Incidence of recurrent ischemic stroke and its associated factors in a tertiary care center in Thailand: a retrospective cohort study.

BACKGROUND: Ischemic stroke (IS) is one of the leading causes of death among non-communicable diseases in Thailand. Patients who have survived an IS are at an increased risk of developing recurrent IS, which can result in worse outcomes and post-stroke complications. OBJECTIVES: The study aimed to investigate the incidence of recurrent IS among patients with first-ever IS during a one-year follow-up period and to determine its associated risk factors. METHODS: Adult patients (aged ≥ 18 years) who were hospitalized at the Stroke Center, King Chulalongkorn Memorial Hospital (KCMH) in Bangkok, Thailand, due to first-ever IS between January and December 2019 and had at least one follow-up visit during the one-year follow-up period were included in this retrospective cohort study. IS diagnosis was confirmed by neurologists and imaging. The log-rank test was used to determine the event-free survival probabilities of recurrent IS in each risk factor. RESULTS: Of 418 patients hospitalized due to first-ever IS in 2019, 366 (87.6%) were included in the analysis. During a total of 327.2 person-years of follow-up, 25 (6.8%) patients developed recurrent IS, accounting for an incidence rate of 7.7 per 100 person-year (95% confidence interval [CI] 5.2-11.3). The median (interquartile range) time of recurrence was 35 (16-73) days. None of the 47 patients with atrial fibrillation developed recurrent IS. The highest incidence rate of recurrent IS occurred within 1 month after the first episode (34 per 100 person-years) compared to other follow-up periods. Patients with small vessel occlusion and large-artery atherosclerosis (LAA) constituted the majority of patients in the recurrent IS episode (48% and 40%, respectively), with LAA exhibiting a higher recurrence rate (13.5%). Additionally, smoking status was found to be associated with an increased risk of recurrence. CONCLUSION: The incidence rate of the recurrence was moderate in our tertiary care setting, with a decreasing trend over time after the first episode. The various subtypes of IS and smoking status can lead to differences in event-free survival probabilities.

Framingham risk score based vascular outcomes in acute versus chronic HIV cohorts after 6 years of ART.

INTRODUCTION: Immune dysregulation persists in people with HIV (PWH) on antiretroviral therapy (ART) and may lead to accelerated vascular ageing and cardiovascular disease (CVD). While delayed time to initiation of ART has been linked to worse cardiovascular outcomes, the effect of ART initiation during acute infection on these outcomes is not well understood. METHODS: Participants were enrolled from the SEARCH010/RV254 acute HIV (AHI) and HIV-NAT chronic HIV (CHI) cohorts in Thailand. Participants with 6-year follow-up and viral suppression (viral load < 50 copies/µL) at follow-up were included. Both unmatched cohorts and age and gender-matched cohorts were analysed. Demographics, HIV laboratories, and cardiovascular risk factors from enrolment and 6-year follow-up were obtained from electronic records. Framingham Risk Score (FRS), vascular age (VA), vascular age deviation (VAD), and 10-year atherosclerotic cardiovascular disease (ASCVD) risk were calculated from previously published equations. Vascular outcomes in AHI and CHI cohorts were compared, and univariable and multivariable linear regression analyses were used to investigate risk factors associated with worse vascular scores. RESULTS: In all, 373 AHI participants and 608 CHI participants were identified. AHI participants were of younger age, had a higher prevalence of syphilis and a lower prevalence of prior hepatitis B, tuberculosis, diabetes, and hypertension. Higher CD4 T-cell and lower CD8 T-cell counts were seen in the AHI cohort at enrolment and 6-year follow-up. In all participants, the AHI cohort had a lower median FRS (p < 0.001) and VA (p < 0.001), but higher VAD (p < 0.001). However, in matched cohorts, no differences were found in FRS-based outcomes. In all participants, higher VAD after 6 years of ART was associated with higher body mass index (p < 0.001) and higher CD4 count (p < 0.001), which persisted in multivariable analysis. When FRS components were analysed individually, CD4 count was associated only with male sex and cholesterol. CONCLUSIONS: We did not identify differences in FRS-based vascular outcomes at 6 years in matched cohorts of participants who started ART during AHI versus CHI. We identified a correlation between higher CD4 count and worse FRS-based vascular outcomes, which may be driven by underlying metabolic risk factors. Further study is needed to confirm these findings and evaluate underlying mechanisms.

Neurofilament light chain for classifying the aetiology of alteration of consciousness.

