening strategy for asymptomatically infected individuals are considered for the future control of sexually transmitted E. histolytica infection. [ABSTRACT FROM AUTHOR]

Background Evidence on efficacy of high-dose ceftriaxone monotherapy for extragenital Neisseria gonorrhoeae (NG) infection is lacking. Methods A cohort of men who have sex with men (MSM) were tested for NG/ Chlamydia trachomatis (CT) every 3 months, in a single-center observational study in Tokyo, Japan. MSM aged > 19 years diagnosed with extragenital NG infection between 2017 and 2020 were included. A single dose of 1 g ceftriaxone monotherapy was provided, while dual therapy with a single oral dose of 1 g azithromycin or 100 mg doxycycline administered orally twice daily for 7 days were given, for those coinfected with CT, according to infected sites. Efficacy of these treatments was calculated by the number of NG-negative subjects at test-of-cure divided by the number of subjects treated. Fisher exact tests were used to compare the efficacy between the 2 groups. Results Of 320 cases diagnosed with extragenital NG, 208 were treated with monotherapy and 112 were treated with dual therapy. The efficacy against total, pharyngeal, and rectal infections was 98.1% (204/208, 95% confidence interval [CI]: 95.2–99.3%), 97.8% (135/138, 95% CI: 93.8–99.4%), and 98.6% (69/70, 95% CI: 92.3–99.9%), respectively, in the monotherapy group, whereas the corresponding efficacy in the dual therapy was 95.5% (107/112, 95% CI: 90.0–98.1%), 96.1% (49/51, 95% CI: 86.8–99.3%), and 95.1% (58/61, 95% CI: 86.5–98.7%), respectively. No significant difference in the corresponding efficacy was observed between the two groups (P  = .29, P  = .61, P  = .34, respectively). Conclusions High-dose ceftriaxone monotherapy is as effective as dual therapy for extragenital NG among MSM. [ABSTRACT FROM AUTHOR]

Anal high-risk human papillomavirus (hr-HPV) infection is widely considered a cause of anal cancer. However, epidemiological data are quite limited in Japan. This study investigated anal HPV infections and cytological abnormalities among MSM with or without HIV infection. Anal swabs were obtained, and cytological results were examined. Hybrid capture-based methodology was used for hr-HPV genotyping. The exclusion criterion was a history of vaccination against HPV. 644 subjects participated, and the overall prevalence of hr-HPV was 59.7% (95% CI 54.7–62.3), HIV-infected had higher prevalence than HIV-uninfected (68.9% vs 40.6%) p <.001. Among hr-HPV-infected participants, 82.8% (312/377) were infected with at least one of 9 valent vaccine-covered hr-HPV genotypes. From regression analysis, detection of abnormal cytology correlated positively with HIV infection (OR 2.17 [95% CI 1.51–3.13]), number of hr-HPV genotypes infected (OR 1.83 [1.59–2.10]), history of STI (OR 1.58 [1.14–2.22]) and No. of lifetime sexual partners (OR 1.56 [1.10–2.21]), albeit multivariate analysis identified the number of detected hr-HPV genotypes (adjusted OR 1.78 [1.54–2.06]) as the independent risk factor for abnormal cytology. High rates of anal hr-HPV infection, especially 9-valent HPV vaccine-preventable hr-HPV were detected among our MSM participants in Japan. HPV vaccination should also be encouraged for MSM in Japan. [ABSTRACT FROM AUTHOR]

