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

Background Leptospirosis is one of the most important public-health zoonotic diseases in the tropics that can cause severe organ dysfunction and death. Currently there are insufficient data on long-term renal dysfunction in patients after leptospirosis infection. Methods A prospective multicentre cohort study was conducted at 15 hospitals in the Sisaket province of Thailand. Confirmed leptospirosis patients admitted from 1 December 2015 to 30 November 2018 were followed between 1 February 2020 and 31 October 2020 (median 4.1 years after hospital discharge). The primary outcome was a composite of major kidney adverse events (MAKEs) including all-cause mortality, dialysis and new-onset chronic kidney disease (CKD). Results Of the 217 confirmed leptospirosis cases enrolled, 32.7% were classified as having severe leptospirosis. Fifteen cases (6.9%) were deceased at the time of hospital admission. After a median follow-up time of 4.18 years, 30 patients had died and 33 patients developed CKD. Patients with severe leptospirosis had a significantly higher risk of MAKEs {adjusted hazard ratio 2.45 [95% confidence interval (CI) 1.44–4.18]}. Patients with intensive care unit admission, pulmonary haemorrhage and acute kidney injury also had a higher risk of MAKEs and all-cause mortality. Participants with severe leptospirosis in the follow-up cohort showed a higher risk of developing CKD compared with non-severe leptospirosis [adjusted odds ratio 3.22 (95% CI 1.04–9.96)], especially renal magnesium and phosphate wasting. Conclusion Leptospirosis patients, especially severe leptospirosis, are associated with long-term kidney sequelae. Our finding reflects the importance of long-term follow-up and the urgent need for specific interventions. [ABSTRACT FROM AUTHOR]

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

Background: Aging characteristics in people living with HIV (PLWH) are heterogeneous, and the identification of risk factors associated with aging-related comorbidities such as neurocognitive impairment (NCI) and frailty is important. We evaluated predictors of novel aging markers, phenotypic age (PhenoAge) and phenotypic age acceleration (PAA) and their association with comorbidities, frailty, and NCI. Methods: In a cohort of PLWH and age- and sex-matched HIV-negative controls, we calculated PhenoAge using chronological age and 9 biomarkers from complete blood counts, inflammatory, metabolic-, liver- and kidney-related parameters. PAA was calculated as the difference between chronological age and PhenoAge. Multivariate logistic regression models were used to identify the factors associated with higher (>median) PAA. Area under the receiver operating characteristics curve (AUROC) was used to assess model discrimination for frailty. Results: Among 333 PLWH and 102 HIV-negative controls (38% female), the median phenotypic age (49.4 vs. 48.5 years, p = 0.54) and PAA (− 6.7 vs. -7.5, p = 0.24) was slightly higher and PAA slightly less in PLWH although this did not reach statistical significance. In multivariate analysis, male sex (adjusted odds ratio = 1.68 [95%CI = 1.03–2.73]), current smoking (2.74 [1.30–5.79]), diabetes mellitus (2.97 [1.48–5.99]), hypertension (1.67 [1.02–2.72]), frailty (3.82 [1.33–10.93]), and higher IL-6 levels (1.09 [1.04–1.15]), but not HIV status and NCI, were independently associated with higher PAA. PhenoAge marker discriminated frailty better than chronological age alone (AUROC: 0.75 [0.66–0.85] vs. 0.65 [0.55–0.77], p = 0.04). In the analysis restricted to PLWH, PhenoAge alone predicted frailty better than chronological age alone (AUROC: 0.7412 vs. 0.6499, P = 0.09) and VACS index (AUROC: 0.7412 vs. 0.6811, P = 0.34) despite not statistically significant. Conclusions: While PLWH did not appear to have accelerated aging in our cohort, the phenotypic aging marker was significantly associated with systemic inflammation, frailty, and cardiovascular disease risk factors. This simple aging marker could be useful to identify high-risk PLWH within a similar chronological age group. [ABSTRACT FROM AUTHOR]