Neurofilament light chain has become a promising biomarker for neuroaxonal injury; however, its diagnostic utility is limited to chronic disorders or specific contexts. Alteration of consciousness is a common clinical problem with diverse aetiologies, many of which require timely diagnoses. We evaluated the value of neurofilament light chain alone, as well as creating diagnostic models, in distinguishing causes of alteration of consciousness. Patients presenting with alteration of consciousness were enrolled. Initial clinical data of each participant were evaluated by a neurologist to give a provisional diagnosis. Each participant subsequently received advanced investigations and follow-up to conclude the final diagnosis. All diagnoses were classified into a structural or non-structural cause of alteration of consciousness. Plasma and cerebrospinal fluid levels of neurofilament light chain were measured. Cerebrospinal fluid neurofilament light chain and other clinical parameters were used to develop logistic regression models. The performance of cerebrospinal fluid neurofilament light chain, the neurologist's provisional diagnosis, and the model to predict the final diagnosis were compared. For the results, among 71 participants enrolled, 67.6% and 32.4% of their final diagnoses were classified as structural and non-structural, respectively. Cerebrospinal fluid neurofilament light chain demonstrated an area under the curve of 0.75 (95% confidence interval 0.63-0.88) which was not significantly different from a neurologist's provisional diagnosis 0.85 (95% confidence interval 0.75-0.94) (P = 0.14). The multivariable regression model using cerebrospinal fluid neurofilament light chain and other basic clinical data achieved an area under the curve of 0.90 (95% confidence interval 0.83-0.98). In conclusion, neurofilament light chain classified causes of alteration of consciousness with moderate accuracy. Nevertheless, including other basic clinical data to construct a model improved the performance to a level that was comparable to clinical neurologists.

Impact of steatotic liver disease and non-alcoholic steatohepatitis on cognitive impairment in people living with HIV: A cross-sectional study.

INTRODUCTION: The link between fatty liver diseases and cognitive impairment among people living with HIV (PLWH) remains unclear. We investigated the association of steatotic liver disease (SLD), advanced liver fibrosis and non-alcoholic steatohepatitis (NASH) with significant activity and liver fibrosis with cognitive impairment in PLWH. METHODS: Cognitive performance was assessed for PLWH aged ≥50 years on stable antiretroviral therapy (ART) with the Thai-validated version of the Montreal Cognitive Assessment (MoCA), and a cut-off of <25/30 was used to define cognitive impairment. SLD and NASH with significant activity and liver fibrosis were defined as having a controlled attenuation parameter value ≥248 dB/m and a FibroScan-AST (FAST) score ≥0.67, respectively. Multivariable logistic regression was employed to investigate the association of cognitive impairment with SLD or NASH. RESULTS: Of the 319 PLWH (63.3% male and 98% had HIV-1 RNA ≤50 copies/mL) included, 74 (38%) had SLD. NASH with significant activity and liver fibrosis was present in 66 (20.1%) participants. Some 192 (60.2%) participants had cognitive impairment. In a multivariable analysis, NASH with significant activity and liver fibrosis was significantly associated with cognitive impairment (adjusted odds ratio [aOR] 2.01, 95% CI 1.02-3.98, p = 0.04), after adjusting for HIV-related parameters, age, sex, body mass index, employment status, education, income level, smoking, alcohol use, diabetes mellitus, hypertension and HIV-related parameters. The association of a lone diagnosis of SLD and cognitive impairment was not statistically significant. CONCLUSIONS: NASH with significant activity and liver fibrosis was associated with lower cognitive performance, even after controlling for demographics and HIV disease parameters. Additional research is needed to better understand the underlying mechanisms.

Pooled Pharyngeal, Rectal, and Urine Specimens for the Point-of-Care Detection of Chlamydia trachomatis and Neisseria gonorrhoeae by Lay Providers in Key Population-Led Health Services in Thailand.

Routine testing for Chlamydia trachomatis (CT) and Neisseria gonorrhoeae (NG) in people with heightened risk is lacking in Thailand. This study aimed to assess the performance of the Cepheid Xpert CT/NG assay, conducted by key population (KP) lay providers, for CT and NG detection on single-site and pooled specimens from the pharynx, rectum, and urine. Between August and October 2019, 188 men who have sex with men and 11 transgender women were enrolled. Participants collected urine specimens while trained KP lay providers obtained pharyngeal and rectal swabs. Compared to single-site testing with the Abbott RealTime CT/NG assay by medical technologists, the Xpert assay missed one pharyngeal NG infection out of 199 single-site specimens, giving a 93.3% sensitivity for pharyngeal NG and one missed pharyngeal NG infection out of fifty pooled specimens, giving an 88.9% sensitivity for pharyngeal NG. There was no discrepancy between the two assays for CT detection. The Cohen's Kappa coefficient of pooled specimen testing by the Xpert was 0.93 for NG and 1 for CT when compared to single-site testing by Abbott. Implementing pooled specimen testing by KP lay providers can be a cost-saving strategy to enhance the uptake of CT/NG services for populations facing increased risk.

Real-time quaking-induced conversion assay using a small-scale substrate production workflow for the diagnosis of Creutzfeldt-Jakob disease.

