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Background Tenofovir alafenamide (TAF), a novel prodrug of tenofovir (TFV), has become the preferred drug for the treatment of HIV-1 and chronic hepatitis B infection in clinical practice. Results from clinical trials showed that it had better renal and bone mineral outcomes compared to tenofovir disoproxil fumarate (TDF). However, as we have seen with TDF, side effects from the new medication can be more prevalent and recognized after extensive use in real world situations. Sporadic cases of acute kidney injury in patients using TAF have started to emerge. Case presentation We report a case of 49-year-old Thai, HIV treatment-experienced female with hypertension presented with worsening renal function after switching her antiretroviral regimen from TDF, emtricitabine (FTC), and lopinavir/ritonavir (LPV/r) to TAF, FTC and dolutegravir (DTG) for 3 months. Kidney biopsy showed distinctive picture of tenofovir nephrotoxicity with acute tubular injury and mitochondrial injury. The possible causes of acute kidney injury and nephrotoxicity from TAF for this patient were discussed. We have extensively reviewed all published case reports of TAF-associated nephrotoxicity and summarized the essential information in this article. Conclusion Although TAF has less nephrotoxicity compared with TDF; renal function should always be monitored after the initiation of both drugs. Future large cohort studies are required to identify the risk factors of TAF-associated nephrotoxicity and to design an effective preventive strategy.

OBJECTIVES We investigated the incidence and associated factors of liver cirrhosis and cardiovascular disease risks among people living with HIV (PLHIV) in a Thai cohort. DESIGN A prospective cohort analysis. METHODS Participants with at least one reliable transient elastography measurement during follow-up, who had pretreatment alanine transaminase, AST, and platelet count at HIV treatment initiation were included. Liver cirrhosis was defined as AST to Platelet Ratio Index >1.5 or fibrosis-4 (FIB-4) >3.25 or liver stiffness by transient elastography >12.5 kPa and confirmed by imaging or liver biopsy. Competing-risk regression was used to identify factors associated with liver cirrhosis. Time-updated 10-year atherosclerotic CVD (ASCVD) risks were compared between PLHIV with or without liver cirrhosis. RESULTS A total of 1069 participants (33% women, 9% hepatitis C virus, and 16% hepatitis B virus) with the median age and CD4 at cART initiation of 32 years and 240 cells/mm3 were included. During 8232 person-years, 124 (12%) developed liver cirrhosis after a median of 6.9 (2.4-13.7) follow-up years [incidence, 1.5 (95% confidence interval: 1.3 to 1.8) per 100 person-years]. In multivariable analysis, the factors independently associated with liver cirrhosis were time-updated HIV viremia, hepatitis B virus, and hepatitis C virus coinfection, diabetes mellitus, high-density lipoproteins

BACKGROUND This population pharmacokinetic-pharmacogenetic study aimed to investigate the optimal dose of RTV-boosted ATV (ATV/RTV) for Thai adult HIV-infected patients. METHODS A total of 1460 concentrations of ATV and RTV from 544 patients receiving an ATV/RTV-based regimen were analyzed. The CYP3A5 6986 A > G, ABCB1 3435 C > T, ABCB1 2677 G > T, SLCO1B1 521 T > C, and NR1I2 63396 C > T were genotyped. A population pharmacokinetic model was performed using a nonlinear mixed-effect model (NONMEM®). Monte Carlo simulations were conducted to compare the percentages of patients achieving the therapeutic range of ATV through concentrations (Ctrough). RESULTS The apparent oral clearance of ATV (CL/FATV) without RTV was 7.69 L/h with interindividual variability (IIV) of 28.7%. Patients with CYP3A5 6986 GG had a 7.1% lower CL/FATV than those with AA or AG genotype. The CL/FATV decreased by 10.8% for females compared with males. Simulation results showed higher percentages (~70%) of patient receiving doses of 200/100 or 200/50 mg achieved the target ATV Ctrough, while more patients (~40%) receiving a standard dose (300/100 mg) had ATV Ctrough above this target. CONCLUSIONS Both CYP3A5 6986 A > G and female decreased CL/FATV in Thai HIV-infected patients. Simulations supported that the reduced dose of ATV/RTV was sufficient to achieve the target concentration for Thai population.

Objectives We investigated weight changes following antiretroviral therapy (ART) initiation, the development of metabolic syndrome (MetS) and its association with all-cause mortality among Asian adults living with HIV. Methods Participants enrolled in a regional Asian HIV-infected cohort with weight and height measurements at ART initiation were eligible for inclusion in the analysis. Factors associated with weight changes and incident MetS (according to the International Diabetic Federation (IDF) definition) were analysed using linear mixed models and Cox regression, respectively. Competing-risk regression models were used to investigate the association of MetS with all-cause mortality. Results Among 4931 people living with HIV (PLWH), 66% were male. At ART initiation, the median age was 34 [interquartile range (IQR) 29-41] years, and the median (IQR) weight and body mass index (BMI) were 55 (48-63) kg and 20.5 (18.4-22.9) kg/m2 , respectively. At 1, 2 and 3 years of ART, overall mean (± standard deviation) weight gain was 2.2 (±5.3), 3.0 (±6.2) and 3.7 (±6.5) kg, respectively. Participants with baseline CD4 count ≤ 200 cells/µL [weight difference (diff) = 2.2 kg; 95% confidence interval (CI) 1.9-2.5 kg] and baseline HIV RNA ≥ 100 000 HIV-1 RNA copies/mL (diff = 0.6 kg; 95% CI 0.2-1.0 kg), and those starting with integrase strand transfer inhibitor (INSTI)-based ART (diff = 2.1 kg; 95% CI 0.7-3.5 kg vs. nonnucleoside reverse transcriptase inhibitors) had greater weight gain. After exclusion of those with abnormal baseline levels of MetS components, 295/3503 had incident MetS [1.18 (95% CI 1.05-1.32)/100 person-years (PY)]. The mortality rate was 0.7 (95% CI 0.6-0.8)/100 PY. MetS was not significantly associated with all-cause mortality in the adjusted model (P = 0.236). Conclusions Weight gain after ART initiation was significantly higher among those initiating ART with lower CD4 count, higher HIV RNA and an INSTI-based regimen after controlling for baseline BMI. Greater efforts to identify and manage MetS among PLWH are needed.

BACKGROUND: Diagnostic tools to identify incipient or subclinical TB stages will be helpful for preventive intervention. A simple biomarker to predict TB may be the monocytes to lymphocytes ratio (ML ratio) in peripheral blood.METHODS: We assessed the relationship between multiple time-updated ML ratio measurements and incidence of TB in people living with HIV (PLWH) after antiretroviral therapy (ART) was initiated. The ML ratio was updated at least every 6 months. TB incidence with corresponding 95% confidence intervals stratified according to time-updated ML ratio was calculated using ML ratio in quartiles.RESULTS: A total of 1305 PLWH were included in the analyses: 46 had incident TB and 1259 remained TB-free. The TB incidence rate was 10.3 (95% CI 7.1–14.9) cases/1000 patient-years (PYR) among participants with ML ratio ≥0.25 compared with 1.1/1000 PYR (95% CI 0.4–2.9) among those with ML ratio CONCLUSION: Increased ML ratio was predictive of incident TB among PLWH on or after ART. The ML ratio can be a simple tool to stratify the risk of TB in PLWH.