Background: We compared weight changes in virally suppressed people living with HIV (PLWH) switching to integrase strand transfer inhibitors (INSTIs) with those remaining on an INSTI or non-INSTI regimen.Methods: PLWH aged ≥18 years with weight measurements available at baseline between 2001 and 2020 were included. Viral suppression was defined as having had a viral load <400 copies/mL for 6 months. Baseline was defined as the time of switching from a non-INSTI to an INSTI regimen whilst virally suppressed (switch group) or the time that viral suppression was achieved (remain groups). Generalized estimating equations adjusted for age, sex and baseline weight were used to model weight changes 6, 12, 18 and 24 months after baseline.Results: A total of 1673 PLWH contributed 1952 episodes of viral suppression-143 (7.3%) episodes were among PLWH who had switched from a non-INSTI to an INSTI, 102 (5.2%) episodes were among PLWH who remained on an INSTI and 1707 (87.4%) episodes were among PLWH who remained on a non-INSTI. PLWH in the switch group had significantly greater weight gain than those in the remain groups at 6, 12 and 18 months after achieving viral suppression. By 24 months, weight change on all regimens started to converge. Tenofovir alafenamide use was not significantly associated with weight gain in adjusted models.Conclusions: Our findings suggest that the mechanisms of weight gain due to INSTI use go beyond their superior efficacy over other antiretrovirals in controlling HIV or the effect of the 'return-to-health' phenomenon. Further research is needed to understand the mechanisms of such weight gain. [ABSTRACT FROM AUTHOR]

Background: Viral hepatitis is highly prevalent among people with HIV (PWH) and can lead to chronic liver complications. Thailand started universal hepatitis B vaccination at birth in 1992 and achieved over 95% coverage in 1999. We explored the prevalence of hepatitis B and C viral infections and the associated factors among PWH from same-day antiretroviral therapy (SDART) service at the Thai Red Cross Anonymous Clinic, Bangkok, Thailand.Methods: We collected baseline characteristics from PWH enrolled in the SDART service between July 2017 and November 2019. Multivariable logistic regression was performed to determine factors associated with positive hepatitis B surface antigen (HBsAg) and hepatitis C antibody (anti-HCV).Results: A total of 4011 newly diagnosed PWH who had HBsAg or anti-HCV results at baseline: 2941 men who have sex with men (MSM; 73.3%), 851 heterosexuals (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 were 6.2 and 4.7% among MSM, 4.6 and 2.4% among heterosexuals, and 9.3 and 3.7% among TGW, respectively. Factors associated with HBsAg positivity were being MSM, TGW, born before 1992, CD4 count < 200 cells/mm3, and alanine aminotransferase ≥ 62.5 U/L. Factors associated with anti-HCV positivity were being MSM, age > 30 years, alanine aminotransferase ≥ 62.5 U/L, creatinine clearance < 60 ml/min, and syphilis infection.Conclusions: Around 5-10% of newly diagnosed PWH in Bangkok had hepatitis B viral infection after 25 years of universal vaccination. Anti-HCV positivity was found in 4-5% of PWH who were MSM and TGW. As World Health Organization and Thailand national guidelines already support routine screening of hepatitis B and C viral infections in PWH and populations at increased risk of HIV including MSM and TGW, healthcare providers should reinforce this strategy and provide linkage to appropriate prevention and treatment interventions. Catch-up hepatitis B vaccination should be made available under national health coverage. [ABSTRACT FROM AUTHOR]

Background: People 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. Methods: Our 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%. Results: A 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. Conclusions: Reducing 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. [ABSTRACT FROM AUTHOR]

