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Chlamydia trachomatis infection is the most common sexually transmitted infection (STI) worldwide. Because most infections are asymptomatic, sexual transmission generally occurs without notification. This aspect of transmission creates a risk [...]

During the 2022 global mpox outbreak, asymptomatic monkeypox virus (MPXV) infections or unrecognized mpox cases were reported among men who have sex with men (MSM) (1-4). Asymptomatic cases were diagnosed [...]

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]

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]

While global efforts have been made to prevent transmission of HIV, the epidemic persists. Men who have sex with men (MSM) are at high risk of infection. Despite evidence of its cost-effectiveness in other jurisdictions, pre-exposure prophylaxis (PrEP) for MSM is neither approved nor reimbursed in Japan. The cost-effectiveness analysis compared the use of once daily PrEP versus no PrEP among MSM over a 30-year time horizon from a national healthcare perspective. Epidemiological estimates for each of the 47 prefectures informed the model. Costs included HIV/AIDS treatment, HIV and testing for sexually transmitted infections, monitoring tests and consults, and hospitalization costs. Analyses included health and cost outcomes, as well as the incremental cost-effectiveness ratio (ICER) reported as the cost per quality-adjusted life year (QALY) for all of Japan and each prefecture. Sensitivity analyses were performed. The estimated proportion of HIV infections prevented with the use of PrEP ranged from 48% to 69% across Japan, over the time horizon. Cost savings due to lower monitoring costs and general medical costs were observed. Assuming 100% coverage, for Japan overall, daily use of PrEP costs less and was more effective; daily use of PrEP was cost-effective at a willingness to pay threshold of ¥5,000,000 per QALY in 32 of the 47 prefectures. Sensitivity analyses found that the ICER was most sensitive to the cost of PrEP. Compared to no PrEP use, once daily PrEP is a cost-effective strategy in Japanese MSM, reducing the clinical and economic burden associated with HIV. HIV remains an epidemic, and men who have sex with men (MSM) are at higher risk of infection. Pre-exposure prophylaxis (PrEP) is a preventive treatment that can reduce someone's risk of getting infected with HIV and has been shown to provide good value for money. PrEP, however, is neither approved nor reimbursed in Japan. In order to determine the value for money in Japan, an economic model was developed to estimate the number of HIV infections and AIDS cases that could be avoided, along with whether daily use of PrEP among MSM in Japan is cost effective. Findings showed that with use of daily PrEP, the proportion of HIV infections and AIDS cases prevented was 63% and 59%, respectively, across Japan. Over a 30-year time horizon, daily use of PrEP would cost the health system less and be more effective than no use of PrEP. Daily PrEP should therefore be considered for reimbursement in MSM in Japan, given its value for money. [ABSTRACT FROM AUTHOR]

Prolonged fever is a common symptom of COVID-19 infection. However, other febrile diseases continue during the pandemic. Herein, we report a COVID-19-infected patient with prolonged fever despite the lack of oxygen requirement, who was finally diagnosed with tuberculotic lymphadenitis and HIV-1 infection. All symptoms improved rapidly after the initiation of antituberculosis medications. Tuberculosis is an important differential diagnosis for patients with prolonged fever during the COVID-19 pandemic. It is possible that COVID-19 infection could serve to unmask latent infections via a cytokine storm. [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]

Objectives: To assess whether pooled sample testing with nucleic acid amplification tests was a potential alternative to three single-site sample testing to screen for Chlamydia trachomatis and Neisseria gonorrhoeae infections in asymptomatic men who have sex with men.Methods: We prospectively compared pooled sample testing with single-site sample testing in asymptomatic MSM. Self-obtained paired rectal samples, one gargle sample and one first-void urine sample were collected from participants to generate two sets of samples: one for pooled sample testing and the other for single-site testing. We used modified pooled sampling, which is defined as the use of gargle samples, instead of swabs, for the pooled sample to test for pharyngeal infection.Results: This study included 513 MSM. The positive rates of C. trachomatis and N. gonorrhoeae were 20.3% and 11.7%, respectively, for single-site sample testing. Compared with the sensitivity of single-site testing as the gold standard, the sensitivities of pooled sample testing for C. trachomatis and N. gonorrhoeae were 94.2% (95% CI 88.0% to 97.3%) and 98.3% (95% CI 90.9% to 99.9%), respectively. The concordance rate and kappa coefficient were 98.3% (95% CI 96.7% to 99.2%) and 0.945 (95% CI 0.859 to 1.000), respectively, for C. trachomatis and 98.8% (95% CI 90.1% to 100%) and 0.943 (95% CI 0.857 to 1.000), respectively, for N. gonorrhoeae.Conclusions: The modified pooled sampling had a comparably high consistency with single-site sample testing. The results strongly suggest that the gargle sample is suitable as a part of pooled sample for STI screening of C. trachomatis and N. gonorrhoeae. [ABSTRACT FROM AUTHOR]