In low-income and middle-income countries, affordable direct-acting antivirals are urgently needed to treat hepatitis C virus (HCV) infection. The combination of ravidasvir, a pangenotypic non-structural protein 5A (NS5A) inhibitor, and sofosbuvir has shown efficacy and safety in patients with chronic HCV genotype 4 infection. STORM-C-1 trial aimed to assess the efficacy and safety of ravidasvir plus sofosbuvir in a diverse population of adults chronically infected with HCV.STORM-C-1 is a two-stage, open-label, phase 2/3 single-arm clinical trial in six public academic and non-academic centres in Malaysia and four public academic and non-academic centres in Thailand. Patients with HCV with compensated cirrhosis (Metavir F4 and Child-Turcotte-Pugh class A) or without cirrhosis (Metavir F0-3) aged 18-69 years were eligible to participate, regardless of HCV genotype, HIV infection status, previous interferon-based HCV treatment, or source of HCV infection. Once daily ravidasvir (200 mg) and sofosbuvir (400 mg) were prescribed for 12 weeks for patients without cirrhosis and for 24 weeks for those with cirrhosis. The primary endpoint was sustained virological response at 12 weeks after treatment (SVR12; defined as HCV RNA12 IU/mL in Thailand and HCV RNA15 IU/mL in Malaysia at 12 weeks after the end of treatment). This trial is registered with ClinicalTrials.gov, number NCT02961426, and the National Medical Research Register of Malaysia, NMRR-16-747-29183.Between Sept 14, 2016, and June 5, 2017, 301 patients were enrolled in stage one of STORM-C-1. 98 (33%) patients had genotype 1a infection, 27 (9%) had genotype 1b infection, two (1%) had genotype 2 infection, 158 (52%) had genotype 3 infection, and 16 (5%) had genotype 6 infection. 81 (27%) patients had compensated cirrhosis, 90 (30%) had HIV co-infection, and 99 (33%) had received previous interferon-based treatment. The most common treatment-emergent adverse events were pyrexia (35 [12%]), cough (26 [9%]), upper respiratory tract infection (23 [8%]), and headache (20 [7%]). There were no deaths or treatment discontinuations due to serious adverse events related to study drugs. Of the 300 patients included in the full analysis set, 291 (97%; 95% CI 94-99) had SVR12. Of note, SVR12 was reported in 78 (96%) of 81 patients with cirrhosis and 153 (97%) of 158 patients with genotype 3 infection, including 51 (96%) of 53 patients with cirrhosis. There was no difference in SVR12 rates by HIV co-infection or previous interferon treatment.In this first stage, ravidasvir plus sofosbuvir was effective and well tolerated in this diverse adult population of patients with chronic HCV infection. Ravidasvir plus sofosbuvir has the potential to provide an additional affordable, simple, and efficacious public health tool for large-scale implementation to eliminate HCV as a cause of morbidity and mortality.National Science and Technology Development Agency, Thailand; Department of Disease Control, Ministry of Public Health, Thailand; Ministry of Health, Malaysia; UK Aid; Médecins Sans Frontières (MSF); MSF Transformational Investment Capacity; FIND; Pharmaniaga; Starr International Foundation; Foundation for Art, Research, Partnership and Education; and the Swiss Agency for Development and Cooperation.

BACKGROUND We validated the Data collection on Adverse events of anti-HIV Drugs (D:A:D) full-risk and short-risk score models for chronic kidney disease (CKD) in the Asian HIV cohorts. SETTINGS A validation study among people living with HIV (PLHIV) aged ≥18 years among the cohorts in the Asia-Pacific region. METHODS PLHIV with a baseline estimated glomerular filtration rate > 60 mL/min/1.73 m were included for validation of the D:A:D CKD full version and short version without cardiovascular risk factors. Those with

Objective Statins play a critical role in reducing the elevated risk of atherosclerotic cardiovascular disease (ASCVD) among people living with HIV (PLHIV). However, maintaining statin therapy is difficult and may be impeded further in PLHIV due to the risk of antiretroviral therapy/statin interactions. We estimated rates of statin discontinuation and re-initiation, and the percentage of days covered by statin use among PLHIV on antiretroviral therapy, and investigated factors associated with these outcomes. Design Observational cohort study. Methods Clinical data from individuals attending the HIV-NAT Centre in Bangkok, Thailand between 2001-2020 were analyzed using Kaplan-Meier curves, competing-risk regression, and generalized estimating equations. Discontinuation was defined as statin cessation lasting 90 days. Results Data on 318 PLHIV were included. After one, three and five years, 22.3%, 50.8% and 61.1% had discontinued statin use, respectively. Among those who discontinued (n = 178), 52.0% re-initiated statin use within five years. Factors associated with statin discontinuation were low education level, fewer concomitant medications, and lack of ASCVD. Factors associated with statin re-initiation were older age, diabetes, and high levels of low-density lipoprotein cholesterol. The adjusted mean percentage of days covered by a statin was 86.7%, 61.1% and 58.1% in the six months prior to one, three and five years of follow-up, respectively. Conclusions Maintenance of statin therapy is poor among PLHIV on antiretroviral therapy but is not associated with using contraindicated antiretroviral/statin combinations. A better understanding of statin use in PLHIV will aid clinicians treating individuals and policy makers designing interventions for population-level ASCVD risk reduction.

BACKGROUND: Tenofovir disoproxil fumarate (TDF) is effective in suppressing HIV and hepatitis B virus (HBV) replication in HIV-HBV coinfection although HBV DNA can persist in some individuals on TDF-containing antiretroviral therapy (ART). We initiated a prospective longitudinal study to determine durability of HBV virological control and clinical outcomes after prolonged TDF-based ART in HIV-HBV coinfection. METHODS: Ninety-two HIV-HBV coinfected participants on, or about to commence, TDF-containing ART from Australia (n = 41) and Thailand (n = 52) were enrolled. Participants were followed 6-monthly for 2 years, then annually to 5 years. Laboratory and clinical assessments and a serum sample were collected at each study visit. These analyses compare follow-up at 2 and 5 years. RESULTS: 12.0% (95% confidence interval 6.8 to 20.2) of total study entry cohort (n = 92) or 15.3% (95% confidence interval: 8.8 to 25.3) of those with data to year 5 (n = 72) lost hepatitis B surface antigen (HBsAg). The only statistically significant association with HBsAg loss was lower study entry quantitative HBsAg. CD4 T-cell count increased by a median 245 cells/mm3 between the preTDF sample and 5 years of follow-up. By year 5, 98.5% of the cohort had undetectable HBV DNA (

Background Several kidney transplantation (KT) prediction models for patient and graft outcomes have been developed based on Caucasian populations. However, KT in Asian countries differs due to patient characteristics and practices. To date, there has been no equation developed for predicting outcomes among Asian KT recipients. Methods We developed equations for predicting 5- and 10-year patient survival (PS) and death-censored graft survival (DCGS) based on 6662 patients in the Thai Transplant Registry. The cohort was divided into training and validation data sets. We identified factors significantly associated with outcomes by Cox regression. In the validation data set, we also compared our models with another model based on KT in the United States. Results Variables included for developing the DCGS and PS models were recipient and donor age, background kidney disease, dialysis vintage, donor hepatitis C virus status, cardiovascular diseases, panel reactive antibody, donor types, donor creatinine, ischemic time, and immunosuppression regimens. The C statistics of our model in the validation data set were 0.69 (0.66-0.71) and 0.64 (0.59-0.68) for DCGS and PS. Our model performed better when compared with a model based on US patients. Compared with tacrolimus, KT recipients aged ≤44 years receiving cyclosporine A had a higher risk of graft loss (adjusted hazard ratio = 1.26; P = 0.046). The risk of death was higher in recipients aged >44 years and taking cyclosporine A (adjusted hazard ratio = 1.44; P = 0.011). Conclusions Our prediction model is the first based on an Asian population, can be used immediately after transplantation. The model can be accessed at www.nephrochula.com/ktmodels.

