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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]

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]

Objective: To examine the prevalence of illicit drug use among men who have sex with men (MSM) with HIV-1 infection in Japan, where the life-time prevalence of illicit drug use in the general population is only 2.9%. Design: A single-center cross-sectional study at a large HIV clinic in Tokyo, which treats approximately 15% of HIV-1 infected patients in Japan. Methods: The prevalence of illicit drug use and the assciation of characteristics and social demographics of the patients with illicit drug use were examined. Patients who visited the clinic for the first time from 2005 to 2010 were enrolled. Relevant variables were collected using a structured interview and from the medical records. Multivariate logistic regression analyses were applied to estimate the odds of association of MSM over non-MSM HIV-infected patients with illicit drug use. Results: 1,196 patients were enrolled. They were mostly Japanese men of relatively young age. Illicit drug use (including injection drugs) was reported by 35% of the patients (by 40% of MSM), and 4% were IDU while 5% were on methamphetamine. 2% of the population was arrested due to illicit drugs. MSM was significantly associated with illicit drug use (adjusted OR = 4.60; 95% CI, 2.88–7.36; p<0.01). Subgroup analysis of the patients stratified by three age groups (≤30, 31 to 40, and >40) showed that the odds of association of MSM with illicit drug use was the strongest in the youngest age group (≤30 years: adjusted OR = 7.56; 95% CI, 2.86–20.0; p<0.01), followed by the oldest (>40 years: adjusted OR = 6.15; 95% CI, 2.40–15.8; p<0.01), and the weakest in the group aged 31 to 40 (adjusted OR = 3.39; 95% CI, 1.73–6.63; p<0.01). Conclusions: The prevalence of illicit drug use is high among MSM patients with HIV-1 infection in Japan. Effective intervention for illicit drug use in this population is warranted. [ABSTRACT FROM AUTHOR]

Kidney tubulopathy is a well-known adverse event of antiretroviral agent tenofovir. A cross-sectional study was conducted to compare the diagnostic accuracy of five tubular markers, with a collection of abnormalities in these markers as the reference standard. The study subjects were patients with HIV-1 infection on ritonavir-boosted darunavir plus tenofovir/emtricitabine with suppressed viral load. Kidney tubular dysfunction (KTD) was predefined as the presence of at least three abnormalities in the following five parameters: β2-microglobulinuria (β2M), α1-microglobulinuria (α1M), high urinary N-acetyl-β- d-glucosaminidase (NAG), fractional excretion of phosphate (FE), and fractional excretion of uric acid (FE). Receiver operating characteristic curves and areas under the curves (AUC) were estimated, and the differences between the largest AUC and each of the other AUCs were tested using a nonparametric method. The cutoff value of each tubular marker was determined using raw data of 100 % sensitivity with maximal specificity. KTD was diagnosed in 19 of the 190 (10 %) patients. The AUCs (95 % CIs) of each tubular marker were β2M, 0.970 (0.947-0.992); α1M, 0.968 (0.944-0.992); NAG, 0.901 (0.828-0.974); FE, 0.757 (0.607-0.907), and FE, 0.762 (0.653-0.872). The AUCs of β2M and α1M were not significantly different, whereas those of the other three markers were smaller. The optimal cutoff values with 100 % sensitivity were 1,123 μg/gCr (β2M, specificity 89 %), 15.4 mg/gCr (α1M, specificity 87 %), 3.58 U/gCr (NAG, specificity 46 %), 1.02 % (FE, specificity 0 %), and 3.92 % (FE, specificity 12 %). Urinary β2M and α1M are potentially suitable screening tools for tenofovir-induced KTD. Monitoring either urinary β2M or α1M should be useful in early detection of tenofovir nephrotoxicity. [ABSTRACT FROM AUTHOR]

The association between tenofovir-induced kidney tubulopathy and polymorphisms in genes encoding transporters in Japanese patients was elucidated. Patients with genotypes −24 CC and 1249 AA of ABCC2 were almost 40 times more likely to develop tubulopathy than those without these genotypes.Background. Tenofovir is a widely used antiretroviral drug although it can cause kidney tubular dysfunction (KTD). The aim of this study was to determine the association between polymorphisms in genes encoding drug transporters and KTD in Japanese patients treated with tenofovir.Methods. The association between tenofovir-induced KTD and 14 single nucleotide polymorphisms (SNPs) in the ABCC2, ABCC4, ABCC10, SCL22A6, and ABCB1 genes was investigated in 190 Japanese patients. KTD was diagnosed by the presence of at least 3 abnormalities in the following parameters: fractional tubular resorption of phosphate, fractional excretion of uric acid, urinary β2-microglobulin, urinary α1-microglobulin, and urinary N-acetyl-β-D-glucosaminidase. Genotyping was performed by allelic discrimination using TaqMan 5′-nuclease assays with standard protocols. Associations between genotypes and KTD were tested by univariate and multivariate logistic regression analyses.Results. KTD was diagnosed in 19 of the 190 (10%) patients. Univariate and multivariate analyses showed a significant association between KTD and genotype CC at position −24 CC (adjusted odds ratio [OR], 20.08; 95% confidence interval [CI], 1.711–235.7; P = .017) and genotype AA at position 1249 (adjusted OR, 16.21; 95% CI, 1.630–161.1; P = .017) of ABCC2. Multivariate analysis showed higher adjusted OR for patients with both homozygotes (adjusted OR, 38.44; 95% CI, 2.051–720.4; P = .015). ABCC2 haplotype −24T and 1249G was a protective haplotype for KTD (OR, 0.098; 95% CI, .002–.603; P = .003Conclusions. This is the first study of our knowledge to identify the association between SNPs in ABCC2 and tenofovir-induced KTD in an Asian population. Close monitoring of renal function is warranted in tenofovir-treated patients with these SNPs. [ABSTRACT FROM AUTHOR]

Background:Loss to follow up (LTFU) is an important prognostic factor in patients with HIV-1 infection. The impact of illicit drug use on LTFU of patients with HIV-1 infection is unknown in Japan. Methods:A single center observational study was conducted to elucidate the impact of illicit drug use on LTFU at a large HIV clinic in Tokyo. LTFU was defined as those who discontinued their visits to the clinic for at least 12 months and were not known to be under the care of other facilities or have died within 12 months of their last visit. Patients who first visited the clinic between January 2005 and August 2010 were enrolled. Information on illicit drug use was collected in a structured interview and medical charts. Comparison of the effects of illicit drug use and no use on LTFU was conducted by uni- and multi-variate Cox hazards models as the primary exposure. Results:The study subjects were 1,208 patients, mostly Japanese men, of relatively young age, and infected through homosexual contact. A total of 111 patients (9.2%) were LTFU (incidence: 24.9 per 1,000 person-years). Among illicit drug users and non users, 55 (13.3%) and 56 (7.1%) patients, respectively, were LTFU, with incidence of 35.7 and 19.2 per 1,000 person-years, respectively. Uni- and multi-variate analyses showed that illicit drug use was a significant risk for LTFU (HR=1.860; 95% CI, 1.282-2.699; p=0.001) (adjusted HR=1.544; 95% CI, 1.028-2.318; p=0.036). Multivariate analysis also identified young age, high CD4 count, no antiretroviral therapy, and no health insurance as risk factors for LTFU. Conclusions:The incidence of LTFU among illicit drug users was almost twice higher than that among non users. Effective intervention for illicit drug use in this population is warranted to ensure proper treatment and prevent the spread of HIV. [ABSTRACT FROM AUTHOR]