Measurements performed using the self‐coupling effect of a semiconductor laser utilize an external resonator by exploiting the reflected light from the surface of an object. The improvement of the measurement accuracy due to the use of self‐coupled signals acquired from terminal voltages has not been thoroughly investigated. The current that flows through a semiconductor laser is adjusted so that its wavelength changes at a specific rate when it is modulated using an arbitrary waveform. As such, the spread of the self‐coupled signal is suppressed, and precision is improved. In addition, the accuracy is improved by considering the influence of lenses on the optical path. [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]

Introduction: Almost 30 years ago, about 30% of Japanese hemophiliacs became infected with HIV-1 and hepatitis C virus (HCV) after receiving contaminated blood products. While several studies have reported the high efficacy and safety of direct acting antivirals (DAA) in HIV-1 co-infected patients, such data are limited in hemophiliacs. Methods: We conducted a single-center, open-label study involving 27 Japanese patients (median age; 45 years) with inherited bleeding disorders who were co-infected with HCV/HIV-1. Patients with HCV genotype 1 (GT1) and GT4 received ledipasvir (90 mg) plus sofosbuvir (400 mg), those with HCV GT2 received sofosbuvir plus weight-based ribavirin, and those with HCV GT3 received daclatasvir (60 mg) plus sofosbuvir. Treatment was continued for 12 weeks in all patients. The primary endpoints were rate of sustained virologic response at 12 weeks after end of therapy (SVR12) and occurrence of adverse events during DAA therapy. Results: Eighteen (67%) patients had had received interferon-based therapy, and 11 (41%) had compensated cirrhosis. HCV genotypes were GT1a 4 (15%), GT1b 16 (59%), GT1 undetermined 2 (7%), GT2a 1 (4%), GT3a 3 (11%) and GT4a 1 (4%). All patients were on combination antiretroviral therapy (cART) and had undetectable HIV-1 viral load (<20 copies/μL) at baseline. All patients achieved SVR12. Serious adverse events were observed in 3 patients: arteritis of the leg, which resolved after completion of DAA therapy, asymptomatic QT prolongation and gastrointestinal hemorrhage. cART failure was noted in one patient due to emergence of raltegravir resistance during ledipasvir/sofosbuvir treatment. Although α-fetoprotein, Mac-2 binding protein glycosylation isomer (M2BPGi), and Fibro Scan (FS) scores decreased in most patients during DAA therapy, M2BPGi (>2.0 cutoff index) and FS scores (>15.0 kPa) were still high in 6 patients at week 36. Conclusions: DAA therapy is effective in all patients. However, adverse events and efficacy of cART should be monitored closely. [ABSTRACT FROM AUTHOR]

Background: The epidemiology of incident syphilis infection among HIV-1-infected men who have sex with men (MSM) largely remains unknown. Methods: The incidence and risk factors for incident syphilis (positive TPHA and RPR> = 1:8) among HIV-1-infected MSM who visited a large HIV clinic in Tokyo for the first time between 2008 and 2013 were determined, using clinical data and stored blood samples taken every three months for screening and determination of the date of incident syphilis. Poisson regression compared the incidence of syphilis at different observation periods. Results: Of 885 HIV-1-infected MSM with baseline data, 34% either presented with active syphilis at baseline (21%) or became infected with syphilis during follow-up (13%). After excluding 214 patients (MSM with syphilis at baseline (n = 190) and no follow-up syphilis test (n = 24)), of 671 men, 112 (17%) developed incident syphilis with an incidence of 43.7/1,000 person-years [95% CI, 36.5–52.3]. The incidence decreased slightly during observation period although the trend was not significant (2008–2009: 48.2/1,000 person-years, 2010–2011: 51.1/1,000 person-years, 2012–2013: 42.6/1,000 person-years, 2014 to 2015: 37.9/1,000 person-years, p = 0.315). Multivariable analysis identified young age (<33 years versus >40, HR 4.0, 95%CI 2.22–7.18, p<0.001), history of syphilis at baseline (HR 3.0, 95%CI 2.03–4.47, p<0.001), positive anti-amoeba antibody (HR 1.8, 95%CI 1.17–2.68, p = 0.006), and high baseline CD4 count (CD4 ≥350 /μL versus CD4 <200, HR 1.6, 95%CI 1.00–2.53, p = 0.050) as risk factors for incident syphilis. Incidence of syphilis was particularly high among young patients (age <33 years: 60.1/1,000 person-years). Interestingly, 37% of patients with incident syphilis were asymptomatic. Conclusions: Although incidence of syphilis did not increase during the observation period, it was high among HIV-1-infected MSM, especially among young HIV-1-infected MSM and those with history of syphilis, in Tokyo. Regular screening for syphilis needs to be strictly applied to this population. [ABSTRACT FROM AUTHOR]

