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HCV RNA test determines current active infection and is a requirement prior to initiating HCV treatment. We investigated trends and factors associated with post‐diagnosis HCV RNA testing rates prior to HCV treatment, and risk factors for first positive HCV RNA among people living with HIV (PLHIV) with HCV in the Asia‐Pacific region. PLHIV with positive HCV antibody and in follow‐up after 2010 were included. Patients were considered HCV‐antibody positive if they ever tested positive for HCV antibody (HCVAb). Repeated measures Poisson regression model was used to analyse factors associated with post‐diagnosis HCV RNA testing rates from positive HCVAb test. Factors associated with time to first positive HCV RNA from positive HCVAb test were analysed using Cox regression model. There were 767 HCVAb positive participants included (87% from LMICs) of whom 11% had HCV RNA tests. With 163 HCV RNA tests post positive HCVAb test, the overall testing rate was 5.05 per 100 person‐years. Factors associated with increased testing rates included later calendar years of follow‐up, HIV viral load ≥1000 copies/mL and higher income countries. Later calendar years of follow‐up, ALT >5 times its upper limit of normal, and higher income countries were associated with shorter time to first positive HCV RNA test. Testing patterns indicated that uptake was predominantly in high income countries possibly due to different strategies used to determine testing in LMICs. Expanding access to HCV RNA, such as through lower‐cost point of care assays, will be required to achieve elimination of HCV as a public health issue. [ABSTRACT FROM AUTHOR]

Sofosbuvir/Velpatasvir (SOF/VEL) is a combination drug used for chronic hepatitis C (HCV) infection. However, limited information exists regarding the pharmacokinetics of SOF/VEL and its metabolites in hemodialysis patients. We conducted a prospective investigation of the pharmacokinetic parameters of SOF/VEL after a single dose of SOF/VEL (400/100 mg) on days with and without dialysis in 12 Thai hemodialysis patients with chronic HCV infection, who had been undergoing hemodialysis for a duration of 0.5–20 years. Blood samples were collected before dose (0) and 0.5, 1.0, 2.0, 2.5, 3.0, 3.5, 4.0, 5.0, 6.0, 8.0, and 12.0 h after dose. Dialysate samples were also collected before dose (0) and 1.0, 2.0, 3.0, and 4.0 h after dose. Plasma and dialysate samples were quantified for SOF and its metabolite, GS‐331007, and VEL concentrations using a fully validated LCMS technique. In addition, a preliminary efficacy study was conducted using the proposed SOF/VEL dose reduction regimen in all patients. No differences in SOF/VEL PK parameters between on‐ and off‐dialysis studies. On the contrary, GS‐331007 exhibited a 30% reduction in the area under the plasma concentration–time curve from time 0 to 24 h (AUC0‐24h) on dialysis days compared with non‐dialysis days (AUC0‐24h ratio 0.68 vs. 1.04, respectively). The dialysis clearance of SOF and GS‐331007 was 9.35 (8.72–15.11) and 8.89 (8.52–14.07) mL/min, respectively. Subsequently, an alternate‐day regimen of SOF/VEL (400/100 mg) was administered for 12 weeks, resulting in an undetectable plasma HCV viral load without side effects. Further clinical studies are warranted to validate the efficacy and safety of our proposed dose reduction regimen. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Objective: To characterize its dose‐response relationship, BI 655064 (an anti‐CD40 monoclonal antibody) was tested as an add‐on to mycophenolate and glucocorticoids in patients with active lupus nephritis (LN). Methods: A total of 121 patients were randomized (2:1:1:2) to receive placebo or BI 655064 120, 180, or 240 mg and received a weekly loading dose for 3 weeks followed by dosing every 2 weeks for the 120 and 180 mg groups, and 120 mg weekly for the 240 mg group. The primary endpoint was complete renal response (CRR) at week 52. Secondary endpoints included CRR at week 26. Results: A dose‐response relationship with CRR at week 52 was not shown (BI 655064 120 mg, 38.3%; 180 mg, 45.0%; 240 mg, 44.6%; placebo, 48.3%). At week 26, 28.6% (120 mg), 50.0% (180 mg), 35.0% (240 mg), and 37.5% (placebo) achieved CRR. The unexpected high placebo response prompted a post hoc analysis evaluating confirmed CRR (cCRR, at weeks 46 and 52). cCRR was achieved in 22.5% (120 mg), 44.3% (180 mg), 38.2% (240 mg), and 29.1% (placebo) of patients. Most patients reported ≥1 adverse event (BI 655064, 85.7–95.0%; placebo, 97.5%), most frequently infections and infestations (BI 655064 61.9–75.0%; placebo 60%). Compared with other groups, higher rates of serious (20% vs. 7.5–10%) and severe infections (10% vs. 4.8–5.0%) were reported with 240 mg BI 655064. Conclusion: The trial failed to demonstrate a dose‐response relationship for the primary CRR endpoint. Post hoc analyses suggest a potential benefit of BI 655064 180 mg in patients with active LN. [ABSTRACT FROM AUTHOR]

Introduction: A change in terminology from fatty liver disease to metabolic‐associated fatty liver disease (MAFLD), along with modified diagnostic criteria, was proposed in 2020, and data regarding MAFLD burden in people living with HIV are limited. We investigated associations between MAFLD and immune activation, cardiovascular disease (CVD) risks including epicardial fat volume, and steatohepatitis in an Asian cohort. Methods: We evaluated CVD risk (epicardial fat tissue, coronary artery calcium [CAC] score, and 10‐year atherosclerotic CVD [ASCVD] score) in people living with HIV aged >50 years. Individuals with excessive alcohol consumption and viral hepatitis infections were excluded. MAFLD diagnosis was based on 2020 International Consensus criteria. Non‐alcoholic steatohepatitis (NASH) with significant activity and liver fibrosis was defined as FibroScan‐aspartate aminotransferase (FAST) score ≥0.67 and >0.35. Multivariate logistic regression models were used to investigate factors associated with MAFLD and NASH with significant activity and liver fibrosis. Results: The median age was 54 years (interquartile range [IQR] 52–60) and current CD4 count was 613 (IQR 467–804) cells/mm3. A total of 37% were female, and most (98%) people living with HIV were virally suppressed. The prevalence of MAFLD and non‐alcoholic fatty liver disease was 35% and 38%, respectively. In multivariate analyses, higher body mass index, albumin, epicardial fat volume, and liver stiffness were significantly associated with MAFLD. A higher CD4/CD8 ratio was associated with a lower risk of MAFLD. People with HIV with MAFLD had higher odds of having NASH with significant activity and liver fibrosis (adjusted odds ratio 3.3; 95% confidence interval 1.6–6.6), and similar associations were also observed among different MAFLD categories. Conclusions: The complex relationship between MAFLD and immune activation, steatohepatitis, and epicardial fat tissue suggests an increased risk of advanced liver disease and CVDs beyond the traditional risk factors in people living with HIV with fatty liver disease. [ABSTRACT FROM AUTHOR]

Objectives: Data on switching to bictegravir, emtricitabine, and tenofovir alafenamide (B/F/TAF) in virologically suppressed Asian people living with HIV are limited. We performed a pooled analysis of virologically suppressed Asian participants from three international phase III trials to evaluate the efficacy and safety of switching to B/F/TAF. Methods: Virologically suppressed people living with HIV were randomized to switch to B/F/TAF or to stay on baseline regimens. The primary endpoint was the proportion of participants with plasma HIV‐1 RNA ≥50 copies/ml at week 48. We analysed the incidence of adverse events (AEs), laboratory abnormalities, and changes in relevant tolerability parameters through 48 weeks. Results: Overall, 136 Asian participants were included. The proportions of participants with plasma HIV‐1 RNA ≥50 copies/ml at week 48 were low in both arms (0% for B/F/TAF vs 1.4% for those who stayed on baseline regimens). Those who switched to B/F/TAF had virological suppression rates similar to those who stayed on baseline regimens (100% vs 95.9%, p = 0.2485), with no treatment‐emergent resistance. Drug‐related AEs occurred in three participants in each arm; none were serious. No participants discontinued the study drug because of AEs, and no deaths were observed. No significant differences were observed between the arms in the median changes in estimated glomerular filtration rate, body weight, and most lipid parameters. Switching from tenofovir disoproxil fumarate‐containing regimens to B/F/TAF resulted in a significant decrease in tubular proteinuria compared with those who stayed on baseline regimens (p < 0.01). Conclusions: Virologically suppressed Asian people living with HIV who switched to B/F/TAF maintained 100% virological suppression at week 48, with no treatment‐emergent drug resistance and safety profiles comparable to those seen in people who stayed on baseline regimens. Clinical Trial Number: ClinicalTrials.gov (NCT02603120, NCT02652624, and NCT02603107). [ABSTRACT FROM AUTHOR]