The lack of a dedicated surveillance program for prion disease, particularly in low- and middle-income countries (LMICs), has hindered the global effort to address this public health threat. Although cerebrospinal fluid (CSF) Real-time quaking-induced conversion (RT-QuIC) is considered the most reliable test for sporadic Creutzfeldt-Jakob disease (sCJD), its availability in LMICs is limited because of its cost and technical difficulty in generating the recombinant prion protein substrate (recPrP). This study aimed to evaluate the performance of RT-QuIC with recPrP produced in-house through a small-scale method-that is, the application of reusable prepacked chromatography columns and subsequent dialysis. Here, CSF specimens from patients suspected of having prion disease were consecutively collected and stored between October 2015 and January 2023. Electronic medical record data were reviewed to clinically classify participants as probable sCJD or non-sCJD. CSF RT-QuIC was performed using in-house recPrP. Its specificity and sensitivity for diagnosing probable sCJD were reported, along with details of other clinical data and investigations. We found that among 39 eligible participants, with a median (interquartile range) age of 64 (56-70) years and 16 (41%) female, 13 had probable sCJD and the remaining 26 unequivocally suffered from nonprion disorders. Magnetic resonance imaging and electroencephalogram were suggestive of sCJD in 100% (13/13) and 46.2% (6/13) of sCJD participants, respectively. RT-QuIC was positive in 12/13 sCJD participants (sensitivity 0.92, 95% confidence interval [CI] 0.67-0.99) and negative in all non-sCJD participants (specificity 1.00, 95% CI 0.87-1.00). CSF tau/p-tau ratio showed sensitivity and specificity of 0.62-1.0 and 0.85-1.0, respectively. In summary, RT-QuIC using recPrP generated through a small-scale workflow demonstrated great performance in detecting sCJD. Given its performance results along with its low cost, this technique could feasibly be implemented in LMICs and potentially be the first step toward establishing local prion disease surveillance programs.

Estradiol and Testosterone Concentrations Among Thai Transgender Women in a Transgender-Led, Integrated Gender-Affirming Care and Sexual Health Clinic: A Real-World Analysis.

Purpose: Feminizing hormone therapy (FHT) is used by many transgender women as a pharmacological method to mitigate gender dysphoria. However, information on hormone concentrations among those who use FHT is lacking. We aimed to determine the proportion of Thai transgender women who were using FHT who had hormone concentrations within target ranges in a real-world clinic setting. Methods: Transgender women who attended Tangerine Clinic in Bangkok, Thailand, reported current use of FHT at clinic entry, and tested for both blood estradiol (E2) and total testosterone (TT) concentrations were included in the analysis. Hormone target concentrations were defined as 100-200 pg/mL for E2 and <50 ng/dL for TT. Results: Of 1534 transgender women included, 2.5% had undergone orchiectomy, and 524 (34.2%) had any hormones within target concentrations. Median (interquartile range) E2 and TT concentrations at baseline were 29 (14.3-45.3) pg/mL and 298.5 (22-646) ng/dL, respectively. Among those who had any hormones within target concentrations, 28 (1.8%), 11 (0.7%), and 485 (31.6%) had both hormones, only E2, and only TT within target concentrations, respectively. Among 1010 (65.8%) transgender women who had neither hormone within target concentrations, 989 (64.5%) and 21 (1.4%) had suboptimal and supraphysiological E2 concentrations, respectively. Among those who came to at least one follow-up visit (n=302), 165 (54.6%) transgender women managed to achieve or maintain either hormone within target concentrations. Conclusion: One-third of Thai transgender women who were using FHT had any hormones within target concentrations at baseline in this real-world setting study. Most transgender women who had neither hormone within target concentrations had suboptimal rather than supraphysiological E2 concentrations. More than half managed to achieve or maintain at least one hormone concentration within target concentrations at follow-up visits, suggesting a positive effect from attending a trans-led, integrated gender-affirming care and sexual health service.

Vibratory and plantar pressure stimulation: Steps to improve freezing of gait in Parkinson's disease.

INTRODUCTION: Freezing of gait (FOG) is a devastating symptom that develops in patients with advanced Parkinson's disease (PD) and is often unresponsive to pharmacological treatment. Recent research suggests that FOG may result from dysfunctional plantar peripheral sensory systems. The impact of combined plantar pressure and vibratory stimulation over vibratory or pressure alone on FOG remains unexplored. METHODS: PD patients with FOG were randomised into four groups and treated with combined vibratory and pressure stimulation, vibratory stimulation alone, pressure stimulation alone, or controls (no stimulation). Vibratory stimulation targeted both Achilles' tendons. Simultaneous bilateral pressure stimulation was applied to the first hallux, first metatarsal bone, and the sole. The primary outcome included normalized percent changes in percent FOG measured both pre- and immediately post-stimulation. Other outcomes including clinical rating scale, response to questionnaires, number and duration of freezing episodes, and spatiotemporal gait parameters at pre- and freezing episodes were also explored. RESULTS: Sixty PD patients participated in the study. Patients who were treated with combined vibratory and pressure stimulation responded with significant decreases in normalized percent changes of percent FOG (62.75 ± 25.54%, p < 0.001) compared with those treated with vibration alone (11.38 ± 8.29%, p < 0.001), pressure alone (15.15 ± 16.18%, p < 0.001), or controls (8.59 ± 16.85%, p < 0.001). CONCLUSION: Our study demonstrated the benefit of combined vibratory and pressure stimulation on FOG suggesting that this strategy might be developed as a novel treatment modality for PD patients with FOG.