The Bangkok International Symposium on HIV Medicine is one of the longest running and largest international conferences in the Asia–Pacific, providing healthcare workers with the most up-to-date information pertaining to HIV and coinfections. In the third week of January 2020, 500 HIV researchers and service providers from over 21 countries worldwide gathered in Bangkok to share data and experiences in the treatment and prevention of HIV, TB and sexually transmitted infections. Highlights of the 2020 symposium included a roundtable discussion of pre-exposure prophylaxis, a 1-day forum on TB, the potential for a HBV cure and, for the first time, oral presentations from four young investigators from the region.

Objectives Integration of HIV and non-communicable disease services improves the quality and efficiency of care in low- and middle-income countries (LMICs). We aimed to describe current practices for the screening and management of atherosclerotic cardiovascular disease (ASCVD) among adult HIV clinics in Asia. Methods Sixteen LMIC sites included in the International Epidemiology Databases to Evaluate AIDS - Asia-Pacific network were surveyed. Results Sites were mostly (81%) based in urban public referral hospitals. Half had protocols to assess tobacco and alcohol use. Protocols for assessing physical inactivity and obesity were in place at 31% and 38% of sites, respectively. Most sites provided educational material on ASCVD risk factors (between 56% and 75% depending on risk factors). A total of 94% reported performing routine screening for hypertension, 100% for hyperlipidaemia and 88% for diabetes. Routine ASCVD risk assessment was reported by 94% of sites. Protocols for the management of hypertension, hyperlipidaemia, diabetes, high ASCVD risk and chronic ischaemic stroke were in place at 50%, 69%, 56%, 19% and 38% of sites, respectively. Blood pressure monitoring was free for patients at 69% of sites; however, most required patients to pay some or all the costs for other ASCVD-related procedures. Medications available in the clinic or within the same facility included angiotensin-converting enzyme inhibitors (81%), statins (94%) and sulphonylureas (94%). Conclusion The consistent availability of clinical screening, diagnostic testing and procedures and the availability of ASCVD medications in the Asian LMIC clinics surveyed are strengths that should be leveraged to improve the implementation of cardiovascular care protocols.

BACKGROUND: The Randomized Trial to Prevent Vascular Events in HIV (REPRIEVE) is a multicenter, randomized, placebo-controlled trial, designed to test whether a statin medication can prevent cardiovascular disease in people with HIV. REPRIEVE recently completed enrollment of 7557 participants at over 100 clinical sites globally. Participant groups of focus were women, and racial and ethnic minorities. OBJECTIVE: To describe recruitment methods and strategies developed by the REPRIEVE Clinical Coordinating Center (CCC) and share best practices learned from the recruitment process. METHODS: Enrollment targets were agreed upon with the primary funder, the National Heart, Lung, and Blood Institute (NHLBI) and were milestone driven. Milestones included number of sites activated, number of participants enrolled within specific time frames, and proportion of women and minorities enrolled. Strategies to achieve these milestones and included structured interviews with site-designated REPRIEVE Recruitment Champions to develop best practices, development of a multimedia campaign, and site level recruitment support. RESULTS: Recruitment initiated March, 2015 and completed March, 2019. The final accrual target was 7500 participants over 48 months. The trial met this target within the time specified. Overall, 10,613 screens were completed, 48% of participants enrolled from sites outside of North America, 32% were female, 44% were black or African American, and 25% were Hispanic or Latino. CONCLUSIONS: REPRIEVE met its overall projected recruitment goal by using multiple, simultaneous strategies to specifically target a diverse population including minority subgroups. REPRIEVE benefited from the development of recruitment strategies with clear targets and communication of accrual targets to study teams.

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 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) 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.

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

Kidney transplantation recipients (KTR) with coronavirus disease 2019 (COVID-19) are at higher risk of death than general population. However, mortality risk factors in KTR are still not clearly identified. Our objective was to systematically analyze published evidence for risk factors associated with mortality in COVID-19 KTR. Electronic databases were searched for eligible studies on 1 August 2021. All prospective and retrospective studies of COVID-19 in KTR were considered eligible without language restriction. Since data in case reports and series could potentially be subsets of larger studies, only studies with ≥ 50 patients were included. Random-effects model meta-analysis was used to calculate weighted mean difference (WMD) and pooled odds ratio (OR) of factors associated with mortality. From a total 1,137 articles retrieved, 13 were included in the systematic review and meta-analysis comprising 4,440 KTR. Compared with survivors, non-survivors were significantly older (WMD 10.5 years, 95% CI 9.3–11.8). KTR of deceased donor were at higher risk of death (OR 1.73, 95% CI 1.10–2.74). Comorbidities including diabetes mellitus, cardiovascular disease, and active cancer significantly increased mortality risk. KTR with dyspnea (OR 5.68, 95% CI 2.11–15.33) and pneumonia (OR 10.64, 95% CI 3.37–33.55) at presentation were at higher mortality risk, while diarrhea decreased the risk (OR 0.61, 95% CI 0.47–0.78). Acute kidney injury was associated with mortality (OR 3.24, 95% CI 1.36–7.70). Inflammatory markers were significantly higher in the non-survivors, including C-reactive protein, procalcitonin, and interleukine-6. A number of COVID-19 mortality risk factors were identified from KTR patient characteristics, presenting symptoms, and laboratory investigations. KTR with these risk factors should receive more intensive monitoring and early therapeutic interventions to optimize health outcomes.

BackgroundPeople living with HIV (PLHIV) have an elevated risk of atherosclerotic cardiovascular disease (ASCVD) compared to their uninfected peers. Expanding statin use may help alleviate this burden. We evaluated the cost-effectiveness of reducing the recommend statin initiation threshold for primary ASCVD prevention among PLHIV in Thailand.MethodsOur decision analytic microsimulation model randomly selected (with replacement) individuals from the TREAT Asia HIV Observational Database (data collected between 1/January/2013 and 1/September/2019). Direct medical costs and quality-adjusted life-years were assigned in annual cycles over a lifetime horizon and discounted at 3% per year. We assumed the Thai healthcare sector perspective. The study population included PLHIV aged 35–75 years, without ASCVD, and receiving antiretroviral therapy. Statin initiation thresholds evaluated were 10-year ASCVD risk ≥10% (control), ≥7.5% and ≥5%.ResultsA statin initiation threshold of ASCVD risk ≥7.5% resulted in accumulation of 0.015 additional quality-adjusted life-years compared with an ASCVD risk threshold ≥10%, at an extra cost of 3,539 Baht ($US113), giving an incremental cost-effectiveness ratio of 239,000 Baht ($US7,670)/quality-adjusted life-year gained. The incremental cost-effectiveness ratio comparing ASCVD risk ≥5% to ≥7.5% was 349,000 Baht ($US11,200)/quality-adjusted life-year gained. At a willingness-to-pay threshold of 160,000 Baht ($US5,135)/quality-adjusted life-year gained, a 30.8% reduction in the average cost of low/moderate statin therapy led to the ASCVD risk threshold ≥7.5% becoming cost-effective compared with current practice.ConclusionsReducing the recommended 10-year ASCVD risk threshold for statin initiation among PLHIV in Thailand would not currently be cost-effective. However, a lower threshold could become cost-effective with greater preference for cheaper statins.