Background: Non‐Asian body mass index (BMI) classifications are commonly used as a risk factor for high fasting blood glucose (FBG). We investigated the incidence and factors associated with high FBG among people living with HIV in the Asia‐Pacific region, using a World Health Organization BMI classification specific to Asian populations. Methods: This study included people living with HIV enrolled in a longitudinal cohort study from 2003 to 2019, receiving antiretroviral therapy (ART), and without prior tuberculosis. BMI at ART initiation was categorized using Asian BMI classifications: underweight (<18.5 kg/m2), normal (18.5–22.9 kg/m2), overweight (23–24.9 kg/m2), and obese (≥25 kg/m2). High FBG was defined as a single post‐ART FBG measurement ≥126 mg/dL. Factors associated with high FBG were analyzed using Cox regression models stratified by site. Results: A total of 3939 people living with HIV (63% male) were included. In total, 50% had a BMI in the normal weight range, 23% were underweight, 13% were overweight, and 14% were obese. Median age at ART initiation was 34 years (interquartile range 29–41). Overall, 8% had a high FBG, with an incidence rate of 1.14 per 100 person‐years. Factors associated with an increased hazard of high FBG included being obese (≥25 kg/m2) compared with normal weight (hazard ratio [HR] = 1.79; 95% confidence interval [CI] 1.31–2.44; p < 0.001) and older age compared with those aged ≤30 years (31–40 years: HR = 1.47; 95% CI 1.08–2.01; 41–50 years: HR = 2.03; 95% CI 1.42–2.90; ≥51 years: HR = 3.19; 95% CI 2.17–4.69; p < 0.001). Conclusion: People living with HIV with BMI >25 kg/m2 were at increased risk of high FBG. This indicates that regular assessments should be performed in those with high BMI, irrespective of the classification used. [ABSTRACT FROM AUTHOR]

The kidney is a notable site of glycolysis, gluconeogenesis, and fatty acid oxidation. Loss of a kidney after kidney donation might, therefore, affect the glucose and lipid metabolism of the donors. This matched cohort study investigated the effect of nephrectomy on glucose and lipid metabolisms using Bayesian hypothesis testing. There were 77 pairs of matched donor‐control pairs in the present study. Clinical and laboratory data of the participants, at baseline and 1‐year, were extracted from electronic medical records. Comparisons between donor and control groups were performed using the Bayesian independent samples t‐test or Bayesian Mann–Whitney test. The Bayes Factor for alternative hypothesis over null hypothesis (BF10) was used to compare the two competing hypotheses. The BF10 of 3 or more was considered evidence for the alternative hypothesis. Comparing changes from baseline to 1‐year between donors and controls, the BF10 of triglycerides, high‐density lipoprotein cholesterol (HDL‐C), triglyceride‐glucose (TyG) index of insulin resistance, and estimated glomerular filtration rate (eGFR) were 7.95, 3.96, 30.13, and 1.32 x 1041, respectively signifying that the change of these variables in the donors differed from those in the controls (alternative hypothesis). Triglyceride, HDL‐C, and TyG index of the donors increased more than those of the controls while eGFR of the donor decreased more than that of the controls. Our data suggest that triglycerides and insulin resistance increase after donor nephrectomy. Kidney donors should be informed about these metabolic changes and should adhere to lifestyle recommendations that may mitigate insulin resistance. Summary at a Glance: This matched cohort study investigated the effect of kidney donation on glucose and lipid metabolisms using Bayesian hypothesis testing. Kidney donation increased triglyceride, high‐density lipoprotein cholesterol, and triglyceride‐glucose index of insulin resistance. These metabolic effects of kidney donation should be recognized and appropriately addressed. [ABSTRACT FROM AUTHOR]

Liver disease is a growing burden among people living with HIV (PLHIV) in resource‐limited settings. As an indicator of liver disease, risk factors of high alanine aminotransferase (ALT) and cirrhosis were assessed among PLHIV in the TREAT Asia HIV Observational Database (TAHOD). Patients on combination antiretroviral therapy (cART) with a pre‐cART ALT measurement and at least one follow‐up ALT measurement were included. Factors associated with high ALT (ALT levels > 5 times its upper limit of normal) were analyzed using repeated measure logistic regression over a 10‐year follow‐up period. Liver cirrhosis was defined as having an AST to Platelet Ratio Index score > 1.5, fibrosis‐4 score > 3.25, or a clinical diagnosis of cirrhosis. Cox regression analysis stratified by site was used to analyze factors associated with cirrhosis among those in follow‐up after 2015. Of 5182 patients, 101 patients (1.9%) had high ALT levels with hepatitis C virus (HCV) antibody positive (odds ratio [OR]: 4.98, 95% confidence interval [CI]: 2.82–8.77, p < 0.001) and ever high alcohol consumption (OR: 2.33, 95% CI: 1.00–5.46, p = 0.050) as likely factors. Among 6318 PLHIV in the liver cirrhosis analysis, 151 (2%) developed cirrhosis (incidence rate = 0.82 per 100 person‐years). Those HCV‐antibody positive (hazard ratio [HR]: 5.54, 95% CI: 3.75–8.18, p < 0.001) and had high alcohol consumption (HR: 2.06, 95% CI: 1.23–3.45, p = 0.006) were associated with liver cirrhosis. HCV‐antibody positive and high alcohol consumption are factors associated with high ALT. With raised ALT levels as a known factor associated with liver cirrhosis, greater efforts are required in managing ALT levels and reducing the risk of developing liver cirrhosis among those positive for HCV‐antibody and those who consume alcohol. [ABSTRACT FROM AUTHOR]

Background: Although the prevalence and mortality of hepatitis is high in the Asia‐Pacific region, few studies are available on the diagnosis, treatment, and cure rates for viral hepatitis among people living with HIV in this area. This study aims to report the cascade of care (CoC) for hepatitis B (HBV) and C (HCV) among people living with HIV receiving combined antiretroviral therapy (ART). Methods: Patients enrolled in the TREAT Asia HIV Observational Database Low Intensity Transfer (TAHOD‐LITE) cohort, on ART, and with follow‐up data from 2010 to 2019 were included. Patients were determined as positive for HCV or HBV co‐infection if they ever tested positive for HCV antibody (anti‐HCV) or HBV surface antigen (HBsAg), respectively. Results: In total, 39% (8612/22 340) of the adult HIV cohort had undergone HBsAg testing, with 8% (672/8612) testing positive. HBV CoC demonstrated that 71% (474/672) of those with HBsAg positive results initiated treatment, 67% (318/474) of those on treatment had HBV DNA testing to evaluate treatment progression, and 18% (58/318) of those tested reached viral suppression. Of the cohort, 37% (8231/22 340) had anti‐HCV testing, of whom 10% (779/8231) tested positive. The HCV CoC showed that 68% (526/779) of those with positive anti‐HCV tests had HCV RNA tests, of whom 51% (267/526) had detectable HCV RNA. Among those with detectable HCV RNA, 65% (174/267) initiated HCV treatment. Of the 40% (69/174) who initiated HCV treatment, 90% (62/69) reached sustained virological response. Conclusion: Our findings identified less frequent testing in the healthcare system and limited access to treatment as gaps in the CoC for viral hepatitis. More routine HCV RNA and HBV DNA testing is required for patients with positive screening tests to identify those in need of treatment. [ABSTRACT FROM AUTHOR]

Relapsed or resistant lupus nephritis (LN) is considered a difficult‐to‐treat type of LN, and enteric‐coated mycophenolate sodium (EC‐MPS) has been used in this condition. Therapeutic drug monitoring using the area under the plasma mycophenolic acid concentration from 0 to 12 h postdose (MPA‐AUC0–12h) ≥45 μg.h/ml is a useful approach to achieve the highest efficiency. This study assessed EC‐MPS's pharmacokinetic (PK) and pharmacodynamic (PD) profiles and investigated an optimal level of the single time point of plasma MPA concentration. Nineteen biopsy‐proven patients with class III/IV LN received 1440 mg/day of EC‐MPS for 24 weeks. PK (maximum plasma MPA concentration [Cmax], time to Cmax, and MPA‐AUC0–12h) and PD (activity of inosine‐5′‐monophosphate dehydrogenase [IMPDH]) parameters were measured at weeks 2, 8, 16, and 24. We found that IMPDH activity decreased from baseline by 31–42% within 2–4 h after dosing, coinciding with the increased plasma MPA concentration. MPA‐AUC0–12h ≥45 μg.h/ml was best predicted by a single time point MPA concentration at C0.5, C2, C3, C4, and C8 (r2 = 0.516, 0.514, 0.540, 0.611, and 0.719, respectively), independent of dose, albumin, urine protein/creatinine ratio, and urinalysis. The MPA‐C0.5 cutoff of 2.03 g/ml yielded the highest overall sensitivity of 85% and specificity of 88.2% in predicting MPA‐AUC0–12h ≥45 μg.h/ml. A single timepoint of plasma MPA‐C0.5 ≥2.03 μg/ml may help guide EC‐MPS adjustment to achieve adequate drug exposure. Further study of EC‐MPS used to validate this cutoff is warranted. [ABSTRACT FROM AUTHOR]