Short Communication: Incidence and Risk Factors of Ischemic Stroke and Transient Ischemic Attack Among People Living with HIV: A Longitudinal Cohort Study.

People living with HIV (PLWH) have higher ischemic cerebrovascular disease rates than HIV-negative individuals. We aimed to determine the incidence and risk factors of ischemic stroke (IS) and transient ischemic attack (TIA) among Thai PLWH. Data from adults living with HIV who were enrolled in a prospective HIV-NAT 006 cohort in Bangkok, Thailand, from 1996 to 2020 were included in the analysis. The primary endpoint was first-ever IS or TIA. Among 2020 PLWH included in the analysis, 16 (0.8%) developed first-ever IS/TIA over 23,579 person-years (incidence: 0.7 per 1,000 person-years [95% confidence interval {CI} 0.4-1.1]). Median CD4 cell counts before developing IS/TIA was 480 cells/mL and 87.5% were virologically suppressed. In multivariate models, hypertension was the only factor significantly associated with IS/TIA incidence (adjusted subhazard ratio 4.4; 95% CI 1.2-15.6, p = .02). The incidence of IS/TIA was low among well-suppressed Thai PLWH. Traditional risk factors, particularly hypertension, still play an essential role in developing IS/TIA.

Acceptability and satisfaction towards self-collection for chlamydia and gonorrhoea testing among transgender women in Tangerine Clinic, Thailand: shifting towards the new normal.

INTRODUCTION: Provider-collected swabs are an unappealing procedure for many transgender women and may have led to suboptimal rates of Chlamydia trachomatis (CT) and Neisseria gonorrhoeae (NG) testing. Self-collection for CT/NG testing is recommended for men who have sex with men. However, the information on acceptability and clinical performance to support a recommendation for transgender women is lacking. We aimed to determine the acceptability and satisfaction towards self-collection for CT/NG testing among Thai transgender women. METHODS: Thai transgender women who attended Tangerine Clinic (a transgender-led, integrated, gender-affirming care and sexual health services clinic in Bangkok, Thailand) between May and July 2020 and had condomless sexual intercourse within the past six months were offered to collect urine and perform self-swabs of pharyngeal, rectal, and if applicable, neovaginal compartments for pooled nucleic acid amplification testing for CT/NG infections. Participants received a diagram, video and oral instructions about how to perform self-collection procedure. Those who accepted self-collection were also offered to receive provider collection to evaluate the performance between the two methods. Self-administered questionnaires were used to assess satisfaction. RESULTS: Among 216 transgender women enrolled, 142 (65.7%) accepted self-collection. All who accepted had pharyngeal, rectal and urine samples collected. Of 31 transgender women who had undergone genital surgery, 28 (90.3%) accepted neovaginal self-swab. The acceptance rate increased from 46.2% in May to 84.5% in July 2020. One participant had an invalid result. All transgender women who accepted self-collection could perform it without assistance, and 82.8% were highly satisfied with the method. None reported dissatisfaction. Due to the COVID-19 pandemic, provider collection services were discontinued early, and only eight transgender women were able to perform both methods for performance evaluation. The performance agreement was 100%. CONCLUSIONS: Thai transgender women had high acceptability and satisfaction towards self-collection for CT/NG testing. The performance was promising compared to provider collection. Our results support the implementation of self-collection to the sexually transmitted infection services, particularly during the COVID-19 pandemic where physical distancing is the new normal. A larger study is warranted to determine the performance of self-collection for CT/NG testing in each anatomical compartment and confirm the performance between self-collection and provider collection.

Short Communication: Ischemic Stroke Subtypes Among Thai HIV-Infected Patients: A 12-Year Retrospective Study.