Background: Prisons are considered as major reservoirs for tuberculosis. Preventive therapy for latent TB infection (LTBI) is an adjunctive strategy to control TB. However, LTBI data in Thai prisoners is limited. This study assessed the prevalence of LTBI and feasibility of isoniazid preventive therapy (IPT).Methods: A cross-sectional study was conducted among prisoners in Klong Prem Central Prison, Bangkok. Participants were screened for active TB by questionnaire and chest X-ray. LTBI was evaluated by Tuberculin skin test (TST) and QuantiFERON-TB Gold Plus (QFTP) among subgroup. Participants with positive TST or QFTP were considered to have LTBI. Participants with LTBI were offered IPT.Results: From August 2018-November 2019, 1002 participants were analyzed. All participants were male with a median age of 38 (IQR 32-50) years. LTBI identified by either TST/QFTP was present in 466 (46.5%) participants. TST was positive in 359 (36%) participants. In the subgroup of 294 participants who had both TST and QFTP results, 181/294 (61.6%) tested positive by QFTP. Agreement between TST and QFTP was 55.1% (Kappa = 0.17). The risk factors associated with LTBI were previous incarceration (aOR 1.53, 95%CI, 1.16-2.01, p = 0.002), history of prior active TB (aOR 3.02, 95%CI, 1.74-5.24, p < 0.001) and duration of incarceration ≥10 years (aOR 1.86, 95%CI, 1.24-2.79, p = 0.003). Majority of LTBI participants (82%) agreed to take IPT. Three hundred and 56 (93%) participants completed treatment whereas 27 (7%) participants discontinued IPT due to the side effects of INH.Conclusion: This is the first study to evaluate the prevalence of LTBI and feasibility of IPT among Thai prisoners. LTBI prevalence in male prisoners in Thailand is high. LTBI screening and treatment should be implemented together with other preventive components. [ABSTRACT FROM AUTHOR]

BIT225 is a first-in-class inhibitor of human immunodeficiency virus (HIV) type 1 Vpu. A phase II trial enrolled 36 HIV-1-infected, treatment-naive participants in Thailand to receive standard-of-care antiretroviral therapy (ART), tenofovir disoproxil fumarate/emtricitabine/efavirenz (Atripla), with 100 or 200 mg of BIT225 or placebo (daily) for 12 weeks. Combined treatment with BIT225 and ART was found to be generally safe and well tolerated, with antiviral efficacy comparable to that of ART alone. The secondary end point-soluble CD163, a marker of monocyte/macrophage inflammation-was noted to be significantly decreased in the BIT225 arm. Plasma-derived activated CD4+ and CD8+ T cells, natural killer cells, and interleukin 21 were increased in those treated with BIT225. These findings are consistent with inhibition of the known effects of HIV Vpu and may reflect clinically important modulation of inflammatory and immune function. Further clinical study is planned to both confirm and extend these important findings in treatment-naive, and treatment-experienced individuals. Clinical Trials Registration. Australian New Zealand Clinical Trials Registry (Universal Trial Number U1111-1191-2194). [ABSTRACT FROM AUTHOR]

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

There are limited studies regarding bone health among people living with HIV (PLHIV) in Asia. We compared bone mineral density (BMD), serum 25-hydroxyvitamin D (25(OH)D) status and bone turnover markers (serum procollagen type1 N-terminal propeptide (P1NP), osteocalcin (OC) and C-terminal cross-linking telopeptide of type1 collagen) among 302 antiretroviral therapy (ART) naive PLHIV compared to 269 HIV-uninfected controls from Thailand. People aged ≥30 years, with and without HIV infection (free of diabetes, hypertension, and active opportunistic infection) were enrolled. BMD at the lumbar spine, total hip, and femoral neck were measured using Hologic DXA at baseline and at 5 years. We analyzed BMD, serum 25(OH)D levels, and bone turnover markers at the patients' baseline visit. PLHIV were 1.5 years younger and had lower BMI. PLHIV had higher mean serum 25(OH)D level and similar BMD to the controls. Interestingly, PLHIV had significantly lower bone formation (serum P1NP and OC), particularly those with low CD4 count. Only a few participants had low bone mass. ARV naïve middle-aged PLHIV did not have lower BMD or lower vitamin D levels compared to the controls. However, PLHIV had lower bone formation markers, particularly those with low CD4 count. This finding supports the benefit of early ART. [ABSTRACT FROM AUTHOR]

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

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. [ABSTRACT FROM AUTHOR]

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 (<2%), and only MoCA/TDS/MNA/HSI were analyzed. A VACSI < 17 produces 85% sensitivity (Se) and 30% specificity (Sp) (area under the ROC curve [AUC] = 63, 95%CI 58–69) and G-8 > 15.5 produces 90%Se and 33%Sp (AUC = 74, 95%CI 69–79) in identifying patients with <2 impaired domains. A G-8 > 13.5 produces 91%Se and 77%Sp (AUC = 89, 95%CI 86–92) in ruling out abnormal nutrition. Patients with VACSI < 17 and G-8 > 15.5 may forego CGA due to low likelihood of abnormal cognition, mood, nutrition, or symptom burden. [ABSTRACT FROM AUTHOR]