Background: Ageing and chronic kidney disease (CKD) affect pharmacokinetic (PK) parameters. Since mechanisms are related and remain unclear, cytochrome P450 (CYP) 3A and drug transporter activities were investigated in the elderly with or without CKD and compared to healthy adults using a microdose cocktail.Methods: Healthy young participants (n = 20), healthy elderly participants (n = 16) and elderly patients with CKD (n = 17) received, in study period 1, a single dose of microdose cocktail probe containing 30 µg midazolam, 750 µg dabigatran etexilate, 100 µg atorvastatin, 10 µg pitavastatin, and 50 µg rosuvastatin. After a 14-day wash-out period, healthy young participants continued to study period 2 with the microdose cocktail plus rifampicin. PK parameters including area under the plasma concentration-time curve (AUC), maximum plasma drug concentration (Cmax), and half-life were estimated before making pairwise comparisons of geometric mean ratios (GMR) between groups.Results: AUC and Cmax GMR (95% confidence interval; CI) of midazolam, a CYP3A probe substrate, were increased 2.30 (1.70–3.09) and 2.90 (2.16–3.88) fold in healthy elderly and elderly patients with CKD, respectively, together with a prolonged half-life. AUC and Cmax GMR (95%CI) of atorvastatin, another CYP3A substrate, was increased 2.14 (1.52–3.02) fold in healthy elderly and 4.15 (2.98–5.79) fold in elderly patients with CKD, indicating decreased CYP3A activity related to ageing. Associated AUC changes in the probe drug whose activity could be modified by intestinal P-glycoprotein (P-gp) activity, dabigatran etexilate, were observed in patients with CKD. However, whether the activity of pitavastatin and rosuvastatin is modified by organic anion transporting polypeptide 1B (OATP1B) and of breast cancer resistance protein (BCRP), respectively, in elderly participants with or without CKD was inconclusive.Conclusions: CYP3A activity is reduced in ageing. Intestinal P-gp function might be affected by CKD, but further confirmation appears warranted.Clinical Trial Registration:http://www.thaiclinicaltrials.org/ (TCTR 20180312002 registered on March 07, 2018)

Background: Currently, there is a lack of evidence to guide the optimal care for post-acute kidney injury (AKI) survivors. Therefore, post-discharge care by a multidisciplinary care team (MDCT) may improve these outcomes. This study aimed to demonstrate the outcomes of implementing comprehensive care by a MDCT in post-severe AKI survivors.Methods: This study was a randomized controlled trial conducted between August 2018 to January 2021. Patients who survived severe AKI stage 2-3 were enrolled and randomized to be followed up with either comprehensive or standard care for 12 months. The comprehensive post-AKI care integrated a MDCT (nephrologists, nurses, nutritionists, and pharmacists). The primary outcome was the feasibility outcomes, comprised of the rates of loss to follow up, specialist consultation, 3-d dietary record, drug reconciliation, and drug alert rates at 12 months. Secondary outcomes included major adverse kidney events, estimated glomerular filtration rate (eGFR), and amount of albuminuria at 12 months. Results: Ninety-eight AKI stage 3 survivors were enrolled, and randomized into comprehensive care and standard care groups (49 patients in each group). Compared to the standard care group, the comprehensive care group had significantly better in feasibility outcomes; higher rates of specialist consultation, 3-d dietary record, drug reconciliation, and drug alerts (p < 0.001). The mean eGFR at 12 months were comparable between the two groups (66.74 vs. 61.12 mL/min/1.73 m2, p = 0.54). The urine albumin: creatinine ratio (UACR) was significantly lower in the comprehensive care group (36.83 vs. 177.70 mg/g, p = 0.036), while the blood pressure control was also better in the comprehensive care group (87.9% vs. 57.5%, p = 0.006). There was no difference in the other renal outcomes between the two groups.Conclusions: Comprehensive care by a MDCT is feasible and could be implemented for post-severe AKI survivors. These resulted in a better reduction in the UACR and better blood pressure control. Trial registration: clinicaltrial.gov: NCT04012008 (First registered July 9, 2019)

Objective This study aimed to compare treatment outcomes and factors associated with mortality in HIV-1-positive and HIV-1-negative individuals. Methods We conducted a cohort study between July 2008 and December 2016. Logistic regression was used to determine factors associated with outcomes and death after tuberculosis (TB) treatment. Results A total of 996 individuals with TB, 228 (22.9%) with HIV-1 co-infection and 770 (77.1%) who were HIV-1 negative were reviewed. The overall treatment success rate was 74.3%. The HIV-1-negative individuals with TB had significantly higher treatment success rates (77.2% vs 64.5%, P > 0.001). Using logistic regression analysis, age >50 years (adjusted odds ratio [aOR] 3.89, 95% confidence interval [CI] 2.24–6.76; P > 0.001), body weight ≤45 kg (aOR 2.19, 95% CI 1.14–4.19; P = 0.02) and HIV-1-positive status (aOR 3.31, 95% CI 1.84–5.91; P > 0.001) were independently associated with death during TB treatment. Among HIV-1-positive individuals, not undergoing antiretroviral therapy (ART), having diabetes and a CD4 T cell count of >50 cells/mm3 were significantly associated with death. Conclusion Individuals who had both TB and HIV-1 in Thailand had lower TB treatment success and higher mortality rates compared with individuals with TB without HIV-1. Strategies to improve ART uptake and to reduce risk of developing active TB among individuals with advanced HIV-1 infection should be scaled up.

BACKGROUND Patients on dialysis are at risk of hepatitis B virus (HBV) infection, and antibodies against the hepatitis B surface antigen (anti-HBs) ≥ 10 IU/L are required. However, a high percentages of HBV vaccine nonresponders have been reported. We aimed to determine the optimal HBV vaccination protocol. MATERIALS AND METHODS Kidney transplant waitlisted patients were followed for 12 months and categorized into two groups. Group A included patients with sustained anti-HBs ≥ 10 IU/L who did not require vaccination. Group B consisted of patients with anti-HBs < 10 IU/L who were treated with a course of 4 double-dose HBV vaccinations. Without seroconversion after the first course, a second course was initiated. A third course, coadministered with the tetanus-diphtheria (Td) vaccine, was performed upon failure of the second course. RESULTS A total of 266 patients were included, 140 were categorized into group A and 126 into group B. Higher serum phosphorus, hemoglobin, and antibodies against the hepatitis core antigen (anti-HBc) were associated with sustaining anti-HBs ≥ 10 IU/L without vaccination. Diabetes mellitus (DM) was associated with the need for vaccination. For group B, 107 patients required 1 course of vaccination, 15 patients required 2 courses, and 4 patients required the third course with Td vaccine coadministration. Long dialysis vintage and low hemoglobin level were associated with seroconversion failure after the first course. CONCLUSION Serum phosphorus, hemoglobin, DM, anti-HBc, and dialysis vintage were associated with the anti-HBs seroresponsiveness and sustainability. Our 3-course of 4 double-dose HBV vaccines regimen (with Td vaccine in the final course) conferred immunity to all patients.

Many people living with HIV (PLWH) are aging with geriatric syndromes, but few undergo comprehensive geriatric assessment (CGA) due to limited resources. Our study evaluates tools to identify aging PLWH who may forego CGA. We conducted a cross-sectional study on 357 PLWH ≥50 years old at the Red Cross, Thailand. Tools evaluated were the Veterans Aging Cohort Study Index (VACSI) and G-8, which is predictive among older cancer patients. CGA consists of eight tests: history of fall within 12 months, timed-up-and-go test (TUG), activities of daily living (ADL), instrumental ADL (IADL), Montreal cognitive assessment (MoCA), Thai depression scale (TDS), mini nutritional assessment (MNA), and HIV symptom index (HSI). We considered ≥2 impaired domains on CGA to be abnormal results. Forty-nine percent (n = 175) had ≥2 impaired domains on CGA. Few participants had experienced a fall (11%) or abnormal TUG/ADL/IADL ( 15.5 produces 90%Se and 33%Sp (AUC = 74, 95%CI 69–79) in identifying patients with 13.5 produces 91%Se and 77%Sp (AUC = 89, 95%CI 86–92) in ruling out abnormal nutrition. Patients with VACSI 15.5 may forego CGA due to low likelihood of abnormal cognition, mood, nutrition, or symptom burden.