Traditional vascular risk factors and HIV-related factors can contribute to higher prevalence of ischemic stroke (IS) among HIV-infected patients. Understanding the underlying mechanism of IS could lead to proper management and prognosis. We aimed to determine the prevalence of IS subtypes among HIV-infected patients who were hospitalized due to IS. Medical records of patients who were hospitalized at the King Chulalongkorn Memorial Hospital, Bangkok, Thailand, between 2008 and 2019 due to first-ever IS with documented HIV infection were retrospectively analyzed. IS subtypes were classified according to the Trial of Org 10172 in Acute Stroke Treatment (TOAST) classification. Among 6,952 patients who were hospitalized due to IS, 50 [0.7% (95% confidence interval: 0.5-1.0)] were HIV-infected patients and were included in the analysis. Common traditional stroke risk factors were dyslipidemia (62%), smoking (55.3%), hypertension (52%), and alcohol consumption (45%). The median (interquartile range) CD4 cell count was 294.5 (186-485) cells/mL and 74% were on antiretroviral therapy. The most common etiology of IS was small vessel occlusion (SVO) (48%), followed by stroke of undetermined etiology (UD) (26%), and stroke of other determined etiology (OD) (14%). Among patients with OD, 5 of 7 were from infectious-related cause. Virologically unsuppressed group had significantly higher proportion of OD (33.3% vs. 3.6%), UD (38.9% vs. 17.9%), and lower proportion of SVO (22.2% vs. 60.7%) based on TOAST classification compared with virologically suppressed group (p = .01). SVO was the most common cause of IS among HIV-infected patients and was more likely to occur among virologically suppressed group, suggesting that traditional vascular risk factors may play a larger role in developing IS. OD was more likely to occur among virologically unsuppressed group, most of which were infectious-related cause.

Drug-drug Interactions Among Thai Transgender Women Living with Human Immunodeficiency Undergoing Feminizing Hormone Therapy and Antiretroviral Therapy: The iFACT Study.

BACKGROUND: Drug-drug interactions between feminizing hormone therapy (FHT) and antiretroviral therapy (ART) are a major concern among transgender women (TGW), which may lead to suboptimal ART adherence and inappropriate FHT dosage. To evaluate potential drug-drug interactions between FHT and ART, we performed intensive measurements of the pharmacokinetic (PK) parameters of blood tenofovir (TFV), efavirenz (EFV), and estradiol (E2). METHODS: Twenty TGW with newly diagnosed human immunodeficiency virus (HIV) infection were enrolled. FHT (E2 valerate 2 mg/d and cyproterone acetate 25 mg/d) was prescribed at baseline until week 5 and restarted at week 8. ART (TFV disoproxil fumarate/emtricitabine/EFV at 300/200/600 mg) was initiated at week 3. The E2 PK parameters were measured intensively at weeks 3 (without ART) and 5 (with ART), and TFV and EFV PK parameters were measured intensively at weeks 5 (with FHT) and 8 (without FHT). RESULTS: The median (interquartile range) age and body mass index were 25.5 (22.5-31.0) years and 20.6 (19.3-23.1) kg/m2, respectively. The differences in geometric mean ratios between weeks 3 and 5 were as follows for E2 area under the curve, maximum concentration, and concentration at 24 hours (C24), respectively: 0.72 (90% confidence interval, .64-.81; P < .001), 0.81 (.72-.92; P = .006), and 0.64 (.50-.83; P = .004). The differences in geometric mean ratios between weeks 5 and 8 were as follows for TFV AUC, TFV C24, and EFV C24: 0.86 (90% confidence interval, .80-.93; P = .002), 0.83 (.75-.93; P = .006), and 0.91 (.85-.97; P = .02). CONCLUSIONS: Among HIV-positive TGW, E2 PK parameters were significantly lower in the presence of TFV disoproxil fumarate/emtricitabine/EFV, and some TFV and EFV PK parameters were lower in the presence of FHT. Further studies should determine whether these reductions are clinically significant and whether they occur with other FHT or ART regimens.

Short Communication: Carotid Intima-Media Thickness Is Not Associated with Neurocognitive Impairment Among People Older than 50 Years With and Without HIV Infection from Thailand.

Neurocognitive impairment (NCI) contributes to poor quality of life among HIV-positive individuals. Cardiovascular risk factors, including the predictor of subclinical atherosclerosis, carotid intima-media thickness (cIMT), are reported to be associated with NCI. Data on NCI and its association with cIMT among HIV positive are limited, especially in Asian populations. We aimed to determine the prevalence of NCI and its association with cIMT among HIV-positive and HIV-negative aging Thai individuals. Cognitive performance was evaluated by the Thai version of Montreal Cognitive Assessment (MoCA) with a cutoff of <25/30 for diagnosis of NCI. Depression was evaluated by PHQ-9 Patient Depression Questionnaire, with scores ≥5 indicating depression. cIMT measurement was performed by experienced neurologists, and abnormal cIMT was defined as cIMT ≥0.9 mm or presence of carotid plaques. Among 340 well suppressed and aging HIV-positive and 102 HIV-negative matched participants, the median age (interquartile range) was 55 (52-59) years and 61.5% were males. For HIV positive group, the median duration on antiretroviral therapy was 18.3 years with median CD4 of 615.5 cells/mm3, and 97.4% had current plasma HIV RNA <50 copies/mL. The most common antiretroviral agents used were tenofovir disoproxil fumarate (76.8%), lamivudine (70.3%), efavirenz (26.7%), and emtricitabine (23.8%). HIV-positive and HIV-negative participants performed comparably between each domain and had comparable prevalence of NCI (59.4% vs. 61.7%, p = .69). However, the HIV-positive group had a high prevalence of depression (24.71% vs. 13.73%, p = .019). HIV-positive status [adjusted odd ratio (aOR) 0.91; 95% confidence interval (CI) 0.57-1.47, p = .71] and cIMT (aOR 1.17; 95% CI 0.77-1.79, p = .47) were not significantly associated with NCI. Given the high prevalence of NCI and depression among aging HIV-positive individuals, routine screening for NCI and depression should be integrated into the HIV care services.

