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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.

Hepatitis C virus (HCV) prevalence is high among people living with HIV co-infected with HCV, people who inject drugs, men who have sex with men and inmates in correctional settings. The barriers to eliminate HCV among these key populations include diagnosis challenges, lack of awareness, discrimination and stigmatization. In addition, scaling up of HCV treatment has been a challenge in Asia–Pacific with the lack of national policies, targets and unavailability of appropriate direct-acting antivirals regimens. In order to achieve HCV micro elimination within these high-risk populations, novel strategies to improve the cascade of care from diagnosis to treatment with direct-acting antivirals, complemented by behavioral change interventions, harm reduction services for people who inject drugs, civil society led advocacy and policies from the government, will be necessary.

Coronavirus disease 2019 (COVID-19) was first detected in December 2019. In March 2020, the World Health Organization declared COVID-19 a pandemic. People with underlying medical conditions may be at greater risk of infection and experience complications from COVID-19. COVID-19 has the potential to affect People living with HIV (PLWH) in various ways, including be increased risk of COVID-19 acquisition and interruptions of HIV treatment and care. The purpose of this review article is to evaluate the impact of COVID-19 among PLWH. The contents focus on 4 topics: (1) the pathophysiology and host immune response of people infected with both SARS-CoV-2 and HIV, (2) present the clinical manifestations and treatment outcomes of persons with co-infection, (3) assess the impact of antiretroviral HIV drugs among PLWH infected with COVID-19 and (4) evaluate the impact of the COVID-19 pandemic on HIV services.

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.

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.

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.

Background In addition to traditional cardiovascular (CV) risk factors, antiretroviral therapy, lifestyle, and human immunodeficiency virus (HIV)-related factors may contribute to future CV events in persons with HIV (PWH). Methods Among participants in the global REPRIEVE randomized trial, we characterized demographics and HIV characteristics relative to ACC/AHA pooled cohort equations (PCE) for atherosclerotic CV disease predicted risk and CV health evaluated by Life’s Simple 7 (LS7; includes smoking, diet, physical activity, body mass index, blood pressure, total cholesterol, and glucose). Results Among 7382 REPRIEVE participants (31% women, 45% Black), the median PCE risk score was 4.5% (lower and upper quartiles Q1, Q3: 2.2, 7.2); 29% had a PCE score, Measures of cardiovascular (CV) risk and health are not closely related in persons with human immunodeficiency virus (HIV) in the REPRIEVE trial. Poor health scores among low-CV-risk persons with HIV suggest a critical role for lifestyle interventions regardless of CV risk prediction.

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.

There is limited evidence about the long-term changes in nutritional status among the elderly people living with human immunodeficiency virus (PLWH). We aimed to investigate the changes in nutritional status and related factors over 4 years in the elderly PLWH. The longitudinal study was conducted prospectively among 250 PLWH, 50 years of age and older, receiving antiretroviral therapy (ART). The Mini Nutritional Assessment (MNA) and Thai Depression Scale (TDS) to assess nutritional status and depression, respectively, were performed at the outpatient clinic both at baseline and 4-year follow-up. Majority were male (60.8%) with median age of 58 years. The median CD4 was 612.5 cells/mm

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.

Coinfection of HIV/HCV is a significant public health issue globally, as it increases the risk of liver cancer in co-infected individuals. The point-of-care testing (POCT) device for HIV/HCV DNA detection is promptly needed for diagnosis and monitoring of the disease progression. Here, the alternating-current electroluminescence (ACEL) technique is proposed as a sensitive POCT sensing platform for HIV/HCV cDNA detection. A conductance-based light emission modulated by the hybridization between a pyrrolidinyl PNA probe and the DNA target enabled the DNA detection in a label-free format. Enhanced electroluminescence was observed in the presence of the target DNA due to the increased proton conductivity. Under the optimal conditions, the linearity range from 1 nM to 1 μM was achieved for HIV and HCV cDNA with LODs of 1.86 pM (HIV cDNA) and 1.96 pM (HCV cDNA). The spiked HIV/HCV cDNA in healthy human serum was successfully detected, demonstrating the feasibility of the developed device for the detection of cDNA in real biological samples. Additionally, simultaneous HIV/HCV cDNA detection on a single ACEL device employing a 2x2-array detection zone design. The cross-reactivity with other viral DNA was shown to be minimal due to the high specificity of the PNA probes used. Finally, the negative and positive samples from the patient's serum were tested and the results were in 100% agreement with the commercial kit based-on real-time PCR method, thus illustrating the high sensitivity and specificity of the developed sensor.

Background Viral hepatitis is highly prevalent among people living with HIV (PLHIV) and can lead to chronic liver complications. Thailand started universal hepatitis B vaccination at birth in 1992. We explored prevalence rates of hepatitis B and C and associated factors among PLHIV from same-day antiretroviral therapy (SDART) service at the Thai Red Cross Anonymous Clinic, Bangkok, Thailand. Methods We collected baseline characteristics from PLHIV enrolled in the SDART service between July 2017 and November 2019. Multivariate logistic regression was carried out to determine factors associated with positive hepatitis B surface antigen (HBsAg) and hepatitis C antibody (anti-HCV). Results We included a total of 4,011 newly diagnosed PLHIV who had HBsAg or anti-HCV results at baseline. Included were 2,941 men who have sex with men (MSM; 73.3%), 851 general population (21.2%), 215 transgender women (TGW; 5.4%), and 4 transgender men (0.1%). Median age was 27 years. Overall seroprevalence of HBsAg and anti-HCV were 6.0% and 4.1%, respectively. Subgroup prevalence rates were 6.2% and 4.7% among MSM, 4.6% and 2.4% among general population, and 9.3% and 3.7% among TGW. Factors associated with HBsAg positivity were being MSM (adjusted odds ratio [aOR] 1.64, 95% confidence interval [CI] 1.13 to 2.40), being TGW (aOR 2.87, 95% CI 1.60 to 5.17), birth year before 1992 (aOR 2.32, 95% CI 1.69 to 3.16), CD4 count 3 (aOR 1.38, 95% CI 1.03, 1.86), and alanine aminotransferase ≥ 62.5 U/L (aOR 2.39, 95% CI 1.66 to 3.43). Factors associated with anti-HCV positivity were being MSM (aOR 2.11, 95% CI 1.26 to 3.55), age > 30 years (aOR 1.54, 95% CI 1.10 to 2.17), alanine aminotransferase ≥ 62.5 U/L (aOR 7.74, 95% CI 5.48 to 10.9), creatinine clearance