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 < 2400 mL and those with urine output ≥ 2400 mL (35.3 ± 6.6 and 47.4 ± 15.2, respectively; P = 0.002), and between patients with 24-h measured CrCl < 25 mL/min and those with CrCl ≥ 25 mL/min (38.0 (29.0, 42.2) and 49.2 ± 14.0, respectively; P = 0.017). Proportions of overall biopsy proven acute rejection among patients with mycophenolic acid AUC of < 45 and ≥ 45 mg*h/L were comparable (20.0% and 23.5%, respectively; P = 1.000). Conclusions After the starting dosage of 1.5 g/d mycophenolate mofetil, the mean mycophenolic acid AUC on day 3 post-kidney transplantation is comparable with the target of 45 mg*h/L. Severely reduced renal function significantly influences mycophenolic acid exposure. [ABSTRACT FROM AUTHOR]

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Background: Abacavir and rilpivirine are alternative antiretroviral drugs for treatment-naïve HIV-infected patients. However, both drugs are only recommended for the patients who have pre-treatment HIV RNA <100,000 copies/mL. In resource-limited settings, pre-treatment HIV RNA is not routinely performed and not widely available. The aims of this study are to determine factors associated with pre-treatment HIV RNA <100,000 copies/mL and to construct a model to predict this outcome. Methods: HIV-infected adults enrolled in the TREAT Asia HIV Observational Database were eligible if they had an HIV RNA measurement documented at the time of ART initiation. The dataset was randomly split into a derivation data set (75% of patients) and a validation data set (25%). Factors associated with pre-treatment HIV RNA <100,000 copies/mL were evaluated by logistic regression adjusted for study site. A prediction model and prediction scores were created. Results: A total of 2592 patients were enrolled for the analysis. Median [interquartile range (IQR)] age was 35.8 (29.9-42.5) years; CD4 count was 147 (50-248) cells/mm³; and pre-treatment HIV RNA was 100,000 (34,045-301,075) copies/ mL. Factors associated with pre-treatment HIV RNA <100,000 copies/mL were age <30 years [OR 1.40 vs. 41-50 years; 95% confidence interval (CI) 1.10-1.80, p = 0.01], body mass index >30 kg/m² (OR 2.4 vs. <18.5 kg/m²; 95% CI 1.1-5.1, p = 0.02), anemia (OR 1.70; 95% CI 1.40-2.10, p < 0.01), CD4 count ≥350 cells/mm³ (OR 3.9 vs. <100 cells/mm³; 95% CI 2.0-4.1, p < 0.01), total lymphocyte count >2000 cells/mm³ (OR 1.7 vs. <1000 cells/mm³; 95% CI 1.3-2.3, p < 0.01), and no prior AIDS-defining illness (OR 1.8; 95% CI 1.5-2.3, p < 0.01). Receiver-operator characteristic (ROC) analysis yielded area under the curve of 0.70 (95% CI 0.67-0.72) among derivation patients and 0.69 (95% CI 0.65-0.74) among validation patients. A cut off score >25 yielded the sensitivity of 46.7%, specificity of 79.1%, positive predictive value of 67.7%, and negative predictive value of 61.2% for prediction of pre-treatment HIV RNA <100,000 copies/mL among derivation patients. Conclusion: A model prediction for pre-treatment HIV RNA <100,000 copies/mL produced an area under the ROC curve of 0.70. A larger sample size for prediction model development as well as for model validation is warranted. [ABSTRACT FROM AUTHOR]