Low CD4 Cell Counts Are Associated with Carotid Plaque and Intima-Media Thickness in Virologically Suppressed HIV-Infected Asians Older Than 50 Years.

Information about the prevalence, and risk factors for subclinical atherosclerosis in an Asian HIV-infected population is limited. Carotid intima-media thickness (cIMT) is one predictor for the risk of cardiovascular disease (CVDs) and mortality. We evaluated the prevalence and risk factors related to carotid atherosclerosis among well-suppressed HIV-infected adults receiving long-term ART from Thailand. This was a cross-sectional study of HIV-infected adults >50 years of age and free from CVDs from Thailand during 1 March 2016 and 30 May 2017. Ultrasonography of the carotid was performed and read by cIMT experienced neurologists who were blinded from the patient care. Subclinical atherosclerosis was defined by carotid plaque or cIMT of the common carotid artery (CCA) >0.9 mm. Totally 316 HIV-infected adults (61% males) were included. Median age was 54.4 years and 15.8% were diabetic, 40.2% had hypertension, and 12.7% were current smokers. The median duration of ART was 16.3 years and 32% were currently on boosted protease inhibitor. The mean overall cIMT of the common carotid arteries were 0.63 (IQR 0.55-0.72) mm. Men had higher cIMT than women, 0.64 (IQR 0.56-0.76) vs. 0.60 (IQR 0.53-0.70), p = .03. Overall, 3.8% had cIMT >0.9 mm and 24.4% had carotid plaque. From the multivariate logistic regression analysis, age per 1 year increase [odds ratio (OR) 1.06; 95% confidence interval (CI) 1.003-1.12; p = .04] and nadir CD4 < 200 cells/mm3 (OR 1.8; 95%CI 1.02-3.18, p = .04) were significantly associated with subclinical atherosclerosis. High-sensitivity C-reactive protein was not associated with subclinical atherosclerosis. In this well-suppressed HIV-infected Aging Asian cohort with relatively low prevalence of current smokers, 26.9% of them had subclinical atherosclerosis. Advanced age and low nadir CD4 cell count were significantly associated with subclinical atherosclerosis. Given that approximately a quarter of the patients had carotid plaques, longitudinal studies to evaluate the development of future overt coronary artery disease and stroke are warranted.

Drug-drug interactions between feminizing hormone therapy and pre-exposure prophylaxis among transgender women: the iFACT study.

INTRODUCTION: Concerns over potential drug-drug interactions (DDI) between feminizing hormone therapy (FHT) and pre-exposure prophylaxis (PrEP) have hampered uptake and adherence of PrEP among transgender women (TGW). To determine DDI between FHT and PrEP, we measured the pharmacokinetic (PK) parameters of blood plasma estradiol (E2) and tenofovir (TFV) in Thai TGW. METHODS: Twenty TGW who never underwent orchiectomy and had not received injectable FHT within six months were enrolled between January and March 2018. FHT (E2 valerate and cyproterone acetate) were prescribed to participants at baseline until week 5, and then from week 8 until the end of study. Daily PrEP (tenofovir disoproxil fumarate/emtricitabine) was initiated at week 3 and continued without interruption. Intensive E2 PK parameters and testosterone concentration at 24 hours (C24 ) were measured at weeks 3 (without PrEP) and 5 (with PrEP), and intensive TFV PK parameters were measured at weeks 5 (with FHT) and 8 (without FHT). RESULTS: Median (interquartile range) age, body mass index, and creatinine clearance were 21.5 (21-26) years, 20.6 (19.0-22.4) kg/m2 , and 116 (101-126.5) mL/min, respectively. The geometric mean (%CV) of area under curve from time zero to 24 hours (AUC0-24 ), maximum concentration (Cmax ), and C24 of E2 at weeks 3 and 5 were 775.13 (26.2) pg h/mL, 51.47 (26.9) pg/mL, and 15.15 (42.0) pg/mL; and 782.84 (39.6), 55.76 (32.9), and 14.32 (67.4), respectively. The geometric mean (%CV) of TFV AUC0-24 , Cmax , and C24 at weeks 5 and 8 were 2242.1 (26.5) ng h/mL, 353.9 (34.0) ng/mL, and 40.9 (31.4) ng/mL; and 2530.2 (31.3), 311.4 (30.0), and 49.8 (29.6), respectively. The geometric mean of TFV AUC0-24 and C24 at week 5 were significantly less than that at week 8 by 12% (p = 0.03) and 18% (p < 0.001), respectively. There were no significant changes in E2 PK parameters and median C24 of bioavailable testosterone between week 3 and week 5. CONCLUSIONS: Our study demonstrated lower blood plasma TFV exposure in the presence of FHT, suggesting that FHT may potentially affect PrEP efficacy among TGW; but E2 exposure was not affected by PrEP. Further studies are warranted to determine whether these reductions in TFV are clinically significant. Clinical Trial Number: NCT03620734.