Introduction: ACTG A5288 was a strategy trial conducted in diverse populations from multiple continents of people living with HIV (PLWH) failing second‐line protease inhibitor (PI)‐based antiretroviral therapy (ART) from 10 low‐ and middle‐income countries (LMICs). Participants resistant to lopinavir (LPV) and/or multiple nucleotide reverse transcriptase inhibitors started on third‐line regimens that included raltegravir (RAL), darunavir/ritonavir (DRV/r) and/or etravirine (ETR) according to their resistance profiles. At 48 weeks, 87% of these participants achieved HIV‐1 RNA ≤200 copies/ml. We report here long‐term outcomes over 144 weeks. Methods: Study participants were enrolled from 2013 to 2015, prior to the availability of dolutegravir in LMICs. "Extended Follow‐up" of the study started after the last participant enrolled had reached 48 weeks and included participants still on antiretroviral (ARV) regimens containing RAL, DRV/r and/or ETR at that time. RAL, DRV/r and ETR were provided for an additional 96 weeks (giving total follow‐up of ≥144 weeks), with HIV‐1 RNA measured at 48 and 96 weeks and CD4 count at 96 weeks after entry into Extended Follow‐up. Proportion of participants with HIV‐1 RNA ≤200 copies/ml was estimated every 24 weeks, using imputation if necessary to handle the different measurement schedule in Extended Follow‐up; mean CD4 count changes were estimated using loess regression. Results and Discussion: Of 257 participants (38% females), at study entry, median CD4 count was 179 cells/mm3, and HIV‐1 RNA was 4.6 log10 copies/ml. Median follow‐up was 168 weeks (IQR: 156–204); 15 (6%) participants were lost to follow‐up and 9 (4%) died. 27/246 (11%), 26/246 (11%) and 13/92 (14%) of participants who started RAL, DRV/r and ETR, respectively, discontinued these drugs; only three due to adverse events. 87%, 86%, 83% and 80% of the participants had HIV‐1 RNA ≤200 copies/ml at weeks 48, 96, 144 and 168 (95% CI at week 168: 74–85%), respectively. Mean increase from study entry in CD4 count at week 168 was 265 cells/mm3 (95% CI 247–283). Conclusions: Third‐line regimens comprising of RAL, DRV/r and/or ETR were very well tolerated and had high rates of durable virologic suppression among PLWH in LMICs who were failing on second‐line PI‐based ART prior to the availability of dolutegravir. [ABSTRACT FROM AUTHOR]

Aim: The incidences of osteoporosis, fracture and vascular calcification increase concordantly with the progression of chronic kidney disease (CKD). CKD‐mineral bone disease (CKD‐MBD) induced by hyperphosphatemia is a major pathophysiologic mechanism. The effects of phosphate binders on bone turnover biomarkers and bone mineral density (BMD) in haemodialysis patients are still inconclusive. Our aim is to demonstrate the effects of these phosphate binders on different aspects of CKD‐MBD. Methods: We conducted a prospective cohort of 65 haemodialysis patients to investigate the effect of 12‐month monotherapy of phosphate binders composing calcium‐based phosphate binders (CPB) or non‐calcium‐based phosphate binders (NCPB), including sevelamer and lanthanum, on bone turnover biomarkers and BMD changes. The performance of bone turnover biomarkers to predict low BMD was attentively determined. Results: When compared with CPB, NCPB use was associated with higher levels of bone turnover biomarkers. NCPB was also associated with lower BMD at lumbar and distal radius. Total procollagen type 1N‐terminal propeptide (P1NP), bone‐specific alkaline phosphatase (BALP), and tartrate‐resistant acid phosphatase 5b (TRAP5b) provided the best performance for diagnosing low BMD in haemodialysis patients. Conclusion: Switching from CPB to NCPB might increase bone biomarkers and prevent the development of adynamic bone disease. On the contrary, NCPB should be cautiously used in haemodialysis patients who already had low BMD. P1NP, BALP and TRAP5b could be used to guide the appropriate management, including anti‐resorptive and anabolic medications, and predict low BMD in haemodialysis patients treated with phosphate binders. SUMMARY AT A GLANCE: The effect of phosphate binders on bone biomarkers and bone mineral density (BMD) in haemodialysis patients is unestablished. This prospective study revealed that non‐calcium‐based phosphate binders were associated with higher bone turnover biomarkers compared with calcium‐based phosphate binders. Diagnostic power of each bone biomarker for low BMD was demonstrated. [ABSTRACT FROM AUTHOR]

Background: Despite the success of combination antiretroviral therapy (cART), cognitive impairment remains a problem for people living with HIV (PLWH), including those who are virologically suppressed. The presentation and course of cognitive impairment have changed significantly since the introduction of cART. We aimed to determine the trajectory of cognitive performance in a cohort of virologically suppressed aging PLWH. Method: Thai PLWH aged ≥50 years followed in the HIV‐NAT 006 cohort were enrolled during 2015‐2017 to assess cognitive performance using the Thai‐validated Montreal Cognitive Assessment (MoCA), a cutoff of ≥25 as normal. The follow‐up MoCA was consecutively performed since 2021. Participants who had plasma HIV RNA of ≤50 copies/mL and completed the follow‐up MoCA were included in the analysis. Changes in the MoCA scores were calculated between the two visits. Result: Among 181 eligible participants (69 [38.1%] female; mean [SD] age, 57.0 [5.7] years; 46 [25.4%] had education ≤6 years; mean duration of HIV infection, 18.0 [4.2] years), 104 (57.5%) had cognitive impairment at enrollment. There were statistically significantly higher proportion of female sex (45.2% vs 28.6%, p = 0.023) and participants who had education >6 years (85.6% vs 59.4%, p<0.001) among cognitively impaired (CI) than cognitively unimpaired (CU) participants. After mean 5.6 (0.4) years of follow‐up period, the mean difference of the MoCA score was ‐0.72 (95%CI ‐1.29 to ‐0.15, p = 0.01, d = 0.19) and there were statistically significant differences in the MoCA score changes between groups categorized by baseline cognitive performance (mean difference 3.25, 95%CI 2.09 to 4.41, p<0.001, after adjusting for sex assigned at birth, age, education levels, smoking status, depression, hypertension, and diabetes mellitus).The CU group showed a statistically significant decrease in the MoCA score (mean difference ‐2.58, 95%CI ‐3.26 to ‐1.90, p<0.001, d = 0.86), and 43/77 (55.8%) of CU participants developed cognitive impairment at follow‐up, while the CI group had comparable MoCA scores between the two visits (mean difference 0.65, p = 0.09) (figure). Conclusion: CU virologically suppressed PLWH demonstrated a statistically significant reduction in cognitive performance compared to their CI counterparts over time. Further studies on the underlying pathological mechanisms and implementation of cognitive care services among virologically suppressed PLWH are warranted. [ABSTRACT FROM AUTHOR]

Aim: Fibrosis regression has been observed in patients with chronic hepatitis C virus (HCV) infection treated with direct‐acting antivirals. This study was aimed at evaluating dynamic changes of serum Mac‐2‐binding protein glycosylation isomer (M2BPGi) in patients with HCV genotype 1 receiving elbasvir/grazoprevir. Methods: M2BPGi were serially measured at baseline, during and after therapy. Its diagnostic performance at baseline and sustained virological response at 24 weeks after treatment (SVR24) were compared with transient elastography (TE) and the aspartate aminotransferase/platelet ratio index (APRI) using magnetic resonance elastography (MRE) as a reference. Results: Overall, 60 HCV mono‐infected and 36 HCV/HIV co‐infected patients were included with SVR24 rates of 93.3% and 97.2%, respectively. At baseline, TE, M2BPGi and APRI were correlated with MRE (r = 0.788, r = 0.703 and r = 0.564, respectively, p < 0.001). The area under the receiver operator characteristics curves for TE, M2BPGi and APRI in differentiating significant fibrosis were 0.88 (95% confidence interval; 0.81–0.95, p < 0.001), 0.86 (0.79–0.94, p < 0.001) and 0.74 (0.64–0.83, p < 0.001), respectively. The corresponding figures for cirrhosis were 0.95 (0.90–1.00, p < 0.001), 0.96 (0.92–1.00, p < 0.001) and 0.88 (0.79–0.97, p < 0.001), respectively. Compared with baseline, all fibrosis markers significantly declined after achieving SVR24. The correlations of TE, M2BPGi and APRI with MRE at time of SVR24 were r = 0.587 (p < 0.001), r = 0.457 (p < 0.001) and r = 0.293 (p = 0.004), respectively. In multivariate analysis, high baseline alanine aminotransferase level, HCV mono‐infection and advanced fibrosis were factors associated with M2BPGi reduction. Conclusions: HCV eradication is associated with liver fibrosis improvement. M2BPGi has a better performance than APRI in monitoring liver fibrosis in patients treated with direct‐acting antivirals. This marker is applicable in resource‐limited settings where imaging‐based modalities are not widely accessible. [ABSTRACT FROM AUTHOR]