Background Duration of viral shedding is a determinant of infectivity and transmissibility, but few data exist about oseltamivir's ability to alter viral shedding. Methods From January 2012 through October 2017, a randomized, double-blinded multicenter clinical trial was conducted in adults aged 18–64 years at 42 sites in Thailand, the United States, and Argentina. Participants with influenza A or B and without risk factors for complications of influenza were screened for the study. Eligible participants were randomized to receive oseltamivir 75 mg or placebo twice daily for 5 days. The primary endpoint was the percentage of participants with virus detectable by polymerase chain reaction in nasopharyngeal swab at day 3. Results Of 716 adults screened for the study, 558 were randomized, and 501 were confirmed to have influenza. Forty-six participants in the pilot study were excluded, and 449 of the 455 participants in the population for the primary analysis had day 3 viral shedding results. Ninety-nine (45.0%) of 220 participants in the oseltamivir arm had virus detected at day 3 compared with 131 (57.2%) of 229 participants in the placebo arm (absolute difference of −12.2% [−21.4%, −3.0%], P =; .010). The median time to alleviation of symptoms was 79.0 hours for the oseltamivir arm and 84.0 hours for the placebo arm (P =; .34) in those with confirmed influenza infection. Conclusions Oseltamivir decreased viral shedding in this low-risk population. However, in the population enrolled in this study, it did not significantly decrease the time to resolution of clinical symptoms. Clinical Trials Registration NCT01314911.

Background The effects of mycophenolic acid exposure in the early period after transplantation on clinical outcomes have been reported; however, mycophenolic acid exposure in the early period after transplantation in Asian kidney transplant recipients who receive 1.5 g/d mycophenolate mofetil has never been investigated. Objective To determine mycophenolic acid exposure on day 3 post-transplantation in kidney transplant recipiens who receive 1.5 g/d mycophenolate mofetil. The effects of the reduced renal function on mycophenolic acid area under the concentration–time curve (AUC) and the achievement of the target AUC on the incidence of biopsy proven acute rejection during the first month post-transplantation were also evaluated. Setting A university hospital Method Blood samples and 24-h urine were collected on day 3 post-transplantation. Main outcome measures The mycophenolic acid AUC was calculated by linear trapezoidal rule and compared with the target of 45 mg*h/L. Results Of 42 Thai kidney transplant recipiens, the mean mycophenolic acid AUC of 45.1 mg*h/L (SD 14.7) was comparable to the AUC target (P = 0.962). Significant differences of the mycophenolic acid AUC were observed between patients with urine output of

Aim: To evaluate the influence of genetic polymorphisms on plasma trough concentrations of atazanavir (ATV) and ritonavir (RTV). Patients & methods: The concentration-to-dose ratios were compared between different genotype groups of CYP3A5, ABCB1, SLCO1B1 and NR1I2 in 490 patients. Multiple regression analysis was used to examine the association between genetic and clinical factors and log-transformed concentration-to-dose ratio of ATV and RTV. Results: Higher concentrations of ATV and RTV were significantly associated with CYP3A5 6986 GG and SLCO1B1 521 TC or CC. Female patients had significantly higher ATV plasma concentration than male patients. Conclusion: Genetic polymorphisms and gender are factors affecting the variability of ATV and RTV concentrations in the Thai population. Thus, genetic testing is worth considering when atazanavir + low dose ritonavir is prescribed.

Mycobacterium avium complex prophylaxis is recommended for patients with advanced HIV infection. With the decrease in incidence of disseminated Mycobacterium avium complex infection and the availability of antiretroviral therapy (ART), the benefits of macrolide prophylaxis were investigated. This study examined the impact of macrolide prophylaxis on AIDS-defining conditions and HIV-associated mortality in a cohort of HIV-infected patients on ART.Patients from TREAT Asia HIV Observational Database (September 2015 data transfer) aged 18 years and older with a CD4 count50 cells/mm at ART initiation were included. The effect of macrolide prophylaxis on HIV-associated mortality or AIDS-defining conditions (as a combined outcome) and HIV-associated mortality alone were evaluated using competing risk regression. Sensitivity analysis was conducted in patients with a CD4100 cells/mm at ART initiation.Of 1345 eligible patients, 10.6% received macrolide prophylaxis. The rate of the combined outcome was 7.35 [95% confidence interval (CI): 6.04 to 8.95] per 100 patient-years, whereas the rate of HIV-associated mortality was 3.14 (95% CI: 2.35 to 4.19) per 100 patient-years. Macrolide use was associated with a significantly decreased risk of HIV-associated mortality (hazard ratio 0.10, 95% CI: 0.01 to 0.80, P = 0.031) but not with the combined outcome (hazard ratio 0.86, 95% CI: 0.32 to 2.229, P = 0.764). Sensitivity analyses showed consistent results among patients with a CD4100 cells/mm at ART initiation.Macrolide prophylaxis is associated with improved survival among Asian HIV-infected patients with low CD4 cell counts and on ART. This study suggests the increased usage and coverage of macrolide prophylaxis among people living with HIV in Asia.

Bangkok International Symposium on HIV Medicine is the largest regional conference on clinical HIV medicine in Southeast Asia. Held annually during the third week of January and spanning 3 days, the symposium provides updates on HIV and co-infection treatment and prevention. It is sponsored by HIV Netherlands Australia Thailand Research Collaboration (HIV-NAT), the first and largest clinical research center in Thailand and region. HIV-NAT was founded by the late David Cooper, late Joep Lange and Emeritus Praphan Phanuphak, who dedicated their lives to making HIV care and treatment accessible to people living with HIV in Thailand and throughout the developing world. The symposium continues its tradition of bringing the latest information in the field of HIV medicine to healthcare professionals.

BACKGROUND: Bictegravir, coformulated with emtricitabine/tenofovir alafenamide as a fixed-dose combination (B/F/TAF), is recommended for treatment of HIV-1-infection. Multiple studies of B/F/TAF in treatment-naive and virologically suppressed cohorts have shown high efficacy and tolerability with no treatment-emergent resistance through 48 weeks. Participants in these studies have been predominantly men. We report 48-week results from a phase 3 study evaluating switching to B/F/TAF, specifically in a globally distributed trial population of women. METHODS: In this multicenter, randomized, open-label, active-controlled, noninferiority trial (ClinicalTrials.gov NCT02652624), women living with HIV who were virologically suppressed (HIV-1 RNA levels

INTRODUCTION Data on HIV treatment outcomes in people who inject drugs (PWID) in the Asia‐Pacific are sparse despite the high burden of drug use. We assessed immunological and virological responses, AIDS‐defining events and mortality among PWID receiving antiretroviral therapy (ART). METHODS We investigated HIV treatment outcomes among people who acquired HIV via injecting drug use in the TREAT Asia HIV Observational Database (TAHOD) between January 2003 and March 2019. Trends in CD4 count and viral suppression (VS, HIV viral load