HIV/AIDS and anxiety/depression are interlinked. HIV-infected patients suffering from depression may be at risk for poor adherence which may contribute to HIV disease progression. Additionally, an HIV diagnosis and/or using certain antiretroviral agents may trigger symptoms of anxiety/depression. The objective of the study was to assess the prevalence and factors associated with anxiety and depression in HIV-infected patients from the Thai National HIV Treatment Program. This cross-sectional study was performed from January 2012 to December 2012 in HIV-infected out-patients, aged ≥18 years, from three HIV referral centers. Symptoms of anxiety and depression were measured using the Thai-validated Hospital Anxiety and Depression Scale (HADS). A score of ≥11 was defined as having anxiety and depression. Associated factors were assessed by multivariate logistic regression. Totally 2023 (56% males) patients were enrolled. All patients received antiretroviral therapy (ART) for a mean duration of 7.7 years. Median CD4 was 495 cells/mm3. Ninety-five percent had HIV-RNA < 50 copies/ml. Thirty-three percent were currently on efavirenz (EFV)-based ART. The prevalence of anxiety and depression were 4.8% and 3.1%, respectively. About 1.3% had both anxiety and depression. In multivariate logistic models, the female sex [OR = 1.6(95%CI 1.1–2.3),p = .01], having adherence <90% [OR = 2.2(95%CI 1.5–3.4),p < .001], fair/poor quality of life (QOL) [OR = 7.2 (95%CI 3.6–14.2),p < .001] and EFV exposure [OR = 1.6(95%CI 1.1–2.3),p = .01], were independently associated with having anxiety or depression. Our findings demonstrated that prevalence of depression and anxiety was low amongst virally suppressed, long-term antiretroviral-treated HIV-infected individuals. Some key characteristics such as the female sex, poor adherence, poor/fair QOL and EFV exposure are associated with anxiety and depression. These factors can be used to distinguish who would need a more in-depth evaluation for these psychiatric disorders. [ABSTRACT FROM PUBLISHER]

Although HIV prevalence remains high among Bangkok's MSM early HIV testing as an entry point to ART has not been successfully implemented among in this population. Men who present late for initial HIV testing are a particular concern in the context of the Bangkok HIV epidemic, in that if long-term positives have had condomless sex during the time that they remained untreated they are likely to have been efficient transmitters of infection, to say nothing of the implications for their own health. A sequential sample of MSM who tested HIV positive, and CD4 counts, was taken at the Thai Red Cross Anonymous Clinic and two drop-in centers in Bangkok. Inclusion criteria were MSM aged >18 years, having not tested HIV positive earlier, who reported ≥1 of the following in the previous 6 months: condomless sex with a male, being a sex worker, or having a sexual transmitted infection (STI) diagnosis. Analysis was conducted by distinguishing between three groups of CD4 counts: <200, 200-500, >500 cells/μ to identify the social and behavioral characteristics of the men who presented late for HIV testing. Median CD4 was 325 cells/μ(n = 95). MSM with initial CD4< 200 cells/μ were significantly more likely to report problematic alcohol use. They were also more likely to report receptive anal sex and more likely to be engaged in sex work. MSM with CD4< 200 cells/μ were less likely to report recent HIV testing. Main barriers to HIV testing included being afraid of finding out that they were HIV positive and concerns about efficacy and side effects of HIV treatment. HIV stigma and concerns about treatment are still widespread and are potential barriers to HIV care among MSM in Bangkok. These barriers may work to keep men from finding out their positive HIV status in a timely manner. Thai MSM need to be made aware of the current availability of friendly HIV testing and ART services, and public health programs need to work to change their perceptions regarding ART itself. These same types of strategies might also work to destigmatize HIV and MSM within Thai society as a whole. [ABSTRACT FROM AUTHOR]

Objectives: Ensuring that medicines meet quality standards is mandatory for ensuring safety and efficacy. There have been occasional reports of substandard generic medicines, especially in resource-limiting settings where policies to control quality may be less rigorous. As HIV treatment in Thailand depends mostly on affordable generic antiretrovirals (ARV), we performed quality assurance testing of several generic ARV available from different sources in Thailand and a source from Vietnam. Methods: We sampled Tenofovir 300mg, Efavirenz 600mg and Lopinavir/ritonavir 200/50mg from 10 primary hospitals randomly selected from those participating in the National AIDS Program, 2 non-government organization ARV clinics, and 3 private drug stores. Quality of ARV was analyzed by blinded investigators at the Faculty of Pharmaceutical Science, Chulalongkorn University. The analysis included an identification test for drug molecules, a chemical composition assay to quantitate the active ingredients, a uniformity of mass test and a dissolution test to assess in-vitro drug release. Comparisons were made against the standards described in the WHO international pharmacopeia. Results: A total of 42 batches of ARV from 15 sources were sampled from January–March 2015. Among those generics, 23, 17, 1, and 1 were Thai-made, Indian-made, Vietnamese-made and Chinese-made, respectively. All sampled products, regardless of manufacturers or sources, met the International Pharmacopeia standards for composition assay, mass uniformity and dissolution. Although local regulations restrict ARV supply to hospitals and clinics, samples of ARV could be bought from private drug stores even without formal prescription. Conclusion: Sampled generic ARVs distributed within Thailand and 1 Vietnamese pharmacy showed consistent quality. However some products were illegally supplied without prescription, highlighting the importance of dispensing ARV for treatment or prevention in facilities where continuity along the HIV treatment and care cascade is available. [ABSTRACT FROM AUTHOR]