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 The combination of elbasvir and grazoprevir (EBR/GZR) has been approved for treating HCV infection. This study aimed to evaluate the efficacy of EBR/GZR in terms of sustained virological response (SVR) and improvement of liver fibrosis in Thai patients with HCV genotype-1 (GT1). The utility of serum HCV core antigen (HCVcAg) as an alternative to HCV RNA in assessing SVR was also investigated. Methods A total of 101 HCV GT1-infected patients (65 monoinfection and 36 HIV coinfection) who received EBR/GZR for 12–16 weeks were included. Liver stiffness (LS) and controlled attenuation parameter (CAP) were measured by transient elastography. Serum HCVcAg was measured in parallel with HCV RNA. Results The overall SVR12 and SVR24 rates in the cohort were 98.0% and 95.0%, respectively. SVR24 rates were consistently high (90.0% to 100%) across all subgroups of patients. A significant LS decline ≥30% was observed more frequently in cirrhotic than non-cirrhotic individuals who achieved SVR (63.3% versus 30.3%; P=0.003). The magnitude of LS decline following HCV eradication was comparable between HCV monoinfection and HCV–HIV coinfection. The reduction of CAP was also observed in responders who had significant steatosis at baseline. Compared with HCV RNA, HCVcAg testing displayed high sensitivity (100%) and specificity (99.0–100%) in determining SVR12 and SVR24. Conclusions This study confirms that EBR/GZR is effective for HCV GT1-infected Thai patients with or without HIV infection. HCV eradication is associated with LS and CAP improvement regardless of HIV status. HCVcAg testing could be a potential replacement for HCV RNA for assessing SVR in resource-limited settings.

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

Plasma viremia reoccurs in most HIV-infected individuals once antiretroviral therapy is interrupted, and interindividual differences in the kinetics of viral rebound have been associated with virological and immunological factors. Antibody features, including Fc functionality and Fc glycosylation, have been identified as sensitive surrogates for disease activity in multiple diseases., Plasma viremia reoccurs in most HIV-infected individuals once antiretroviral therapy (ART) is interrupted. The kinetics of viral rebound, specifically the time until plasma virus becomes detectable, differ quite substantially between individuals, and associations with virological and immunological factors have been suggested. Standard clinical measures, like CD4 T-cell counts and plasma HIV RNA levels, however, are poor predictive markers. Antibody features, including Fc functionality and Fc glycosylation have been identified as sensitive surrogates for disease activity in multiple diseases. Here, we analyzed HIV-specific antibody quantities and qualitative differences like antibody-mediated functions, Fc gamma receptor (FcγR) binding, and IgG Fc glycosylation as well as cytokine profiles and cellular HIV DNA and RNA levels in 23 ART-suppressed individuals prior to undergoing an analytical ART interruption (ATI). We found that antibodies with distinct functional properties and Fc glycan signatures separated individuals into early and delayed viral rebounders (≤4 weeks versus >4 weeks) and tracked with levels of inflammatory cytokines and transcriptional activity of the viral reservoir. Specifically, individuals with early viral rebound exhibited higher levels of total HIV-specific IgGs carrying inflammatory Fc glycans, while delayed rebounders showed an enrichment of highly functional antibodies. Overall, only four features, including enhanced antibody-mediated NK cell activation in delayed rebounders, were necessary to discriminate the groups. These data suggest that antibody features can be used as sensitive indicators of HIV disease activity and could be included in future ATI studies.

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.

BK virus (BKV) infection after kidney transplantation can cause BKV nephropathy (BKVAN) resulting in graft dysfunction and allograft loss. The treatment for BKVAN is reduction of the immunosuppressive load which increases the risk of kidney transplant rejection. There is no biomarker to monitor BKV activity besides BK viral load. The value of the Enzyme-Linked Immunosorbent Spot (ELISPOT) assay as a tool to monitor the recipient's anti-BKV immune response after transplantation was investigated systematically. Electronic databases, including MEDLINE, Scopus, and the Cochrane Central Register of Controlled Trials were searched for studies of ELISPOT evaluating the immune response against BKV. BKV status was categorized as "active BKV infection" and as "resolving BKV infection". Random-effects model meta-analysis was performed to determine the diagnostic performance of the ELISPOT assay, after stratifying patients into groups based on positive and negative ELISPOT results. One-hundred twenty-seven articles were identified of which nine were included. Patients with negative ELISPOT had an increased risk of having active BKV replication (odds ratio of 71.9 (95%-CI 31.0–167.1). Pooled sensitivity was 0.95 (95%-CI 0.89–0.98) and specificity was 0.88 (95%-CI 0.78–0.94). The standardized mean difference of the number of IFN-γ producing cells between patients with active BKV infection compared with patients who had resolving BKV infection was -2.09 (95%-CI -2.50, -1.68). The ELISPOT assay is a useful tool for BKV risk assessment and in combination with BKV load may support clinicians in guiding immunosuppressive therapy in patients with BKV replication.