Background: Men who have sex with men (MSM) are at high risk of HIV infection. However, there are only few data on HIV prevalence in MSM in Japan. The objective of this study was to explore the HIV prevalence in MSM at Shinjuku 2-chome, a well known gay quarter in Tokyo.Methods: MSM directly collected the dried blood spot (DBS) self-collection HIV test kit from a drop-in center in Shinjuku 2-chome between August 2015 and December 2016. The participants collected their own blood by finger-prick and anonymously posted the kit to the laboratory. The participants accessed the study website and checked the results of their tests using unique ID and password. DBS was soaked in phosphate buffered saline overnight and the eluted sample was examined by the fourth generation HIV Ag/Ab test of LUMIPULSE (FUJIREBIO INC.), and followed by HISCL (Sysmex Corp.) when the first assay was positive. The result was defined provisionally positive if both were positive.Results: A total of 1702 HIV test kits were distributed and 1403 DBS were returned (return rate: 82.4%). Since 20.2% of participants collected the test kit more than once, the estimated number of actual test kit users was 1120. Based on the results of the test kit, 34 cases were provisionally diagnosed with HIV. The estimated prevalence was 3.04% (95% confidence interval: 2.03-4.04). Of these 34, 24 (70.6%) were later confirmed to be HIV-positive in the hospital, while the remaining 10 were lost to follow-up. Among the participants, 34.5% received HIV test for the first time. Especially in those aged 20-29, 46.0% were first time HIV testers.Conclusions: The prevalence of HIV infection in the study population was 3.04%. The high collection suggested a demand for this type of testing in MSM. The test should be expanded further to difficult-to-reach or hidden populations.Trial Registration: This study was registered with the University Hospital Medical Information Network Clinical Trial Registry in August 20th, 2015 (Registry number: UMIN000018699 ). [ABSTRACT FROM AUTHOR]

Background Amoxicillin plus probenecid is an alternative to intramuscular benzathine penicillin G for treating syphilis in the United Kingdom. Low-dose amoxicillin is an alternative treatment option used in Japan. Methods We conducted an open-label, randomized, controlled, non-inferiority trial between 31 August 2018, and 3 February 2022, to compare 1500 mg low-dose amoxicillin monotherapy with the combination of 3000 mg amoxicillin and probenecid (non-inferiority margin 10%). Patients with human immunodeficiency virus (HIV) infection and syphilis were eligible. The primary outcome was the cumulative serological cure rate within 12 months post-treatment, measured using the manual rapid plasma reagin card test. Secondary outcomes included safety assessment. Results A total of 112 participants were randomized into 2 groups. Serological cure rates within 12 months were 90.6% and 94.4% with the low-dose amoxicillin and combination regimens, respectively. Serological cure rates for early syphilis within 12 months were 93.5% and 97.9% with the low-dose amoxicillin and combination regimens, respectively. Non-inferiority of low-dose amoxicillin compared with amoxicillin plus probenecid overall and for early syphilis was not confirmed. No significant side effects were detected. Conclusions This is the first randomized controlled trial to demonstrate a high efficacy of amoxicillin-based regimens for treating syphilis in patients with HIV infection, and the non-inferiority of low-dose amoxicillin compared with amoxicillin plus probenecid was not seen. Therefore, amoxicillin monotherapy could be a good alternative to intramuscular benzathine penicillin G with fewer side effects. However, further studies comparing with benzathine penicillin G in different populations and with larger sample sizes are needed. Trials Registration (UMIN000033986). [ABSTRACT FROM AUTHOR]

Objective: Our previous 2005–2009 molecular epidemiological study in Mongolia identified a hot spot of HIV-1 transmission in men who have sex with men (MSM). To control the infection, we collaborated with NGOs to promote safer sex and HIV testing since mid-2010. In this study, we carried out the second molecular epidemiological survey between 2010 and 2016 to determine the status of HIV-1 infection in Mongolia. Methods: The study included 143 new cases of HIV-1 infection. Viral RNA was extracted from stocked plasma samples and sequenced for the pol and the env regions using the Sanger method. Near-full length sequencing using MiSeq was performed in 3 patients who were suspected to be infected with recombinant HIV-1. Phylogenetic analysis was performed using the neighbor-joining method and Bayesian Markov chain Monte Carlo method. Results: MSM was the main transmission route in the previous and current studies. However, heterosexual route showed a significant increase in recent years. Phylogenetic analysis documented three taxa; Mongolian B, Korean B, and CRF51_01B, though the former two were also observed in the previous study. CRF51_01B, which originated from Singapore and Malaysia, was confirmed by near-full length sequencing. Although these strains were mainly detected in MSM, they were also found in increasing numbers of heterosexual males and females. Bayesian phylogenetic analysis estimated transmission of CRF51_01B into Mongolia around early 2000s. An extended Bayesian skyline plot showed a rapid increase in the effective population size of Mongolian B cluster around 2004 and that of CRF51_01B cluster around 2011. Conclusions: HIV-1 infection might expand to the general population in Mongolia. Our study documented a new cluster of HIV-1 transmission, enhancing our understanding of the epidemiological status of HIV-1 in Mongolia. [ABSTRACT FROM AUTHOR]