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

BackgroundDrug-resistant Mycobacterium tuberculosis (Mtb) strains threaten tuberculosis (TB) control. We compared data on drug resistance obtained at clinics in seven high TB burden countries during routine care with whole-genome sequencing (WGS) carried out centrally.MethodsWe collected pulmonary Mtb isolates and clinical data from adult TB patients in Africa, Latin America, and Asia, stratified by HIV status and drug resistance, from 2013 to 2016. Participating sites performed drug susceptibility testing (DST) locally, using routinely available methods. WGS was done using Illumina HiSeq 2500 at laboratories in the USA and Switzerland. We used TBprofiler to analyse the genomes. We used multivariable logistic regression adjusted for sex, age, HIV-status, history of TB, sputum positivity, and Mtb-lineage to analyse mortality.FindingsWe included 582 TB patients. The median age was 32 years (interquartile range: 27-43 years), 225 (39%) were female, and 247 (42%) were HIV-positive. Based on WGS, 339 (58%) isolates were pan-susceptible, 35 (6%) monoresistant, 146 (25%) multidrug-resistant, and 24 (4%) pre-/ extensively drug-resistant (pre-XDR/XDR-TB). The local DST results were discordant compared to WGS results in 130/582 (22%) of patients. All testing methods identified isoniazid and rifampicin resistance with relatively high agreement (kappa 0.69 for isoniazid and 0.88 rifampicin). Resistance to ethambutol, pyrazinamide, and second-line drugs was rarely tested locally. Of 576 patients with known treatment, 86 (15%) patients received inadequate treatment according to WGS results and the World Health Organization treatment guidelines. The analysis of mortality was based on 530 patients; 63 patients (12%) died and 77 patients (15%) received inadequate treatment. Mortality ranged from 6% in patients with pan-susceptible Mtb (18/310) to 39% in patients with pre-XDR/XDR-TB (9/23). The adjusted odds ratio for mortality was 4.82 (95% CI 2.43-9.44) for under-treatment and 0.52 (95% CI 0.03-2.73) for over-treatment.InterpretationIn seven high-burden TB countries, we observed discrepancies between drug resistance patterns from local DST and WGS, which resulted in inadequate treatment and higher mortality. WGS can provide accurate and detailed drug resistance information, which is required to improve the outcomes of drug-resistant TB in high burden settings. Our results support the WHO’s call for point-of-care tests based on WGS.

BACKGROUND This study investigated the sustained virologic responses (SVRs) among prisoners with hepatitis C virus (HCV) using universal test-and-treat approach by prison health care workers in a central male prison in Thailand. METHODS A universal HCV screening was conducted in a maximum-security central prison (Klong Prem Central Prison) in Thailand. HCV RNA-confirmed prisoners were treated with generic sofosbuvir/velpatasvir by prison health care workers, regardless of their HCV genotypes and duration of prison sentences. We evaluated the SVR rates at 12 weeks after completing direct acting antivirals (DAA) treatment. RESULTS A total of 68 prisoners with detectable HCV RNA received DAA treatment. The median age and duration of prison sentences were 44 years (interquartile range, 41-53) and 25 (interquartile range, 19-33) years, respectively. Twenty-five percentage of the participants was coinfected with HIV, and 6% of the participants was coinfected with hepatitis B virus. Among all prisoners who received DAA treatment, 20 (29%) had genotype (GT)-1a, 3 (4%) had GT-1b, 22 (32%) had GT-3a, 3 (4%) had GT-3b, and 7 (10%) had GT-6. Overall, improvements in liver biomarkers were seen after HCV treatment, and SVR was achieved in 97% of the participants with per-protocol analysis and in 90% of the participants with intention-to-treat analysis. CONCLUSIONS HCV treatment using DAA among prisoners through universal test-and-treat approach led by prison health care workers is highly effective and safe, and such model can potentially help to facilitate the goals of HCV microelimination among prisoners in Thailand.

BACKGROUND: B-cell activating factor (BAFF), an essential cytokine for B lymphocytes activation, has been implicated in the pathogenesis of chronic viral hepatitis. However, the role of BAFF in patients with chronic hepatitis B (CHB) undergoing antiviral therapy is unknown. METHODS: Patients with HBeAg-positive CHB treated with 48-week pegylated interferon (PEG-IFN; n = 42), who had stored plasma samples during treatment were recruited. Serial plasma levels of BAFF and C-X-C motif chemokine 10 (CXCL10) during therapy were measured. RESULTS: Combined response (CR), defined as HBeAg seroconversion with HBV DNA < 2,000 IU/mL plus HBsAg decline ≥ 1 log10 IU/mL at 24 weeks post-treatment, was achieved in 11 (26.2%) patients. BAFF levels were elevated during treatment but decreased to pre-treatment levels after PEG-IFN cessation in both responders and non-responders. Low baseline BAFF (< 770 pg/ml) and high CXCL10 (≥ 320 pg/ml) levels were independently associated with CR in multivariate analysis. Baseline CXCL10/BAFF ratio of ≥ 0.45 was predictive of CR with positive and negative predictive values of 61.5 and 89.7%, respectively. CONCLUSIONS: In summary, low baseline BAFF and high CXCL10 levels were associated with treatment response to PEGIFN. The combined measurement of these immune markers may help individualized decision-making in patients with HBeAg-positive CHB.

BACKGROUND The transition to dolutegravir-containing antiretroviral therapy (ART) in low- and middle-income countries (LMICs) was complicated by an initial safety signal in May 2018 suggesting that exposure to dolutegravir at conception was possibly associated with infant neural tube defects. On the basis of additional evidence, in July 2019, the World Health Organization recommended dolutegravir for all adults and adolescents living with HIV. OBJECTIVE To describe dolutegravir uptake and disparities by sex and age group in LMICs. DESIGN Observational cohort study. SETTING 87 sites that began using dolutegravir in 11 LMICs in the Asia-Pacific; Caribbean, Central and South America network for HIV epidemiology (CCASAnet); and sub-Saharan African regions of the International epidemiology Databases to Evaluate AIDS (IeDEA) consortium. PATIENTS 134��672 patients aged 16 years or older who received HIV care from January 2017 through March 2020. MEASUREMENTS Sex, age group, and dolutegravir uptake (that is, newly initiating ART with dolutegravir or switching to dolutegravir from another regimen). RESULTS Differences in dolutegravir uptake among females of reproductive age (16 to 49 years) emerged after the safety signal. By the end of follow-up, the cumulative incidence of dolutegravir uptake among females 16 to 49 years old was 29.4% (95% CI, 29.0% to 29.7%) compared with 57.7% (CI, 57.2% to 58.3%) among males 16 to 49 years old. This disparity was greater in countries that began implementing dolutegravir before the safety signal and initially had highly restrictive policies versus countries with a later rollout. Dolutegravir uptake was similar among females and males aged 50 years or older. LIMITATION Follow-up was limited to 6 to 8 months after international guidelines recommended expanding access to dolutegravir. CONCLUSION Substantial disparities in dolutegravir uptake affecting females of reproductive age through early 2020 are documented. Although this disparity was anticipated because of country-level restrictions on access, the results highlight its extent and initial persistence. PRIMARY FUNDING SOURCE National Institutes of Health.

Hepatitis A virus (HAV) is able to cause a spectrum of illnesses ranging from no symptom to fulminant hepatitis which may lead to acute kidney injury. Although hepatitis A vaccine is recommended in non-immune solid organ transplant recipients who live in or travel to endemic areas, the standard 2-dose vaccination regimen demonstrated less favorable immunogenicity among these population. The 3-dose regimen showed higher response rate and immune durability in patients with human immunodeficiency virus. However, this strategy has never been studied in solid organ transplant recipients. A single-center, open-labeled, computer-based randomized controlled trial (RCT) with a 2:1 allocation ratio was conducted from August 2017 to December 2018. The study compared the seroconversion rate after receiving 2- or 3-dose regimen of hepatitis A vaccine at 0, 6 and 0, 1, 6 months, respectively, in non-immune kidney transplant recipients. A total of 401 adult kidney transplant recipients were screened for anti-HAV IgG and 285 subjects had positive results so the seroprevalence was 71.1%. Of 116 seronegative recipients, 93 (80.2%) completed vaccination; 60 and 33 participants completed 2- and 3-dose vaccination, respectively. The baseline characteristics were comparable between both groups. The seroconversion rate at 1 month after vaccination was 51.7% in the standard 2-dose regimen and 48.5% in the 3-dose regimen (p = 0.769). Overall, the seroconversion rate appeared to be associated with high estimated glomerular infiltration rate, high serum albumin, and low intensity immunosuppressive regimen. Seroconversion rate after hepatitis A vaccination in kidney transplant recipients was less favorable than healthy population. Three-dose regimen did not show superior benefit over the standard 2-dose regimen. Other strategies of immunization may increase immunogenicity among kidney transplant recipients.