We report a case of COVID‐19 in kidney transplant patient in Thailand. A 58‐year‐old 2 years post–kidney transplant recipient, with maintenance immunosuppression of tacrolimus, mycophenolate mofetil (MMF), and prednisolone, presented with acute diarrhea which followed by fever on day 12. Symptoms of pneumonia together with lymphopenia from complete blood count were developed on day 7 after onset of fever with the x‐ray finding of bilateral multifocal patchy infiltration. COVID‐19 infection has been confirmed by reverse real‐time polymerase chain reaction (PCR) in nasal swab as well as found in stool. Darunavir together with ritonavir, hydroxychloroquine, azithromycin, and favipiravir was initiated on the first day of admission at primary hospital. Patient has been transferred to our hospital on day 2 of admission in which tacrolimus together with MMF was discontinued. High‐flow nasal cannula oxygen therapy was required on days 4‐5 of hospitalization. Tocilizumab was administered after rising of serum IL‐6 level. Symptoms of pneumonia were improved in which no oxygen treatment required from day 10 of hospitalization. Drug interaction between tacrolimus and anti‐viral treatment leads to severely high level of tacrolimus which caused reversible acute kidney injury (AKI) after supportive treatment. [ABSTRACT FROM AUTHOR]

A rapidly emerging and highly concentrated hepatitis C virus (HCV) outbreak has recently been observed among both acute and chronic HIV‐positive men who have sex with men (MSM) in Bangkok, Thailand. NS5B regions of the HCV genome were amplified using nested PCR and sequenced. Phylogenetic inference was constructed by Maximum Likelihood methods and clusters were identified with support and genetic distance thresholds of 85% and of 4.5%. Forty‐eight (25 acute HIV and 23 chronic HIV) MSM with incident HCV infection were included in the analysis. HCV genotype (GT) was 85% GT 1a and 15% GT 3a or 3b. Median age at HCV diagnosis was 34 (interquartile range, 28‐41) years. 83.3% (40/48) had history of syphilis infection and 36% (16/44) reported crystal methamphetamine use. Only 2 (4%) reported ever injecting drugs, both crystal methamphetamine. In the phylogenetic clustering analysis, 83% belonged to one of two clusters: one large (75%) and one small (8%) cluster. All clusters were GT 1a. MSM with acute HIV infection were more likely to be in a cluster (92%) than those with chronic infection (74%). HCV screening should be regularly performed for MSM in ART clinics, and offering direct‐acting antiviral agents to all MSM with HCV infection might contain the HCV epidemic from expanding further. [ABSTRACT FROM AUTHOR]

Objectives: Early mortality among those still initiating antiretroviral therapy (ART) with advanced stages of HIV infection in resource‐limited settings remains high despite recommendations for universal HIV treatment. We investigated risk factors associated with early mortality in people living with HIV (PLHIV) starting ART at low CD4 levels in the Asia‐Pacific. Methods: PLHIV enrolled in the Therapeutics, Research, Education and AIDS Training in Asia (TREAT Asia) HIV Observational Database (TAHOD) who initiated ART with a CD4 count < 100 cells/μL between 2003 and 2018 were included in the study. Early mortality was defined as death within 1 year of ART initiation. PLHIV in follow‐up for > 1 year were censored at 12 months. Competing risk regression was used to analyse risk factors with loss to follow‐up as a competing risk. Results: A total of 1813 PLHIV were included in the study, of whom 74% were male. With 73 (4%) deaths, the overall first‐year mortality rate was 4.27 per 100 person‐years (PY). Thirty‐eight deaths (52%) were AIDS‐related, 10 (14%) were immune reconstituted inflammatory syndrome (IRIS)‐related, 13 (18%) were non‐AIDS‐related and 12 (16%) had an unknown cause. Risk factors included having a body mass index (BMI) < 18.5 [sub‐hazard ratio (SHR) 2.91; 95% confidence interval (CI) 1.60–5.32] compared to BMI 18.5–24.9, and alanine aminotransferase (ALT) ≥ 5 times its upper limit of normal (ULN) (SHR 6.14; 95% CI 1.62–23.20) compared to ALT < 5 times its ULN. A higher CD4 count (51–100 cells/μL: SHR 0.28; 95% CI 0.14–0.55; and > 100 cells/μL: SHR 0.12; 95% CI 0.05–0.26) was associated with reduced hazard for mortality compared to CD4 count ≤ 25 cells/μL. Conclusions: Fifty‐two per cent of early deaths were AIDS‐related. Efforts to initiate ART at CD4 counts > 50 cell/μL are associated with improved short‐term survival rates, even in those with late stages of HIV disease. [ABSTRACT FROM AUTHOR]

Introduction: People living with HIV (PLHIV) have an elevated risk of atherosclerotic cardiovascular disease (CVD) compared to their HIV‐negative peers. Expanding statin use may help alleviate this burden. However, the choice of statin in the context of antiretroviral therapy is challenging. Pravastatin and pitavastatin improve cholesterol levels in PLHIV without interacting substantially with antiretroviral therapy. They are also more expensive than most statins. We evaluated the cost‐effectiveness of pravastatin and pitavastatin for the primary prevention of CVD among PLHIV in Thailand who are not currently using lipid‐lowering therapy. Methods: We developed a discrete‐state microsimulation model that randomly selected (with replacement) individuals from the TREAT Asia HIV Observational Database cohort who were aged 40 to 75 years, receiving antiretroviral therapy in Thailand, and not using lipid‐lowering therapy. The model simulated each individual's probability of experiencing CVD. We evaluated: (1) treating no one with statins; (2) treating everyone with pravastatin 20mg/day (drug cost 7568 Thai Baht ($US243)/year) and (3) treating everyone with pitavastatin 2 mg/day (drug cost 8182 Baht ($US263)/year). Direct medical costs and quality‐adjusted life‐years (QALYs) were assigned in annual cycles over a 20‐year time horizon and discounted at 3% per year. We assumed the Thai healthcare sector perspective. Results: Pravastatin was estimated to be less effective and less cost‐effective than pitavastatin and was therefore dominated (extended) by pitavastatin. Patients receiving pitavastatin accumulated 0.042 additional QALYs compared with those not using a statin, at an extra cost of 96,442 Baht ($US3095), giving an incremental cost‐effectiveness ratio of 2,300,000 Baht ($US73,812)/QALY gained. These findings were sensitive to statin costs and statin efficacy, pill burden, and targeting of PLHIV based on CVD risk. At a willingness‐to‐pay threshold of 160,000 Baht ($US5135)/QALY gained, we estimated that pravastatin would become cost‐effective at an annual cost of 415 Baht ($US13.30)/year and pitavastatin would become cost‐effective at an annual cost of 600 Baht ($US19.30)/year. Conclusions: Neither pravastatin nor pitavastatin were projected to be cost‐effective for the primary prevention of CVD among PLHIV in Thailand who are not currently using lipid‐lowering therapy. We do not recommend expanding current use of these drugs among PLHIV in Thailand without substantial price reduction. [ABSTRACT FROM AUTHOR]

Objectives: Initial antiretroviral therapy (ART) causes loss of bone mineral density (BMD) over the first 1–2 years. Whether this loss continues with longer therapy is unclear. We determined changes in bone and spine BMD over 5 years in adults receiving immediate or deferred initial ART. Methods: In the Strategic Timing of Antiretroviral Therapy (START) BMD substudy, ART‐naïve adults with CD4 counts > 500 cells/μL were randomized to immediate or deferred ART. Deferred group participants not yet on ART were offered ART after May 2015. Mean per cent changes in total hip and lumbar spine BMD (measured annually by dual‐energy X‐ray absorptiometry) were compared between groups using longitudinal mixed models. Fracture rates were also compared between groups for all START participants. Results: Substudy participants (immediate group, n = 201; deferred group, n = 210; median age 32 years; 80% non‐white; 24% female) were followed for a mean 4.5 years until December 2016. In the immediate group, > 96% used ART throughout. In the deferred group, 16%, 58% and 94% used ART at years 1, 3 and 5, respectively. BMD decreased more in the immediate group initially; groups had converged by year 3 at the spine and year 4 at the hip by intent‐to‐treat (ITT). BMD changes after year 1 were similar in the immediate group and in those off ART in the deferred group [mean difference: spine, 0.03% per year; 95% confidence interval (CI) −0.4, 0.4; P = 0.88; hip, −0.2% per year; 95% CI −0.7, 0.3; P = 0.37]. Fracture incidence did not differ significantly between groups (immediate group, 0.86/100 person‐years versus deferred group, 0.85/100 person‐years; hazard ratio 1.01; 95% CI 0.76, 1.35; P = 0.98). Conclusions: Significant ART‐induced bone loss slowed after the first year of ART and became similar to that in untreated HIV infection. [ABSTRACT FROM AUTHOR]