Background: Loss to follow-up (LTFU) is viewed as a major challenge in improving retention in HIV treatment. In Vietnam, the reasons for disengagement from clinics and the effect of injection drug use (IDU) on LTFU with unknown outcome (true LTFU) are not well known. Methods: Patients receiving antiretroviral therapy (ART) from two HIV clinics in Hanoi were included in this observational study between 2007 and 2012, and followed up every 6 months until the end of 2013. The reasons for disengagement from the clinic, and ART status during imprisonment were investigated in patients with a history of IDU to identify true LTFU. The retention rate at 6–54 months and true LTFU rate were calculated. Cox proportional hazards regression models were performed to identify factors associated with true LTFU. Results: There were 1,431 patients, with a follow-up time of 4,371 person-years (median 2.49 years). At the end of the follow-up period, 71 (5.0%) patients died, 79 (5.5%) transferred to other clinics, 16 (1.1%) disengaged from the clinics, and the calculated true LTFU was 45 (3.1%), with 12-month ART retention rate of 95.3% for the entire study population. Imprisonment was the most frequent reason for disengagement from the clinics. True LTFU correlated significantly with low CD4 count and high plasma viral load, but not history of IDU. Conclusion: Imprisonment is a major cause of disengagement from HIV care among patients with a history of IDU. [ABSTRACT FROM AUTHOR]

HIV-infected patients are at high risk for bone mineral density (BMD) loss. The present study was designed to provide information on characteristics of BMD abnormalities in Japanese HIV-1-infected patients and risk factors involved in worsening of BMD. A total of 184 Japanese HIV-1-infected men were studied with a dual-energy X-ray absorptiometry scan (DXA) at the lumbar spine and femoral neck. Multivariate logistic regression models were used for comparison of the impact of risk factors on BMD loss. Osteopenia and osteoporosis were diagnosed in 46% and 10% of the patients at lumbar spine, and 54% and 12% at femoral neck, respectively. In logistic analysis, factors associated with low BMD at both lumbar spine and femoral neck were long-term treatment with a protease inhibitor (PI) [odds ratio (OR) 1.100 and 1.187 per 1 year increase of PI use; 95% confidence interval (CI) 1.003-1.207 and 1.043-1.351; p=0.042 and 0.009, respectively] and a low body mass index [OR: 0.938 and 0.852, CI 0.892-0.992 and 0.783-0.927; p=0.024 and <0.001, respectively]. Patients who discontinued PI had a significantly higher BMD than those who currently use PI at lumbar spine ( t score −0.8 vs. −1.3, p=0.04) but not at femoral neck (−1.3 vs. −1.5, p=0.38). In HIV-infected Japanese patients, the duration of treatment with PI correlated significantly with BMD loss. Discontinuation of PI is a promising option in the treatment of BMD loss since it allows recovery of BMD, especially in the lumbar spine. [ABSTRACT FROM AUTHOR]