Men who have sex with men (MSM) have been disproportionally affected by the HIV epidemic in many countries, including Japan. Although pre-exposure prophylaxis (PrEP) is a strong prevention tool, it is not yet approved in Japan. A Markov model was developed to describe HIV infection and disease progression in an MSM cohort (N = 1000) in Japan receiving a PrEP program. The model was used to evaluate the cost-effectiveness of a PrEP program. HIV/AIDS treatment, screening, hospitalization due to AIDS, and PrEP were considered as costs and quality-adjusted life-years (QALYs) gained as utilities. Cost-effectiveness was assessed by comparing the incremental cost-effectiveness ratio (ICER) over a 30-year period against the willingness to pay (WTP) threshold. One-way sensitivity and probabilistic sensitivity analyses were performed. With 50% PrEP coverage, the PrEP program became dominant against the program without PrEP, using a threshold of 5.0 million JPY/QALY (45,455 USD). The probabilistic sensitivity analysis revealed that the PrEP program was dominant or at least cost-effective in most cases of 10,000 simulations. Therefore, preparing cheaper PrEP pills, which results in PrEP being dominant or ICER being lower than the WTP threshold, is important to make the program cost-effective. Introduction of PrEP to an MSM cohort in Japan would be cost-effective over a 30-year time horizon. [ABSTRACT FROM AUTHOR]

This single-institution cross-sectional study aimed to grasp the prevalence and features of neurocognitive dysfunction in HIV-infected hemophilia patients in Japan. We conducted neuropsychological tests and medical examinations in 56 HIV-infected hemophilia patients who received outpatient treatment at the AIDS Clinical Center, National Center for Global Health and Medicine. A total of 388 HIV-infected non-hemophilia patients who received outpatient treatment at the same institution were included as a control group. To investigate sites responsible for neurocognitive dysfunction in HIV-infected hemophilia patients using brain FDG-PET/CT scans, the accumulation of FDG in each brain region was compared. Approximately 50% of HIV-infected hemophilia patients had neurocognitive dysfunction. The prevalence of asymptomatic neurocognitive impairment was high (34%). Neurocognitive dysfunction was associated with educational level in HIV-infected hemophilia patients. In the symptomatic group, hemophilic arthropathy and history of cerebrovascular disorders were associated with neurocognitive dysfunction. Left temporal lobe function was reduced in the symptomatic group. [ABSTRACT FROM AUTHOR]

There is no detailed information on the association between age, time of disease, and HIV-associated neurocognitive disorders (HAND). In this prospective study involving 17 medical facilities across Japan, we recruited HIV-infected patients to complete a 14-test neuropsychological battery that assess eight neurocognitive domains. HAND were diagnosed by the Frascati criteria. Of 1399 recruited patients, 728 were enrolled. The prevalence of HAND was 25.3% [13.5% asymptomatic neurocognitive impairment, 10.6% mild neurocognitive disorder (MND), and 1.2% HIV-associated dementia (HAD)]. Tests that assess executive and visuospatial functions showed better diagnostic accuracy than other tests for HAND. Multivariate analysis identified age (≥ 50 years) and incomplete virological suppression as risk factors for MND and HAD and current ART as a protective factor. The prevalence of MND and HAD was low in the early stage of infection (6.3% in ≥ 2 to < 6 years), then increased in the later stage [17.3% in ≥ 11 years, p = 0.001 (vs. ≥ 2 to < 6 years)], independent of age or treatment. Older patients were more likely to show MND or HAD in the early stage of HIV infection (26.7 vs. 8.7% for < 2 years and 17.4 vs. 3.1% for ≥ 2 to < 6 years, p = 0.040 and 0.004, respectively) compared to younger ones. In conclusion, MND and HAD were more commonly found in later years since diagnosis of HIV infection and older patients are at risk of neurocognitive impairment at the early stage of HIV infection. Tests for executive and visuospatial functions seem more sensitive than other tests for diagnosing HAND. [ABSTRACT FROM AUTHOR]