Objectives: With earlier antiretroviral therapy (ART) initiation, time spent in HIV care is expected to increase. We aimed to investigate loss to follow‐up (LTFU) in Asian patients who remained in care 5 years after ART initiation. Methods: Long‐term LTFU was defined as LTFU occurring after 5 years on ART. LTFU was defined as (1) patients not seen in the previous 12 months; and (2) patients not seen in the previous 6 months. Factors associated with LTFU were analysed using competing risk regression. Results: Under the 12‐month definition, the LTFU rate was 2.0 per 100 person‐years (PY) [95% confidence interval (CI) 1.8–2.2 among 4889 patients included in the study. LTFU was associated with age > 50 years [sub‐hazard ratio (SHR) 1.64; 95% CI 1.17–2.31] compared with 31–40 years, viral load ≥ 1000 copies/mL (SHR 1.86; 95% CI 1.16–2.97) compared with viral load < 1000 copies/mL, and hepatitis C coinfection (SHR 1.48; 95% CI 1.06–2.05). LTFU was less likely to occur in females, in individuals with higher CD4 counts, in those with self‐reported adherence ≥ 95%, and in those living in high‐income countries. The 6‐month LTFU definition produced an incidence rate of 3.2 per 100 PY (95% CI 2.9–3.4 and had similar associations but with greater risks of LTFU for ART initiation in later years (2006–2009: SHR 2.38; 95% CI 1.93–2.94; and 2010–2011: SHR 4.26; 95% CI 3.17–5.73) compared with 2003–2005. Conclusions: The long‐term LTFU rate in our cohort was low, with older age being associated with LTFU. The increased risk of LTFU with later years of ART initiation in the 6‐month analysis, but not the 12‐month analysis, implies that there was a possible move towards longer HIV clinic scheduling in Asia. [ABSTRACT FROM AUTHOR]

Objectives: With aging of the HIV‐positive population, cardiovascular disease (CVD) increasingly contributes to morbidity and mortality. We investigated CVD‐related and other causes of death (CODs) and factors associated with CVD in a multi‐country Asian HIV‐positive cohort. Methods: Patient data from 2003–2017 were obtained from the Therapeutics, Research, Education and AIDS Training in Asia (TREAT Asia) HIV Observational Database (TAHOD). We included patients on antiretroviral therapy (ART) with > 1 day of follow‐up. Cumulative incidences were plotted for CVD‐related, AIDS‐related, non‐AIDS‐related, and unknown CODs, and any CVD (i.e. fatal and nonfatal). Competing risk regression was used to assess risk factors of any CVD. Results: Of 8069 patients with a median follow‐up of 7.3 years [interquartile range (IQR) 4.4–10.7 years], 378 patients died [incidence rate (IR) 6.2 per 1000 person‐years (PY)], and this total included 22 CVD‐related deaths (IR 0.36 per 1000 PY). Factors significantly associated with any CVD event (IR 2.2 per 1000 PY) were older age [sub‐hazard ratio (sHR) 2.21; 95% confidence interval (CI) 1.36–3.58 for age 41–50 years; sHR 5.52; 95% CI 3.43–8.91 for ≥ 51 years, compared with < 40 years], high blood pressure (sHR 1.62; 95% CI 1.04–2.52), high total cholesterol (sHR 1.89; 95% CI 1.27–2.82), high triglycerides (sHR 1.55; 95% CI 1.02–2.37) and high body mass index (BMI) (sHR 1.66; 95% CI 1.12–2.46). CVD crude IRs were lower in the later ART initiation period and in lower middle‐ and upper middle‐income countries. Conclusions: The development of fatal and nonfatal CVD events in our cohort was associated with older age, and treatable risk factors such as high blood pressure, triglycerides, total cholesterol and BMI. Lower CVD event rates in middle‐income countries may indicate under‐diagnosis of CVD in Asian‐Pacific resource‐limited settings. [ABSTRACT FROM AUTHOR]

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Aim: Donor-specific antibody (DSA) is a widely-used biomarker for antibody-mediated rejection (ABMR) but correctly indicates only 30–40% of patients with ABMR. Additional biomarkers of ABMR in kidney transplant recipients are needed. Methods: All 68 kidney transplanted-recipients enrolled in this study were negative for graft rejection as determined by surveillance-biopsy ELISA at day 7 post-transplantation. Allograft biopsy was then performed at 6 months post-transplantation for subclinical-ABMR detection. Recipients were stratified by pre-transplant DSA and BAFF at day 7 into four groups. Results: During the study period, 13.2% of the recipients demonstrated subclinical-ABMR at 6 months, without patient with clinical ABMR presentations. Overall mean BAFF at day 7 was 393 pg/mL (95% CI = 316–471 pg/mL). The optimal cut-off value for low vs. high BAFF level was 573 pg/mL, with sensitivity and specificity at 77.8% and 88.1%, respectively. Fifty percent of recipients with high BAFF at day 7 (14 patients) and only 3.7% of patients with low BAFF demonstrated ABMR (P < 0.05). Indeed, ABMR was more common in patients high BAFF level (hazard ratio = 7.30; 95% CI = 3.77–14.15). The prevalence of ABMR among negative pre-transplant DSA/low BAFF, positive DSA/low BAFF, negative DSA/high BAFF, and positive DSA/ high BAFF recipients were 4.4, 0, 37.5 and 66.7%, respectively (P < 0.05). Conclusions: Post-transplant ABMR can be predicted by perioperative serum BAFF level. Together with DSA testing, BAFF provides additional predictive value for ABMR. [ABSTRACT FROM AUTHOR]

Introduction: Although substitutions of antiretroviral regimen are generally safe, most data on substitutions are based on results from clinical trials. The objective of this study was to evaluate the treatment outcomes of substituting antiretroviral regimen in virologically suppressed HIV-infected patients in non-clinical trial settings in Asian countries. Methods: The study population consisted of HIV-infected patients enrolled in the TREAT Asia HIV Observational Database (TAHOD). Individuals were included in this analysis if they started combination antiretroviral treatment (cART) after 2002, were being treated at a centre that documented a median rate of viral load monitoring =0.8 tests/patient/year among TAHOD enrolees, and experienced a minor or major treatment substitution while on virally suppressive cART. The primary endpoint to evaluate outcomes was clinical or virological failure (VF), followed by an ART class change. Clinical failure was defined as death or an AIDS diagnosis. VF was defined as confirmed viral load measurements =400 copies/mL followed by an ART class change within six months. Minor regimen substitutions were defined as within-class changes and major regimen substitutions were defined as changes to a drug class. The patterns of substitutions and rate of clinical or VF after substitutions were analyzed. Results: Of 3994 adults who started ART after 2002, 3119 (78.1%) had at least one period of virological suppression. Among these, 1170 (37.5%) underwent a minor regimen substitution, and 296 (9.5%) underwent a major regimen substitution during suppression. The rates of clinical or VF were 1.48/100 person years (95% CI 1.14 to 1.91) in the minor substitution group, 2.85/100 person years (95% CI 1.88 to 4.33) in the major substitution group and 2.53/100 person years (95% CI 2.20 to 2.92) among patients that did not undergo a treatment substitution. Conclusions: The rate of clinical or VF was low in both major and minor substitution groups, showing that regimen substitution is generally effective in non-clinical trial settings in Asian countries. [ABSTRACT FROM AUTHOR]

Data on markers of hepatitis C virus ( HCV) disease in HIV- HCV-coinfected patients in resource-limited settings are scarce. We assessed HCV RNA, HCV genotype ( GT), IL28B GT and liver fibrosis (FibroScan®) in 480 HIV-infected patients with positive HCV antibody in four HIV treatment centres in South-East Asia. We enrolled 165 (34.4%) patients in Jakarta, 158 (32.9%) in Bangkok, 110 (22.9%) in Hanoi and 47 (9.8%) in Kuala Lumpur. Overall, 426 (88.8%) were male, the median ( IQR) age was 38.1 (34.7-42.5) years, 365 (76.0%) reported HCV exposure through injecting drug use, and 453 (94.4%) were on combination antiretroviral therapy. The median ( IQR) CD4 count was 446 (325-614) cells/mm3 and 208 (94.1%) of 221 patients tested had HIV-1 RNA <400 copies/mL. A total of 412 (85.8%) had detectable HCV RNA, at a median ( IQR) of 6.2 (5.4-6.6) log10 IU/ mL. Among 380 patients with HCV GT, 223 (58.7%) had GT1, 97 (25.5%) had GT3, 43 (11.3%) had GT6, eight (2.1%) had GT4, two (0.5%) had GT2, and seven (1.8%) had indeterminate GT. Of 222 patients with IL28B testing, 189 (85.1%) had rs12979860 CC genotype, and 199 (89.6%) had rs8099917 TT genotype. Of 380 patients with FibroScan®, 143 (37.6%) had no/mild liver fibrosis (F0-F1), 83 (21.8%) had moderate fibrosis (F2), 74 (19.5%) had severe fibrosis (F3), and 79 (20.8%) had cirrhosis (F4). One patient (0.3%) had FibroScan® failure. In conclusion, a high proportion of HIV- HCV-coinfected patients had chronic HCV infection. HCV GT1 was predominant, and 62% of patients had liver disease warranting prompt treatment (≥F2). [ABSTRACT FROM AUTHOR]