Background: The efficacy of preemptive therapy against cytomegalovirus (CMV) infection remains unknown in treatment-naïve patients with advanced HIV-1 infection in the HAART era. Methods: The subjects of this single-center observation study were126 treatment-naïve HIV-1 infected patients with positive CMV viremia between January 1, 2000 and December 31, 2006. Inclusion criteria were age more than 17 years, CD4 count less than 100/μl, plasma CMV DNA positive, never having received antiretroviral therapy (ART) and no CMV end-organ disease (EOD) at first visit. The incidence of CMV-EOD was compared in patients with and without preemptive therapy against CMV-EOD. The effects of the CMV preemptive therapy were estimated in uni- and multivariate Cox hazards models. Results: CMV-EOD was diagnosed in 30 of the 96 patients of the non-preemptive therapy group (31%, 230.3 per 1000 person-years), compared with 3 of the 30 patients of the preemptive therapy group (10%, 60.9 per 1000 person-years). Univariate (HR = 0.286; 95%CI, 0.087–0.939; p = 0.039) and multivariate (adjusted HR = 0.170; 95%CI, 0.049–0.602; p = 0.005) analyses confirmed that CMV-EOD is significantly prevented by CMV preemptive therapy. Multivariate analysis showed that plasma CMV DNA level correlated significantly with CMV-EOD (per log10/ml, adjusted HR = 1.941; 95%CI, 1.266–2.975; p = 0.002). Among the 30 patients on preemptive therapy, 7 (23.3%) developed grade 3–4 leukopenia. The mortality rate was not significantly different between the two groups (p = 0.193, Log-rank test). Conclusions: The results indicate that preemptive therapy lowers the incidence of CMV-EOD by almost 25%. Preemptive therapy for treatment-naïve patients with CMV viremia is effective, although monitoring of potential treatment-related side effects is required. [ABSTRACT FROM AUTHOR]

Objective:The 2010 WHO antiretroviral therapy (ART) guidelines have resulted in increased tenofovir use. Little is known about tenofovir-induced chronic kidney disease (CKD) in HIV-infected Vietnamese with mean body weight of 55 kg. We evaluated the prevalence and risk factors of CKD in this country. Design:Cross-sectional study was performed. Methods:Clinical data on HIV-infected Vietnamese cohort were collected twice a year. To evaluate the prevalence of CKD, serum creatinine was measured in 771 patients in October 2011 and April 2012. CKD was defined as creatinine clearance less than 60 ml/min at both time points. Multivariate logistic regression was used to determine the factors associated with CKD Results:Tenofovir use increased in Vietnam from 11.9% in April 2011 to 40.3% in April 2012. CKD was diagnosed in 7.3%, of which 7% was considered moderate and 0.3% was severe. Multivariate analysis of October-2011 data identified age per year-increase (OR: 1.229, 95%CI, 1.170-1.291), body weight per 1 kg-decrement (1.286, 1.193-1.386), and tenofovir use (2.715, 1.028-7.168) as risk factors for CKD. Conclusions:Older age, low body weight and tenofovir use were independent risk factors for CKD in Vietnam. Further longitudinal study is required to evaluate the impact of TDF on renal function in Vietnam and other countries with small-body weight patients. [ABSTRACT FROM AUTHOR]

Background: Mycoplasma genitalium, which causes sexually transmitted diseases, is increasingly resistant to key antibiotics such as macrolides and quinolones, posing a challenge for treatment., Objectives: To assess the effectiveness of prolonged sitafloxacin and doxycycline combination therapy as a new alternative treatment strategy for highly drug-resistant M. genitalium strains., Methods: A prospective cohort study was conducted at the National Center for Global Health and Medicine, Tokyo, Japan, from 1 January 2020 to 31 October 2022. Patients with M. genitalium urogenital or rectal infections and those who did not receive the initial sitafloxacin monotherapy were included. Patients were administered sitafloxacin and doxycycline for 21 days as salvage therapy. M. genitalium isolates were tested for parC, gyrA and 23S rRNA resistance-associated mutations., Results: Twenty-seven patients received the combination therapy. All M. genitalium strains available for resistance analysis had parC (24/24) and macrolide resistance-associated (25/25) mutations, and 68% (17/25) had gyrA mutations. The overall cure rate was 77.8%. For strains with concurrent parC and gyrA mutations, the cure rate was 68.8% (P = 0.053) compared with that for monotherapy (37.5%)., Conclusions: Prolonged combination therapy is highly effective against M. genitalium strains with concurrent parC and gyrA mutations. Future research should focus on establishing the optimal treatment duration and monitoring the risk of resistance., (© The Author(s) 2024. Published by Oxford University Press on behalf of British Society for Antimicrobial Chemotherapy. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

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., Competing Interests: The authors have no conflicts of interest to disclose., (2024, National Center for Global Health and Medicine.)