What is known and objective Tacrolimus, the most widely used calcineurin inhibitor in kidney transplantation, has a narrow therapeutic window with high interindividual variability in its pharmacokinetics. Clinically feasible models that combine important factors may help guide individual tacrolimus dosage adjustment in kidney transplant patients. The purpose of this study was to develop a population pharmacokinetic model and investigate the influence of clinical factors on the pharmacokinetics of tacrolimus in adult Thai kidney transplant patients from routine data monitoring. Methods A total of 1183 whole blood concentrations from 96 patients were characterized using nonlinear mixed-effects modelling. Clinical factors tested for influence on pharmacokinetic parameters were weight, haemoglobin, duration of tacrolimus therapy, prednisolone dose, serum albumin and estimated glomerular filtration rate. Results and discussion A one-compartment model with first-order absorption best described the data. The population estimate of tacrolimus apparent clearance ( CL/ F) and apparent volume of distribution ( V/ F) in the final population model was 21·5 L/h (95% CI; 18·38, 24·34) and 333 L (95% CI; 222·66, 484·35), respectively. CL/ F increased with decreasing haemoglobin levels and decreased with increasing duration of tacrolimus therapy (both P < 0·001). The population pharmacokinetic equation that predicted CL/ F of tacrolimus was CL/ F = 21·5 × exp(−0·05 ( HB − 11·8)) × ( DOT/125)−0·06, where CL/ F was tacrolimus apparent oral clearance (L/h), HB was haemoglobin levels (g/dL), and DOT was duration of tacrolimus therapy (days). No covariates significantly influenced V/ F. What is new and conclusion The first population pharmacokinetic model of tacrolimus in Thai adult kidney transplant patients was developed and validated. Haemoglobin and duration of tacrolimus therapy could partly explain the interindividual variability in the apparent clearance of tacrolimus. This manuscript also provides a summary review of previously reported population pharmacokinetic models of twice daily tacrolimus in adult kidney transplant recipients. [ABSTRACT FROM AUTHOR]

The objective of this study was to characterize HIV-serodiscordant heterosexual couples and to evaluate acceptance for HIV testing and HIV prevalence in nonindex partners. We conducted a cross-sectional study with quantitative and qualitative components. Two cohorts of 1767 HIV-positive people were screened to identify heterosexual HIV-serodiscordant couples. HIV-positive partners (index) were administered a questionnaire; CD4, viral load (VL), and antiretroviral therapy (ART) history were gathered from clinical records. HIV-negative/unknown status partners (nonindex) were invited for a similar questionnaire and HIV testing. In-depth interviews with three HIV-serodiscordant couples were conducted. Two hundred and ninety-seven index partners agreed to enroll in this study. The median duration of the relationship was 10 years, and 81% were sexually active. All but two index partners were on ART, and 98% had VL < 1000 copies/mL. Only 111 (37%) nonindex partners came for HIV testing, and all of them tested HIV-negative. In addition, only 41% of nonindex partners had HIV testing in the last one year. The main reasons for the nonindex partners not to come for HIV testing were “no interest” (n= 117, 63%) and “nondisclosure of HIV status” (n= 46, 25%). The latter was substantiated and explained by the qualitative outcome of this study, suggesting relation to stigma against HIV-positive people. Our results support the WHO recommendation for starting ART for treatment and prevention in HIV-serodiscordant couples at any CD4 count. Furthermore, we recommend the dissemination of data showing that no HIV transmission in heterosexual couples through sex practice has been observed provided VL is suppressed. This could be a powerful tool for effective fight against stigma and self-stigma in people living with HIV. [ABSTRACT FROM AUTHOR]