Aim Recurrent IgA nephropathy (IgAN) is a common recurrent glomerular disease after kidney transplantation. Recurrent IgAN, in particular, with crescent formation or endocapillary proliferation might result in kidney allograft loss. However, the current treatment options of recurrent IgAN are conflicting. Methods We have reported three kidney-transplanted recipients with biopsy-proven recurrent IgAN treated with four consecutive months of rituximab at the dose of 375 mg/1.73m2 without corticosteroids. Results At median follow-up 20 months following rituximab administration, all three recipients demonstrated decrease in proteinuria severity, slow disease progression with a well-tolerated condition. This therapeutic effect is most probably mediated by the B cell depletion. Conclusion Our three case reports suggest that the disease severity of recurrent IgAN with endocapillary proliferation regardless of crescent formation can be minimized by the four doses of monthly rituximab regimen. [ABSTRACT FROM AUTHOR]

The preservation of kidney function after kidney donation depends on the kidney reserve - the potential of the remaining kidney to boost their function after loss of the other kidney. In Traditional Chinese Medicine, size and shape of the external ears are examined to evaluate the person's kidney health. We hypothesized that ear size might be a practical yet overlooked marker of kidney reserve. Fifty kidney transplantation donors were participated in this study. The length and width of both ears of all participants were measured during one of the post-donation visits. Pre-donation serum creatinine and post-donation serum creatinine as well as other relevant parameters (age, sex, weight, height, etc.) of the participants were extracted from medical records. The estimated GFR was calculated from serum creatinine, age and sex using the CKD-EPI equation. Ear length negatively associated with %GFR decline after kidney donation. For every 1 cm increase in ear length, it was associated with 5.7% less GFR decline after kidney donation (95% Confidence Interval 0.2 to 11.3, P = 0.04). Ear width, as well as age, sex, body weight, height, body mass index, and pre-donation eGFR did not significantly associate with the GFR decline. Our findings support the notion of Traditional Chinese Medicine that ear morphology may be associated with kidney health and suggest that ear length might be a useful predictor of kidney function decline after kidney donation. [ABSTRACT FROM AUTHOR]

Objectives HIV infection is associated with a higher prevalence of low bone mineral density ( BMD) and fractures than that found in the general population. There are limited data in HIV-positive adults, naïve to antiretroviral therapy ( ART), with which to estimate the relative contribution of untreated HIV infection to bone loss. Methods The primary objective of the Strategic Timing of AntiRetroviral Treatment ( START) Bone Mineral Density Substudy is to compare the effect of immediate versus deferred initial ART on bone. We evaluated traditional, demographic, HIV-related and immunological factors for their associations with baseline hip and lumbar spine BMD, measured by dual-energy X-ray absorptiometry, using multiple regression. Results A total of 424 ART-naïve participants were enrolled at 33 sites on six continents; the mean age was 34 years [standard deviation ( SD) 10.1 years], 79.0% were nonwhite, 26.0% were women, and 12.5% had a body mass index ( BMI) < 20 kg/m2. Mean ( SD) Z-scores were −0.41 (0.94) at the spine and −0.36 (0.88) for total hip; 1.9% had osteoporosis and 35.1% had low BMD (hip or spine T-score < −1.0). Factors independently associated with lower BMD at the hip and spine were female sex, Latino/Hispanic ethnicity, lower BMI and higher estimated glomerular filtration rate. Longer time since HIV diagnosis was associated with lower hip BMD. Current or nadir CD4 cell count and HIV viral load were not associated with BMD. Conclusions In this geographically and racially diverse population of ART-naïve adults with normal CD4 cell counts, low BMD was common, but osteoporosis was rare. Lower BMD was significantly associated with traditional risk factors but not with CD4 cell count or viral load. [ABSTRACT FROM AUTHOR]

Aim To report the kidney transplant activity and survival data during the past 25 years from the Thai Transplant Registry. Methods By using the registry database that was collected and updated yearly by 26 transplant centres across the country, we have reported the donor, recipient, and transplant characteristics during the past 25 years from 1987 to 2012. The primary outcome was graft loss that was defined as return to dialysis, graft removal, retransplant, or patient death. Results 465 kidney transplants were performed in 2012, an 8.1% and 23.0% increase in living and deceased donor transplants compared to the previous year, respectively. Between 1987 and 2012 with the data of 3808 recipients, patient survival and graft survival improved significantly. Traffic accident was the most common cause of death in brain-dead donors. Additionally, the most common cause of end-stage kidney disease was glomerulonephritis. Infection has been among the most common causes of death in kidney transplant recipients. Conclusion We have reported the total number, the graft and the patient survival data of kidney transplant recipients in Thailand for the period from 1987 to 2012. Although the number of patients is much lower than that in the developed countries, the patients and the graft survival rates are comparable. [ABSTRACT FROM AUTHOR]

Background and Aim: Vitamin D insufficiency plays an important role in liver fibrosis in hepatitis C virus (HCV)-infected patients. We assessed liver fibrosis by transient elastography and 25 hydroxy vitamin D [25(OH)D] status in HCV-infected patients, with (HIV/HCV) or without HIV co-infection (HCV) from Thailand. Methods: Fibrosis stage was defined as mild (< 7.1 kPa); moderate (7.2-9.4 kPa); severe (9.5-14 kPa), and cirrhosis (> 14 kPa). Hypovitaminosis D was defined as 25(OH)D < 30 ng/mL. Logistic regression analyses were used to assess predictors for significant fibrosis. Serum 25(OH) D levels, HCV genotypes (GT), interleukin-28B (IL28B) and HCV-RNA were assessed. Results: A total of 331 HCV and 130 HIV/HCV patients were enrolled (70% male, 35% people who inject drugs [PWIDs]). HCV GT distribution was as follows: GT3 47%, GT1 34%, GT6 17%. IL-28B CC genotype (rs12979860) were found in 88% of HIV/HCV and 85% of HCV. In HCV, liver fibrosis was mild in 56.5%; moderate in 18.4%; severe in 12.4%; and cirrhosis in 12.7%. In HIV/HCV, these figures were 30.6%, 27.8%, 17.6%, and 24.1%, respectively. Patients with significant fibrosis were more often male, older, with HIV infection, hypovitaminosis D, and less likely to be infected with GT6. Factors associated with significant fibrosis by multivariate analysis were HIV infection (adjusted odd ratio [95% confidential interval]: 2.67, 1.20-5.93), P = 0.016, Fib-4 score > 1.45 (6.30, 2.70-14.74), P < 0.001, and hypovitaminosis D (2.48, 1.09-5.67), P = 0.031. GT 6 was less likely to have advanced liver fibrosis (0.17, 0.05-0.65), P = 0.01. Conclusions: HIV infection, Fib-4 score > 1.45, and hypovitaminosis D are strong and independent predictors for the presence of advanced fibrosis in our HCV-infected patients. These data highlight the urgent need of HCV treatment and vitamin D supplement in resource-limited settings. [ABSTRACT FROM AUTHOR]

Lupus nephritis ( LN) is a common and important manifestation of systemic lupus erythematosus ( SLE). Evidence suggests higher rates of lupus renal involvement in Asian populations, and maybe more severe nephritis, compared with other racial or ethnic groups. The management of LN has evolved considerably over the past three decades, based on observations from clinical studies that investigated different immunosuppressive agents including corticosteroids, cyclophosphamide, azathioprine, mycophenolic acid, calcineurin inhibitors and novel biologic therapies. This is accompanied by improvements in both the short-term treatment response rate and long-term renal function preservation. Treatment guidelines for LN have recently been issued by rheumatology and nephrology communities in U.S.A. and Europe. In view of the racial difference in disease manifestation and response to therapy, and the substantial disease burden in Asia, a panel of 15 nephrologists and rheumatologists from different Asian regions with extensive experience in lupus nephritis - the Steering Group for the Asian Lupus Nephritis Network ( ALNN) - met and discussed the management of lupus nephritis in Asian patients. The group has also reviewed and deliberated on the recently published recommendations from other parts of the world. This manuscript summarizes the discussions by the group and presents consensus views on the clinical management and treatment of adult Asian patients with LN, taking into account both the available evidence and expert opinion in areas where evidence remains to be sought. [ABSTRACT FROM AUTHOR]

Lupus nephritis (LN) is a common and important manifestation of systemic lupus erythematosus (SLE). Evidence suggests higher rates of lupus renal involvement in Asian populations, and maybe more severe nephritis, compared with other racial or ethnic groups. The management of LN has evolved considerably over the past three decades, based on observations from clinical studies that investigated different immunosuppressive agents including corticosteroids, cyclophosphamide, azathioprine, mycophenolic acid, calcineurin inhibitors and novel biologic therapies. This is accompanied by improvements in both the short-term treatment response rate and long-term renal function preservation. Treatment guidelines for LN have recently been issued by rheumatology and nephrology communities in U.S.A. and Europe. In view of the racial difference in disease manifestation and response to therapy, and the substantial disease burden in Asia, a panel of 15 nephrologists and rheumatologists from different Asian regions with extensive experience in lupus nephritis- the Steering Group for the Asian Lupus Nephritis Network (ALNN) - met and discussed the management of lupus nephritis in Asian patients. The group has also reviewed and deliberated on the recently published recommendations from other parts of the world. This manuscript summarizes the discussions by the group and presents consensus views on the clinical management and treatment of adult Asian patients with LN, taking into account both the available evidence and expert opinion in areas where evidence remains to be sought. [ABSTRACT FROM AUTHOR]