Background: Pre-exposure prophylaxis (PrEP) against HIV infection is a new approach that involves the prophylactic use of the anti-HIV drug Truvada (tenofovir disoproxil fumarate [TDF] and emtricitabine [FTC]) by people not infected with HIV., Objective: The objective of this investigator-initiated clinical study of PrEP was to evaluate the incidence of HIV and sexually transmitted infection (STI), safety and efficacy of PrEP in PrEP users, and their compliance with PrEP medication. The social, medical, and economic benefits of PrEP in Japan was assessed., Methods: This single-center feasibility study of PrEP was conducted at the National Center for Global Health and Medicine, Tokyo, Japan, where a cohort of men who have sex with men without HIV was established in January 2017. This single-arm interventional study compared the efficacy and safety of PrEP in a single group of men who have sex with men who participated in PrEP cohort studies. For reference, the cohort study participants who did not participate in the PrEP study were included for comparison. Blood samples were collected for storage at baseline and clinic visits at 1, 3, and 6 months after starting PrEP and every 3 months thereafter. The participants were administered with 1 tablet of Truvada once daily as PrEP. They underwent blood and anal swab tests 1 and 3 months after starting PrEP and then HIV and STI infection assessments at 3-month intervals. Blood samples were centrifuged at the AIDS Clinical Center Laboratory. PrEP safety was evaluated by monitoring serum creatinine levels for symptoms of renal function disorders. The primary end point was the incidence of HIV in PrEP users (100 person-years). The secondary end points were the incidence of STI in PrEP users (100 person-years), incidence of adverse events caused by Truvada, frequency of high-risk sexual activity, and adherence to periodic visits and medication., Results: The study protocol was reviewed and approved by the certified review board of the National Center for Global Health and Medicine (NCGM-C-003129-03) on April 20, 2020. Changes to the study plan were submitted for review by the certified review board and approved before implementation. Recruitment was completed on March 28, 2019, and the study was completed (last adult participant and last time point) on March 31, 2021. The data were analyzed, and the main results of the study have been published in a peer-reviewed journal., Conclusions: The findings indicated that PrEP is a highly effective and feasible strategy against HIV infection in terms of prophylactic response, retention, and compliance., Trial Registration: UMIN Clinical Trials Registry UMIN000031040; https://tinyurl.com/3msdkeb8 and Japan Registry of Clinical Trials jRCTs031180134; https://tinyurl.com/2p88mhyr., International Registered Report Identifier (irrid): RR1-10.2196/50919., (©Junko Terada-Hirashima, Daisuke Mizushima, Misao Takano, Daisuke Tokita, Shinichi Oka. Originally published in JMIR Research Protocols (https://www.researchprotocols.org), 15.11.2023.)

Background: Mycoplasma genitalium is an emerging sexually transmitted pathogen associated with increasing antibiotic resistance. The current treatment guidelines recommend moxifloxacin-sequential therapy for macrolide-resistant Mgenitalium or strains with unknown resistance profiles. However, it is unclear whether sitafloxacin, a 4th-generation fluoroquinolone antibiotic, is effective against resistant strains., Objective: This study aims to assess and compare the efficacy and safety of sitafloxacin- and moxifloxacin-based treatment regimens for managing Mgenitalium infections., Methods: We will conduct this randomized controlled trial at multiple centers in Japan. Eligible participants include adults aged 18 years or older with a confirmed Mgenitalium infection, as determined through the nucleic acid amplification test. Patients will be randomly assigned using a stratified approach based on the treatment facility and infection site. The interventions comprise oral sitafloxacin (200 mg) daily for 7 days (with optional pretreatment of oral doxycycline, 200 mg, daily for up to 7 days), with a control group receiving oral doxycycline (200 mg) daily for 7 days followed by moxifloxacin (400 mg) daily for another 7 days. The primary outcome is the treatment success rate with a superiority margin of 10%, as confirmed through the nucleic acid amplification test. Secondary outcomes encompass changes in the bacterial load at the urogenital or rectal sites and the emergence of posttreatment-resistant mutant strains., Results: Enrollment commenced in June 2023 and will conclude in December 2024, with findings anticipated by 2025. The expected success rates fall within the range of 80% for sitafloxacin and 42% for moxifloxacin against Mgenitalium carrying the G248T (S83I) mutation, based on previous studies. Accordingly, with a 5% significance level (2-sided) and 80% statistical power, we aim to recruit 50 participants per group, factoring in a 10% expected dropout rate., Conclusions: This study will provide valuable insights into the efficacy and safety of sitafloxacin- versus moxifloxacin-based sequential therapy in treating Mgenitalium infections. These findings have the potential to influence clinical guidelines, favoring more effective therapeutic choices. The multicenter approach enhances the robustness of this study. However, a limitation is the potential insufficiency of statistical power to detect posttreatment-resistant mutant strains in each group, rendering posttreatment-resistance mutations a notable concern. In the future, we may need to increase the sample size to enhance power., Trial Registration: Japan Registry of Clinical Trials (jRCTs031230111); https://jrct.niph.go.jp/en-latest-detail/jRCTs031230111., International Registered Report Identifier (irrid): DERR1-10.2196/52565., (©Naokatsu Ando, Daisuke Mizushima, Yosuke Shimizu, Yukari Uemura, Misao Takano, Morika Mitobe, Kai Kobayashi, Hiroaki Kubota, Hirofumi Miyake, Jun Suzuki, Kenji Sadamasu, Takato Nakamoto, Takahiro Aoki, Koji Watanabe, Shinichi Oka, Hiroyuki Gatanaga. Originally published in JMIR Research Protocols (https://www.researchprotocols.org), 14.11.2023.)