Correlations of chlamydia and gonorrhoea among pharyngeal, rectal and urethral sites among Thai men who have sex with men: multicentre community-led test and treat cohort in Thailand.

OBJECTIVE: Routine screening for Chlamydia trachomatis (CT) and Neisseria gonorrhoeae (NG) infections in sexually exposed anatomical sites may be challenging in resource-limited settings. The objective of this study was to determine the proportion of missed CT/NG diagnoses if a single anatomical site screening was performed among men who have sex with men (MSM) by examining the pattern of anatomical sites of CT/NG infections. METHODS: Thai MSM were enrolled to the community-led test and treat cohort. Screening for CT/NG infections was performed from pharyngeal swab, rectal swab and urine using nucleic acid amplification testing. The correlations of CT/NG among the three anatomical sites were analysed. RESULTS: Among 1610 MSM included in the analysis, 21.7% had CT and 15.5% had NG infection at any anatomical site. Among those tested negative for CT or NG infection at either pharyngeal, rectal or urethral site, 8%-19% had CT infection and 7%-12% had NG infection at the remaining two sites. Of the total 349 CT infections, 85.9%, 30.6% and 67.8% would have been missed if only pharyngeal, rectal or urethral screening was performed, respectively. Of the total 249 NG infection, 55.7%, 39.6% and 77.4% would have been missed if only pharyngeal, rectal or urethral screening was performed, respectively. The majority of each anatomical site of CT/NG infection was isolated to their respective site, with rectal site having the highest proportion of isolation: 78.9% of rectal CT and 62.7% of rectal NG infection. CONCLUSIONS: A high proportion of CT/NG infections would be missed if single anatomical site screening was performed among MSM. All-site screening is highly recommended, but if not feasible, rectal screening provides the highest yield of CT/NG diagnoses. Effort in lowering the cost of the CT/NG screening test or developing affordable molecular technologies for CT/NG detection is needed for MSM in resource-limited settings. TRIAL REGISTRATION NUMBER: NCT03580512; Results.

High burden of chlamydia and gonorrhoea in pharyngeal, rectal and urethral sites among Thai transgender women: implications for anatomical site selection for the screening of STI.

OBJECTIVE: Comprehensive data on Chlamydia trachomatis (CT) and Neisseria gonorrhoeae (NG) infections to guide screening services among transgender women (TGW) are limited. We studied the burden of CT/NG infections in pharyngeal, rectal and urethral sites of Thai TGW and determined missed CT/NG diagnoses if selected site screening was performed. METHODS: Thai TGW were enrolled to the community-led test and treat cohort. CT/NG screening was performed from pharyngeal swab, rectal swab and urine using nucleic acid amplification test. CT/NG prevalence in each anatomical site was analysed, along with the relationships of CT/NG among the three anatomical sites. RESULTS: Of 764 TGW included in the analysis, 232 (30.4%) had CT/NG infections at any anatomical site, with an overall incidence of 23.7 per 100 person-years. The most common CT/NG infections by anatomical site were rectal CT (19.5%), rectal NG (9.6%) and pharyngeal NG (8.1%). Among 232 TGW with CT/NG infections at any anatomical site, 22%-94.4% of infections would have been missed if single anatomical site testing was conducted, depending on the selected site. Among 668 TGW who tested negative at pharyngeal site, 20.4% had either rectal or urethral infections. Among 583 TGW who tested negative at the rectal site, 8.7% had either pharyngeal or urethral infections. Among 751 TGW who tested negative at the urethral site, 19.2% had either pharyngeal or rectal infections. CONCLUSION: Almost one-third of Thai TGW had CT/NG infections. All-site screening is highly recommended to identify these infections, but if not feasible rectal screening provides the highest yield of CT/NG diagnoses. Affordable molecular technologies and/or CT/NG screening in pooled samples from different anatomical sites are urgently needed. TRIAL REGISTRATION NUMBER: NCT03580512.