Cytomegalovirus tubulo-glomerulitis and intratubular granuloma: Key histopathological findings in allograft cytomegalovirus infection Positive CMV immunohistochemical staining in the affected glomerulus (D) gl We investigated the cause of non-resolving CMV infection and found that ganciclovir vials were inappropriately stored at her house and had direct exposure to sunlight, which might affect the drug stability. Cytomegalovirus (CMV) IgG were both positive for recipient and donor. [Extracted from the article]

Delayed initiation of renal replacement therapy ( RRT) in critically ill acute kidney injury ( AKI) patients results in high mortality while too early RRT causes unnecessary risks of the treatment. Current traditional indications cannot clearly identify the appropriate time for initiating RRT. This prospective cohort study was conducted to determine the accuracy of using plasma neutrophil gelatinase-associated lipocalin ( pNGAL) and urine NGAL ( uNGAL) in early identifying of the AKI patients who subsequently required RRT. Forty-seven critically ill patients with AKI stage 2-3 who did not reach the traditional indications for RRT were enrolled in this study. The pNGAL, uNGAL, and other parameters were determined in each patient. The primary end point was RRT initiation according to the traditional indications within 3 days. The mean age of the patients was 63.0 ± 18.1 years. pNGAL could predict subsequent RRT requirements with area under ROC 0.813 ( P < 0.001, 95% CI 0.66-0.90). The cut-off point of 960 ng/ mL provided sensitivity and specificity of 72.2 and 89.6%, respectively, and positive and negative predictive values of 81.25% and 83.8%, respectively. The uNGAL provided slightly lower significance of statistical parameters. The combination of pNGAL level of 960 ng/ mL and APACHE II score of 20 improved statistical values. In conclusion, pNGAL is an excellent early biomarker for RRT initiation in critically ill patients with AKI stage 2-3. The pNGAL value of 960 ng/ mL, alone or in combination with APACHE II score might be used as the early new indicator for early initiation of RRT in AKI stage 2-3 and this might improve patient survival. [ABSTRACT FROM AUTHOR]

As universal coverage for pediatric kidney transplantation ( KT) was introduced in Thailand in 2008, the number of recipients has been increasing. We evaluated predictive factors for graft failure to understand how to improve clinical outcomes in these children. Using data obtained from the National Transplant registry, we assessed the risk of graft failure using the Kaplan- Meier method and Cox proportional hazards regression. Altogether, 201 recipients aged <21 yr at the time of KT were studied. Living donors ( LD) were significantly older than deceased donor ( DD). Mean cold ischemia time of DD was 17 h. The mean donor glomerular filtration rate ( GFR) was 84.0 mL/min/1.73 m2. Induction immunosuppressive therapy was administered more frequently in DD than in LDKT. Delayed graft function ( DGF) occurred in 36 transplants. Over 719 person years of follow-up, 42 graft failures occurred. Graft survival at one, three, and five yr post-transplant were 95%, 88% and 76%, respectively. Two factors independently predicted graft failure in multivariate analysis. The hazard ratios for graft failure in patients with DGF and in patients with donor GFR of ≤30 mL/min/1.73 m2 were 2.5 and 9.7, respectively. Pediatric recipients should receive the first priority for allografts from young DD with a good GFR, and DGF should be meticulously prevented. [ABSTRACT FROM AUTHOR]

Co-infection of HBV with HIV results in an accelerated course of HBV-associated chronic liver disease. Several studies have shown that viral mutations are related to disease progression in mono-infection with HBV. However, it is unclear whether HBV mutation patterns might differ between co-infected and mono-infected patients. To compare the frequencies and mutation patterns in the HBV genome between co-infection and mono-infection. Twenty-four treatment-naïve co-infected and 31 treatment-naïve mono-infected Thai patients were included. HBV mutations were characterized by whole genome sequencing of virus serum samples. The clinical features and frequency of known clinically significant mutations were compared between the two groups. No significant difference between the groups was found with respect to sex, age and HBeAg. However, HBV DNA levels were significantly higher in co-infected patients. The distribution of HBV genotypes was comparable between the two groups and restricted mostly to sub-genotypes C1 and B2. An isolate with recombinants of genotypes G/C1 was also identified in a patient with co-infection. There was no difference in the prevalence of mutations in the enhancer II/basal core promoter/precore region, pre-S/S and polymerase genes between the two groups. In conclusion, dual infections tend to engender increased HBV DNA levels. There was no major difference in the frequencies of common HBV mutations between co-infected and mono-infected patients. Thus, HBV mutations may not contribute to disease pathogenesis in Thai patients with co-infection. J. Med. Virol. 85:16-25, 2012. © 2012 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

Objective There is growing concern regarding cardiovascular disease in HIV-infected individuals in developing countries such as Thailand. We evaluated the 10-year risk of coronary heart disease (CHD) in a Thai HIV-infected cohort using three cardiovascular risk equations, and assessed the level of agreement among their predictions. Methods We carried out a cross-sectional analysis of data on 785 Thai subjects followed prospectively in the HIV Netherlands Australia Thailand Collaboration (HIV-NAT) cohort study from 1996 to 2009. Cardiovascular risk factor history, along with relevant laboratory and clinical data, was collected at follow-up clinic visits. Ten-year risks of CHD were calculated using the Framingham, Ramathibodi-Electricity Generating Authority of Thailand (Rama-EGAT) and Data Collection on Adverse Effects of Anti-HIV Drugs (D:A:D) risk equations. Results The mean age of the patients was 41.0 years; 55% of the subjects were male. The mean duration of antiretroviral therapy was 7.7 years. The prevalence of cardiovascular risk factors was low, with the most common risk factor being low high-density lipoprotein (HDL) (36.3%). The prevalence of high cardiovascular risk scores (defined as 10-year risk of CHD≥10%) was also low: 9.9, 2.1 and 0.8%, by the Framingham, Rama-EGAT and D:A:D scoring systems, respectively. Only eight subjects (1.0%) had a history of CHD. Bland-Altman plots showed that the Framingham equation predicted a higher risk of CVD compared with the Rama-EGAT and D:A:D equations, which agreed relatively well. Conclusion The predicted cardiovascular risk in this HIV-infected Thai cohort was relatively low. The agreement among the Rama-EGAT and D:A:D risk scores suggests that both equations may be appropriate estimators of cardiovascular risk in this population. [ABSTRACT FROM AUTHOR]

There were no statistically significant difference in allele and genotype frequency of the polymorphisms within the vascular endothelial growth factor ( VEGF) gene (−460 and +405) between 193 systemic lupus erythematosus patients and 234 healthy controls. However, the +405 GG was significantly associated with lupus nephritis (LN) patients with low VEGF mRNA expression and LN with end-stage renal disease. [ABSTRACT FROM AUTHOR]

Several dose-finding studies of boosted protease inhibitors have demonstrated that doses lower than those recommended in Caucasian populations exhibit in the Thai population similar pharmacokinetic (PK) properties with sustained virological suppression but reduced toxicity. We therefore evaluated the PK profiles of lower than the standard doses of atazanavir/ritonavir (ATV/RTV) in 22 adult Thai patients with well-suppressed human immunodeficiency virus 1 (HIV-1) infection. The PK parameters of ATV/RTV at a dosage of 200/100 mg once daily, plus two nucleoside reverse transcriptase inhibitors, were significantly lower than those associated with a dosage of 300/100 mg once daily in the same patients. In addition, the PK parameters for the lower dosage in these Thai patients were comparable to historical data from Caucasian cohorts who received the standard dose of ATV/RTV (300/100 mg). None of the patients showed subtherapeutic values of <0.15 mg/l at any time point. Bilirubin concentration decreased significantly after dose reduction, and viral load remained at <50 copies/ml in all subjects. Therefore, ATV/RTV at a dose of 200/100 mg once daily (plus appropriate backbone medication) warrants further long-term efficacy studies, particularly in patients of Thai and other Asian ethnicities.Clinical Pharmacology & Therapeutics (2009); 85, 4, 402–408 doi:10.1038/clpt.2008.244 [ABSTRACT FROM AUTHOR]

In this study, the association between the systemic lupus erythematosus (SLE) susceptibility and the new candidate genes, IFNA1, IFNA2 and IFNA5 genes, major interferon-alpha subtypes, in responses to viral infection was investigated. Allele and genotype frequencies of each marker were compared between 150 SLE patients and 150 healthy control subjects. This study indicated that the A/A genotype of IFNA5 (−2529) and the G/G genotype of IFNA1 (−1823) were associated with the protection of SLE disease in a recessive model [ Pc = 0.03, P = 0.01, odds ratio (OR) = 0.4, 95% confidence interval (CI) = 0.2–0.8 and Pc = 0.09, P = 0.03, OR = 0.5, 95% CI = 0.2–0.9, respectively). Multifactor dimensionality reduction analysis showed a marginal interaction between IFNA5 (−2529) and IFNA1 (−1823) gene, with a cross-validation consistency of 10 of 10 and a prediction error of 46% (permutation P-value = 0.05). This is the first report of positive association of IFNA gene in SLE, especially the role of specific subtypes IFNA1 and IFNA5. [ABSTRACT FROM AUTHOR]