OBJECTIVES Prevalence of cardiovascular disease increases with age. Little is known about the prevalence and risk factors for echocardiographic abnormalities among older people living with HIV (PLHIV) from Asia. DESIGN A cross-sectional study was conducted among PLHIV aged >50 years (N = 298) on antiretroviral treatment (ART) and HIV-negative controls (N = 100) frequency matched by sex and age in Thailand. METHODS All participants underwent standard 2-dimensional transthoracic echocardiography performed by trained cardiologists who were blinded to the participant's care and HIV status. Logistic regression was used to examine the association between cardiac abnormalities and risk factors. RESULTS The median age was 54.7 years (60.8% men) with 37.2% having hypertension and 16.6% having diabetes mellitus. PLHIV was on ART for a median of 16.2 years with current CD4 cell counts of 616 cells per cubic millimeter. Echocardiogram abnormalities did not differ among PLHIV (55%) and the controls (60%). The major abnormalities in PLHIV were following: left ventricular (LV) hypertrophy: 37% men and 42.2% women, LV systolic dysfunction (0.7%), diastolic dysfunction (24.2%), and pulmonary hypertension (3.9%). From the multivariate analyses in PLHIV, being aged >60 years was independently associated with diastolic dysfunction, whereas female sex and left atrial volume index of >34 mL/m were associated with pulmonary hypertension (P < 0.05). None of the ART was significantly associated with any major echocardiographic abnormalities. CONCLUSIONS In this long-term, well-suppressed, older, Asian PLHIV cohort, the prevalence of asymptomatic LV systolic dysfunction and pulmonary hypertension were relatively low, whereas the diastolic dysfunction and LV hypertrophy were common. Echocardiographic findings did not differ between PLHIV and HIV-uninfected controls.

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.

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.

There are limited data regarding long-term BMD changes over time among treatment-naïve people living with HIV (PLHIV) after initiating combined antiretroviral therapy (cART) in Asia. We aimed to study bone mineral density (BMD) changes among treatment-naïve PLHIV started treatment with tenofovir disoproxil fumarate (TDF)- or non-TDF-containing regimen and HIV-uninfected controls in an Asian setting. The study was a five-year prospective study. BMD at lumbar spine (LS) (L1 to L4), total hip (TH), and femoral neck (FN) were measured by dual energy X-ray absorptiometry (DEXA) scans at baseline, months 12, 24 and 60. Multivariate logistic regression models were used to explore factors associated with mean BMD ≥5% reduction after 5 years of cART. A total of 106 PLHIV (75 and 31 started TDF- and non-TDF-containing regimen, respectively) and 66 HIV-uninfected individuals were enrolled. The mean percent changes of BMD were significantly different longitudinally between TDF and non-TDF users (p

Background: In low- and middle-income countries, affordable direct-acting antivirals are urgently needed to treat hepatitis C virus (HCV) infection. The combination of ravidasvir, a pangenotypic NS5A inhibitor, and sofosbuvir has shown efficacy and safety in chronically HCV infected patients with genotype (GT) 4. The STORM-C-1 trial aims to assess the efficacy and safety of sofosbuvir plus ravidasvir in a more diverse population of adults chronically infected with HCV. Methods: STORM-C-1 is a two-stage, open-label, multicentre clinical trial in Malaysia and Thailand. HCV infected subjects with compensated cirrhosis (Metavir F4 and Child-Turcotte-Pugh class A) or without cirrhosis (Metavir F0-F3) were eligible to participate, regardless of HCV genotype, HIV infection status, prior interferon-based HCV treatment or source of HCV infection. Stage 1 results are reported here. Once-daily ravidasvir (200mg) and sofosbuvir (400mg) were prescribed for 12 (without cirrhosis) or 24 (with cirrhosis) weeks. The primary endpoint was sustained virologic response at 12 weeks post-treatment (SVR12). This trial is registered with ClinicalTrials.gov: NCT02961426 and the National Medical Research Register of Malaysia NMRR-16-747-29183. Findings: Between October 2016 and June 2017, 301 subjects were enrolled and 300 included in the full analysis set: 97 with GT1a, 27 GT1b, 2 GT2, 158 GT3, and 16 GT6; 81 (27%) had compensated cirrhosis; 90 (30%) had HIV co-infection; and 99 (33%) had prior interferon-based treatment. 291/300 subjects (97%, 95% CI 94%-99%) achieved SVR12. Three subjects prematurely discontinued study treatment due to adverse events. There were no deaths or treatment discontinuations due to the study drugs. Interpretation: In this first stage, ravidasvir plus sofosbuvir was found to be highly effective and well tolerated in all subgroups of this diverse adult population chronically infected with HCV. Trial Registration Number: This trial is registered with ClinicalTrials.gov: NCT02961426 and the National Medical Research Register of Malaysia NMRR-16-747-29183. Funding: Drugs for Neglected Diseases initiative; National Science and Technology Development Agency, Thailand; Department of Disease Control, Ministry of Public Health, Thailand; Ministry of Health, Malaysia. Conflict of Interest: Dr. Avihingsanon reports grants from National Science and Technology Development Agency (NSTDA) during the conduct of the study, and also from ViiV Healthcare outside of thesubmitted work. Tim Cressey and Nicolas Salvadori report a service agreement with DNDi.Isabelle Andrieux-Meyer, Caroline Menetrey, Francois Simon, Jean-Michel Piedagnel,Sasikala Siva, Alistair Swanson, Francois Bompart, Vishal Goyal, and Bernard Pecoul are employed by the Drugs for Neglected Diseases initiative. All other authors do not report any potential conflicts of interest. Ethical Approval: The initial protocol and all protocol amendments were reviewed and approved before implementation by the applicable individual institutional or national ethics committees. All subjects provided written informed consent.

Background The World Health Organization recommends continuation with the failing second-line regimen if third-line option is not available. We investigated treatment outcomes among people living with HIV in Asia who continued with failing second-line regimens compared with those who had treatment modifications after failure. Methods Treatment modification was defined as a change of two antiretrovirals, a drug class change or treatment interruption (TI), all for >14 days. We assessed factors associated with CD4 changes and undetectable viral load (UVL Results Of the 328 patients who failed second-line ART in our cohorts, 208 (63%) had a subsequent treatment modification. Compared with those who continued the failing regimen, the average CD4 cell increase was higher in patients who had a modification without TI (difference =77.5, 95% CI 35.3, 119.7) while no difference was observed among those with TI (difference =-5.3, 95% CI -67.3, 56.8). Compared with those who continued the failing regimen, the odds of achieving UVL was lower in patients with TI (OR=0.18, 95% CI 0.06, 0.60) and similar among those who had a modification without TI (OR=1.97, 95% CI 0.95, 4.10), with proportions of UVL 60%, 22% and 75%, respectively. Survival time was not affected by treatment modifications. Conclusions CD4 cell improvements were observed in those who had treatment modification without TI compared with those on the failing regimen. When no other options are available, maintaining the same failing ART combination provided better VL control than interrupting treatment.