Changes in risk behaviors among Thai men who have sex with men and transgender women enrolled in the test and treat cohort.

The test-and-treat approach has the potential to reduce high-risk sexual behaviors by linking high-risk individuals to health education, although this has not been proven yet. We used longitudinal data from the Test and Treat Demonstration Project among Thai men who have sex with men (MSM) and transgender women (TGW) who were not known to be HIV-positive to analyze changes in risk behaviors during the 24-month study period categorized by three groups: HIV-negative without seroconversion, seroconverters, and HIV-positive at enrollment. Five binary risk behavior outcomes - laboratory-diagnosed sexually transmitted infections (STIs); multiple sexual partners, unprotected anal intercourse, self-perceived HIV risk, and amphetamine-type stimulants use in the past month - were assessed. Among 689 participants, with a mean (SD) age of 23.1 (6.2) years, 165 participants were diagnosed with HIV: 115 at enrollment and 50 with seroconversions. HIV-positive participants at enrollment showed significant reductions in all five behavioral risk outcomes. Seroconverters demonstrated higher risks at enrollment than HIV-negative participants, and continued to practice high-risk behaviors even after seroconversion despite a significant reduction in self-perceived moderate-to-high HIV risk. Continuation of risk behaviors among seroconverters could negatively affect the ending AIDS goal, thus the integration of other effective preventive measures into HIV/STIs management programs are needed.

Comparable carotid intima-media thickness among long-term virologically suppressed individuals with HIV and those without HIV in Thailand.

OBJECTIVES: This study compared the carotid intima-media thickness (cIMT) among well suppressed adult participants living with HIV and adults without HIV, aged >45 years. METHODS: A cross-sectional, age and sex-matched study was conducted at two sites in Thailand: King Chulalongkorn Memorial Hospital (KCMH) and HIV-NAT. All participants had no evidence of coronary artery disease (CAD). Ultrasonography of the carotid artery was measured by one well-trained neurologist who was blinded to the participants' care. The primary endpoint was the difference in cIMT between participants with HIV and controls without HIV. Prevalence and predictive risk of cIMT≥0.9 mm were determined. RESULTS: Of 90 individuals, 60 were living with HIV. The overall median (IQR) age was 54.1 (52-60) years and 53.3% were male. For the group with HIV, the median duration of ART was 15 years and 33% were on boosted PIs. Compared to controls without HIV, the group with HIV had a higher proportion of hypertriglyceridaemia (48.3% vs 26.7%, P=0.049) but the median overall cIMT of the common carotid arteries (0.665 mm vs 0.649 mm, P=0.277) and serum high-sensitivity C-reactive protein (hs-CRP) (1.59 mg/dL vs 1.46 mg/dL, P=0.325) were not different. Hs-CRP was not correlated with cIMT ≥0.9 mm. However, carotid plaques (n=6) were found only among the group with HIV. From the multivariate analysis, only male sex and hypertension were significantly associated with cIMT ≥0.9 mm. CONCLUSIONS: Well-controlled and long-term treated participants living with HIV had comparable cIMT to Thai adults without HIV. Monitoring for progression of cIMT, carotid plaques and cardiovascular disease in this population is warranted to guide continued management.

High subsequent and recurrent sexually transmitted infection prevalence among newly diagnosed HIV-positive Thai men who have sex with men and transgender women in the Test and Treat cohort.

We determined subsequent and recurrent sexually transmitted infections (STIs) among men who have sex with men (MSM) and transgender women (TGW) in the Test and Treat cohort. Thai MSM and TGW adults with previously unknown HIV status were enrolled and tested for HIV. Chlamydia trachomatis (CT), Neisseria gonorrhoeae (NG), and syphilis were tested at baseline, month 12, and month 24 to identify subsequent STIs (any STIs diagnosed after baseline) and recurrent STIs (any subsequent STIs diagnosed among those with positive baseline STIs). Among 448 participants, 17.8% were HIV-positive, the prevalence of subsequent STIs and recurrent STIs was 42% (HIV-positive versus HIV-negative: 66.3% versus 36.7%, p < 0.001) and 62.3% (81% versus 52.5%, p < 0.001), respectively. Common subsequent STIs by anatomical site were rectal CT infection (21.7%), rectal NG infection (13.8%), pharyngeal NG infection (13.1%), and syphilis (11.9%). HIV-positive status was associated with both subsequent STIs (adjusted hazard ratio [aHR] 2.38; 95%CI 1.64-3.45, p < 0.001) and recurrent STIs (aHR 1.83; 95%CI 1.16-2.87, p = 0.01). The results show that newly diagnosed HIV-positive MSM and TGW were at increased risk of STIs despite being in the healthcare system. STI educational counseling is necessary to improve STI outcomes among MSM and TGW in both HIV prevention and treatment programs.