Polymorphism of vascular endothelial growth factor (VEGF) influences the VEGF production and is subjected to genetic susceptibility of many diseases including psoriasis. Three single nucleotide polymorphisms (SNPs) within the promoter and exon 1 region [−2578(C/A), −460(C/T) and +405(C/G)] were analyzed in 154 patients with chronic plaque psoriasis and in 234 ethnically matched healthy controls from Thailand. The CTG (−2578/−460/+405) haplotype frequency was higher in patients with early-onset psoriasis (44.12%) compared with healthy controls (33.33%) (odds ratio = 1.54, 95% confidence interval = 1.08–2.18, P = 0.016, corrected P value: Pc = 0.048). The results suggest that the CTG haplotype can be used as a genetic marker for psoriasis especially the early-onset group of Thais. [ABSTRACT FROM AUTHOR]

The production of cytokine varies among individuals and correlates with the polymorphism of cytokine genes. Three functional single nucleotide polymorphisms (SNPs) at position –863, –308, and –238 in the tumour necrosis factor alpha (TNF-α) gene promoter were analysed for association with systemic lupus erythematosus (SLE) ( n = 154), and clinical manifestations in a Thai population were compared with 154 ethnically matched controls. The genotyping was determined by polymerase chain reaction-restriction fragment length polymorphism method. The association between these SNPs and SLE was analysed using chi-squared test. The –863A allele and –863A, –308G, –238G haplotype were found to be significantly increased in SLE patients (25%) compared with healthy controls (15.3%) (Pc = 0.009, OR = 1.85, 95% CI = 1.21–2.83). In addition –863A allele was found to be significantly increased in the SLE group with Raynaud's phenomenon compared to SLE without Raynaud's phenomenon (35% vs. 19.4%) (Pc = 0.048, OR = 2.23, 95% CI = 1.21–4.10). The –863A allele of TNF-α gene and the extended haplotype of –863A, –308G, –238G can be used as a genetic marker for SLE susceptibility in Thai populations. In addition, the –863A genotype could produce high TNF levels and potentially induce the occurrence of Raynaud's phenomenon. [ABSTRACT FROM AUTHOR]

Several linkage analyses have consistently shown that systemic lupus erythematosus (SLE) susceptible genes are located on chromosome 1q21-44. In this study, two major candidate genes, interleukin-10 (IL-10) and Fc gamma receptor IIa (FcγRIIa), within these regions were investigated in Thai SLE patients. The genotyping of three single-nucleotide polymorphisms (promoter area: −1082, −819 and −592) within IL-10 gene and one polymorphism (change amino acid at position 131) within FcγRIIa gene was determined in 195 SLE patients and 159 ethnically matched controls. The RR/RH genotypes of FcγRIIa were found to be significantly increased in SLE patients compared with healthy controls [OR = 2.01, 95% confidence interval (CI) = 1.28–3.14, P= 0.001]. Interestingly, the synergistic effect between RR/RH genotypes of FcγRIIa and ACC/ACC haplotype of IL-10 in susceptibility to SLE was observed (OR = 7.84, 95% CI = 1.60–52.04, P= 0.002). In addition, the FcγRIIa, RR homozygotes was also strongly associated with anticardiolipin antibody production (OR = 6.09, 95% CI = 1.38–30.54, P= 0.006). The result demonstrated that ACC haplotype of IL-10 gene and FcγRIIa R131 polymorphism can be used as marker for genetic susceptibility and severity to SLE in Thai population, particularly individuals carrying both specific genotypes. [ABSTRACT FROM AUTHOR]

Praditpornsilpa K, Avihingsanon Y, Nivatvong S, Kansanabuch T, Eiam-Ong S, Tiranathanagul K, Chusil S, Tungsanga K. Outcome of microemulsion cyclosporine C2 concentration monitoring in kidney transplantation.Clin Transplant 2005 DOI: 10.1111/j.1399-0012.2005.000343.x© Blackwell Munksgaard, 2005Profiling of absorption of cyclosporine (CsA) microemulsion is a concept in therapeutic drug monitoring (TDM) designed to optimize the clinical benefits of the drug in transplant recipients. A single blood concentration at 2 h (C2) after CsA microemulsion administration in kidney transplant recipients accurately predicts graft outcome. An international guidelines has recommended the target C2 over time-course post-transplantation. We determined whether this recommendation is appropriate for our patients who are Asian ethnic. The clinical data of these C2 monitoring kidney transplant recipients were compared with the historical cohort of microemulsion CsA trough (C0) level monitoring during the first 24-month post-transplantation. The inclusion and exclusion criteria were applied for both C2 and C0 cohorts. The mean target C2 concentrations at 1, 3, 6, and 12-month post-transplantation were achieved in the C2 cohort as the international guildlines. At 3-month post-transplantation, patients who had C2 concentrations over 1500 ng/mL had higher serum creatinine as compared with those who had C2 levels<1300 ng/mL (2.23 ± 0.8 vs. 1.44 ± 0.38 mg/dL: p = 0.01). Also, at 6-month post-transplantation, patients who had C2 concentrations over 1300 ng/mL had higher serum creatinine (1.96 ± 0.29 vs. 1.37 ± 0.34 mg/dL: p < 0.01) as compared with those who had C2 levels<1100 ng/mL. There was no statistical difference of acute rejection episodes between the two cohorts. The international consensus for C2 concentraion may be too high for Asian ethnic kidney transplant recipients. The data from this study indicated lower than recommended C2 concentraion as an appropriate C2 target concentraion. [ABSTRACT FROM AUTHOR]

Tuberculosis is the most common opportunistic infection in individuals with HIV, and rifampicin is crucial in the treatment of tuberculosis. Drug–drug interactions complicate the use of DTG in HIV/TB co‐infection, which makes drug administration more difficult. This study aimed to develop the population pharmacokinetic model of DTG when co‐administered with rifampicin. The developed model was further used to investigate different dosing regimens. Forty HIV/TB‐co‐infected participants receiving DTG 50 mg once daily (OD) with food or DTG 50 mg twice daily (b.i.d.) without food were included in the analysis. Intensive pharmacokinetic samples were collected. The data were analyzed using a nonlinear mixed‐effects modeling approach. A total of 332 DTG concentrations from 40 PLWH were analyzed. The pharmacokinetics of DTG co‐administered with rifampicin can be best described by a one‐compartment model with first‐order absorption (incorporating lag time) and elimination. Total bilirubin was the only covariate that significantly affected CL/F. DTG 50 mg b.i.d. results in the highest proportion of individuals achieving in vitro IC90 of 0.064 mg/L and in vivo EC90 of 0.3 mg/L, while more than 90% of individuals receiving DTG 100 mg OD would achieve the in vitro IC90 target. Therefore, DTG 100 mg OD could serve as an alternative regimen by minimizing the difficulty of drug administration. However, its clinical efficacy requires additional evaluation. [ABSTRACT FROM AUTHOR]

The article focuses on a study conducted on the prevalence of tuberculosis (TB) and its treatment outcomes in HIV-infected patients in the Asia-Pacific region. Also includes information on the biostatistical data performed for TB diagnosis and associated survival probability in the patient with and without smoking habits.

Introduction: Cotrimoxazole (CTX) is recommended as prophylaxis against Pneumocystis jiroveci pneumonia, malaria and other serious bacterial infections in HIV‐infected patients. Despite its in vitro activity against Mycobacterium tuberculosis, the effects of CTX preventive therapy on tuberculosis (TB) remain unclear. Methods: Adults living with HIV enrolled in a regional observational cohort in Asia who had initiated combination antiretroviral therapy (cART) were included in the analysis. Factors associated with new TB diagnoses after cohort entry and survival after cART initiation were analysed using Cox regression, stratified by site. Results: A total of 7355 patients from 12 countries enrolled into the cohort between 2003 and 2016 were included in the study. There were 368 reported cases of TB after cohort entry with an incidence rate of 0.99 per 100 person‐years (/100 pys). Multivariate analyses adjusted for viral load (VL), CD4 count, body mass index (BMI) and cART duration showed that CTX reduced the hazard for new TB infection by 28% (HR 0.72, 95% CI l 0.56, 0.93). Mortality after cART initiation was 0.85/100 pys, with a median follow‐up time of 4.63 years. Predictors of survival included age, female sex, hepatitis C co‐infection, TB diagnosis, HIV VL, CD4 count and BMI. Conclusions: CTX was associated with a reduction in the hazard for new TB infection but did not impact survival in our Asian cohort. The potential preventive effect of CTX against TB during periods of severe immunosuppression should be further explored. [ABSTRACT FROM AUTHOR]