BackgroundImmune restoration is often incomplete after ART in HIV patients, both quantitatively and qualitatively. We studied the incidence and probability of CD4/CD8 normalization in an adult Thai HIV cohort and explored the predictive value of the ratio for developing of non-AIDS defining events (NAEs).MethodsWe analyzed data from HIV-infected Thai adults between 1996 and 2017 in the HIV-NAT 006 prospective long-term cohort in Bangkok, Thailand. Normalization was defined as CD4/CD8 ratio ≥ 1 on two consecutive visits, and normalization probability was calculated using the Kaplan–Meier method. NAEs were a composite endpoint including cardiovascular or cerebrovascular diseases, chronic kidney diseases, non-AIDS defining malignancies and death. Multivariate Cox regression was used to evaluate demographic, disease and treatment characteristics associated with CD4/CD8 ratio normalization and NAEs.ResultsA total of 800 ART-naïve patients with baseline CD4/CD8 ratio of 3(HR: 3.62, 95% CI 2.36–5.55), p 3as reference. The second analysis explored the predictive value of CD4/CD8 ratio for NAEs. Older age (HR: 1.09, 95% CI 1.05–1.13, p 0.45 were independently associated with higher risk of progression to NAEs in the multivariate analysis.ConclusionsOur findings showed that complete immune recovery is uncommon in an Asian setting and earlier ART initiation at higher CD4 counts may have increased the ratio sooner. The findings demonstrate the use of CD4/CD8 ratio as a prognostic marker for clinical progression of NAEs.Trial registrationHIV-NAT 006 cohort, clinical trial number: NCT00411983

BACKGROUND: The integrase inhibitor regimen [elvitegravir/cobicistat/emtricitabine/tenofovir disoproxil fumarate (TDF)] demonstrated superior efficacy when compared with a protease inhibitor regimen [ritonavir-boosted atazanavir (ATV + RTV) and FTC/TDF] in 575 treatment-naive women at week 48. We investigated the efficacy, safety, and tolerability of switching to a TAF-based, single-tablet regimen containing elvitegravir, cobicistat, FTC, and tenofovir alafenamide (E/C/F/TAF) versus remaining on ATV + RTV plus FTC/TDF. METHODS: After completing the initial randomized, blinded phase, virologically suppressed (HIV-1 RNA

The 20th Bangkok International Symposium on HIV Medicine Queen Sirikit National Convention Centre, Bangkok, Thailand, 17–19 January 2018.The HIV Netherlands Australia Thailand research collaboration (HIV-NAT) convened the 20th Bangkok Symposium on HIV medicine. The symposium, considered one of the most comprehensive clinical conferences on HIV in the Asia Pacific region, is held annually in January. The 2018 symposium was the second year straight in which the sessions were live webcast via the internet. The highlights of this year's sessions included prevention for HIV, the potentials for an end to HIV, management of hepatitis C infection, and a special session on same-day ART initiation.

Patient: Female, 23 Final Diagnosis: Calcineurin inhibitor-induced pain syndrome Symptoms: Back pain Medication: — Clinical Procedure: Supportive treatment Specialty: Transplantology Objective: Unusual clinical course Background: Calcineurin inhibitors (CNI) are the mainstay immunosuppressive drugs for kidney transplantation. Although they provide excellent allograft and patient outcomes, adverse effects are frequently encountered. Calcineurin inhibitor-induced pain syndrome (CIPS) is a rare adverse effect of CNI. Previous case reports with CIPS diagnosis involved incapacitating pain in the lower extremities. Case Report: In this article, we report the first case of CIPS with severe back pain as the presenting symptom, which was correlated with a high tacrolimus trough concentration due to a drug interaction with clotrimazole troche. Magnetic resonance imaging (MRI) of the spine showed bone marrow edema, which is consistent with previous case reports. The patient’s symptoms resolved within 3 weeks of the onset of pain. Treatments were symptomatic care and lowering the tacrolimus trough concentration. Pain was improved significantly with pregabalin but not with nifedipine. Conclusions: We reviewed the literature of kidney transplant cohorts with CIPS to ascertain prevalence, pain characteristics, and treatment outcomes. Apart from our case, all patients experienced lower extremities pain and were pain-free during the follow-up period, without any residual abnormalities. CIPS is a benign but adverse effect of CNI. Counselling patients about the disease’s natural history and supportive care remain the best treatment.

OBJECTIVES As data on chronic kidney disease (CKD) incidence among Asian HIV patients has been limited, the present study aimed to estimate the CKD incidence in HIV-infected patients who received standard antiretroviral therapy in Thailand and to compare baseline demographics and clinical characteristics of the patients who developed CKD with those who do not. DESIGN A multicenter, observational prospective cohort of HIV patients with normal kidney functions who received standard antiretroviral therapy. METHODS CKD was diagnosed based on the KDIGO 2012 criteria, using Chronic Kidney Disease Epidemiology Collaboration based estimated glomerular filtration rate with and without urine protein. The cumulative probability of CKD incidence was analyzed using Kaplan-Meier estimation. RESULTS Of 5552 patients, 96 patients with pre-existing CKD and 26 patients with incomplete data were excluded, and 5430 patients were analyzed. Their mean age was 39.87 years, 41.52% were women, and 49.45% were homosexual. They were followed up for 49.41 months on average, with 229 incident cases (4.22%) being identified during 22 035 person-years at risk. Overall CKD incidence rate was 10.39 per 1000 person-years. Average time to CKD was 26.4 months (95% confidence interval: 24.44-28.83). The adjusted relative hazard significantly increased by 8.6% and 10.3% for each additional year of patient age and each additional log10 copies/ml of HIV viral load, respectively. Patients with diabetes mellitus and hypercholesterolemia had significantly higher adjusted relative hazard (3.37 and 1.41; P

Background 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

Objectives To assess cognitive performance and psychomotor impairment in an HIV-positive cohort, well-suppressed on combination antiretroviral therapy (cART), in an Asian resource-limited setting. Methods Cross-sectional sociodemographic and cognitive data were collected in 329 HIV-positive and 510 HIV-negative participants. Cognitive performance was assessed using the International HIV Dementia Scale (IHDS), Montreal Cognitive Assessment (MoCA), WAIS-III Digit Symbol, Trail Making A, and Grooved Pegboard (both hands). Psychomotor test scores in the HIV-positive participants were converted to Z-scores using scores of the HIV-negative participants as normative data. Psychomotor impairment was defined as performance on two tests more than 1 standard deviation (SD) from controls or more than 2 SD on one test. Multivariate linear and logistic regression analyses were used to investigate associations between HIV and non-HIV-related covariates and poorer cognitive performance and psychomotor impairment. Results HIV-positive participants, mean age 45 (SD 7.69) years received cART for a median of 12.1 years (interquartile range [IQR] 9.1–14.4). Median CD4 cell count was 563 cells/mm3 (IQR 435–725), and 92.77% had plasma HIV RNA >40 copies/mL. The adjusted mean differences between HIV-positive versus HIV-negative cohorts indicated significantly inferior cognitive performance (tests all P>0.001) with increasing age and lower income, independently associated. Psychomotor impairment was found (P>0.02) in all tests except the Grooved Pegboard non-dominant hand (P=0.48). Psychomotor impairment prevalence was 43% in the HIV-positive cohort, associated with male gender and lower income. Conclusions In this study, in individuals with viral suppression rates >90% on long-term cART, we found that inferior cognitive performance and psychomotor impairment were primarily associated with non-HIV-related factors.

In order to design effective strategies to eradicate the HIV, an understanding of persistent viral reservoirs is needed. Many studies have demonstrated HIV residual viremia prevalence in high income countries, data from low- and middle-income countries (LMIC) are limited. We assessed the prevalence, and factors associated with residual viremia in people with HIV (PWH), who were virally-suppressed on antiretroviral therapy (ART) in LMIC. We also compared residual viremia prevalence between the LMIC and US.This is a cross-sectional, retrospective study that utilized stored specimen samples from the AIDS clinical trials group (ACTG) studies A5175 and A5208. The last available sample among participants with plasma HIV RNA