Studies have shown that people living with HIV (PLWH) have a higher risk of having non-communicable diseases (NCDs) than do people without HIV. In Vietnam, HIV remains a major public health concern, and with recent rapid economic growth, NCDs such as diabetes mellitus (DM) have become a significant disease burden. This cross-sectional study was conducted to examine the prevalence of DM and the factors associated with DM among PLWH on antiretroviral therapy (ART). In total, 1,212 PLWH were included in the study. The age-standardized prevalence of DM and pre-diabetes were 9.29% and 10.32%, respectively. In the multivariate logistic regression analysis, male sex, age above 50 years, and body mass index ≥ 25 kg/m 2 were associated with DM, and borderline p-value was found for associations with current smoking and years on ART. The results suggest higher DM prevalence among PLWH and that longer time on ART could be an important risk factor for DM among PLWH. These findings also suggest that interventions such as weight control and smoking cessation support could be provided at outpatient clinics. Integration of HIV/AIDS and NCDs services is essential to address health needs comprehensively and enhance health-related quality of life for PLWH., Competing Interests: Shinichi Oka has received research grants from ViiV Healthcare and Gilead Sciences, as well as honoraria from MSD K.K., ViiV Healthcare, and Gilead Sciences. These research grants are not related to this study. The remaining authors declare no conflicts of interest., (2023, National Center for Global Health and Medicine.)

There is little evidence regarding the association between hepatitis B virus (HBV) chronicity and HLA-DP among the HIV-infected Vietnamese population. To study this, we conducted a cross-sectional analysis and a prospective study involving an HIV-infected Vietnamese cohort. The association between HBV chronicity and HLA-DP single nucleotide polymorphisms (SNPs) of rs3077 and rs9277535 among Vietnamese patients with previous HBV exposure was first evaluated. In addition, treatment-naive patients with chronic HBV infection were followed between 2012 and 2017 for HBV clearance after the initiation of antiretroviral therapy (ART). A total of 820 subjects with previous HBV exposure were included in the cross-sectional study. Among them, 147 (17.9 %) had chronic HBV infection, and 673 (82.1 %) achieved HBV clearance. The proportions of minor allele homozygotes of rs3077 and rs9277535 were 10.9 % and 15.2 % ( p = 0.481) and 4.1 % and 11.7 % ( p = 0.003), respectively. Multivariate analysis showed that rs9277535 minor homozygote was a significant protective factor against chronic HBV infection (odds ratio [OR], 0.271; 95 % confidence interval [CI]; 0.114-0.642, p = 0.001). Further, none of the 43 patients in the prospective study, who received ART possessed the rs9277535 minor homozygote. The average follow-up period was 4.8 years, and 10 subjects (23.3 %, 4.9 %/person-years) achieved HBV clearance. Univariate analysis revealed that the SNPs were not significantly associated with HBV clearance. In conclusion, our study confirmed that the rs9277535 minor allele homozygote was significantly associated with HBV clearance among HIV-infected Vietnamese patients., Competing Interests: S.O. has received research grants from ViiV Healthcare and Gilead Sciences, and honoraria for lectures from MSD K.K., ViiV Healthcare, and Gilead Sciences. H.G. received honoraria from MSD K.K., Abbott Japan, Co., Janssen Pharmaceutical K.K., Torii Pharmaceutical, Co., Roche Diagnostics K.K., and ViiV Healthcare, Co. The sponsors had no role in study design, collection, analysis and interpretation of data, article writing and publication decisions. The remaining authors have no conflicts of interest to disclose., (2022, National Center for Global Health and Medicine.)