Background: Thailand has experienced a longstanding epidemic of HIV among people who inject drugs (PWID). However, antiretroviral treatment (ART) coverage among HIV-positive PWID has historically remained low. While ongoing drug law enforcement involving periodic police crackdowns is known to increase the risk of HIV transmission among Thai PWID, the impact of such drug policy approaches on the ART uptake has been understudied. Therefore, we sought to identify factors associated with not receiving ART among HIV-positive PWID in Bangkok, Thailand, with a focus on factors pertaining to drug law enforcement. Methods: Data were collected from a community-recruited sample of HIV-positive PWID in Bangkok who participated in the Mitsampan Community Research Project between June 2009 and October 2011. We identified factors associated with not receiving ART at the time of interview using multivariate logistic regression. Results: In total, 128 HIV-positive PWID participated in this study, with 58 (45.3%) reporting not receiving ART at the time of interview. In multivariate analyses, completing less than secondary education (adjusted odds ratio [AOR]: 3.32 ; 95% confidence interval [CI]: 1.48 - 7.45), daily midazolam injection (AOR: 3.22, 95% CI: 1.45 - 7.15) and exposure to compulsory drug detention (AOR: 3.36, 95% CI: 1.01 - 11.21) were independently and positively associated with not receiving ART. Accessing peer-based healthcare information or support services was independently and positively associated with receiving ART (AOR: 0.21, 95% CI: 0.05 - 0.84). Conclusions: Approximately half of our study group of HIV-positive PWID reported not receiving ART at the time of interview. Daily midazolam injectors, those with lower education attainment, and individuals who had been in compulsory drug detention were more likely to be non-recipients of ART whereas those who accessed peer-based healthcare-related services were more likely to receive ART. These findings suggest a potentially adverse impact of compulsory drug detention and highlight the need to expand interventions to facilitate access to ART among HIV-positive PWID in this setting. [ABSTRACT FROM AUTHOR]

New evidence has emerged regarding when to commence antiretroviral therapy (ART), optimal treatment regimens, management of HIV co-infection with opportunistic infections, and management of ART failure. The 2014 guidelines were developed by the collaborations of the Department of Disease Control, Ministry of Public Health (MOPH) and the Thai AIDS Society (TAS). One of the major changes in the guidelines included recommending to initiating ART irrespective of CD4 cell count. However, it is with an emphasis that commencing HAART at CD4 cell count above 500 cell/mm³ is for public health, in term of preventing HIV transmission and personal benefit. In tuberculosis co-infected patients with CD4 cell counts <50 cells/mm³ or with CD4 cell counts >50 cells/mm³ who have severe clinical disease, ART should be initiated within 2 weeks of starting tuberculosis treatment. The preferred initial ART regimen in treatment naïve patients is efavirenz combined with tenofovir and emtricitabine or lamivudine. Plasma HIV viral load assessment should be done twice a year until achieving undetectable results; and will then be monitored once a year. CD4 cell count should be monitored every 6 months until CD4 cell count ≥350 cells/mm³ and with plasma HIV viral load <50 copies/mL; then it should be monitored once a year afterward. HIV drug resistance genotypic test is indicated when plasma HIV viral load >1,000 copies/mL while on ART. Ritonavir-boosted lopinavir or atazanavir in combination with optimized two nucleoside-analogue reverse transcriptase inhibitors is recommended after initial ART regimen failure. Long-term ART-related safety monitoring has also been included in the guidelines. [ABSTRACT FROM AUTHOR]

Objective. The aim of this study was to assess the value of four drug regimens for newly diagnosed severe LN from a societal perspective.Methods. A model-based cost–utility analysis was devised to measure lifetime costs and health outcomes. Current treatment options consisting of different combinations of i.v. CYC, AZA and MMF were compared with a baseline regimen of i.v. CYC in both the induction and maintenance phases. Resource use and costs were derived from medical records reviews and databases. Event rates were elicited from randomized controlled trials. Relative treatment effects were obtained from meta-analyses. Health utilities were obtained from a real cohort of patients to estimate the outcome of quality-adjusted life years.Results. It was found that a treatment regimen that combined i.v. CYC in the induction phase with AZA in the maintenance phase was cost saving compared with the baseline regimen. Treatment with i.v. CYC in the induction phase and MMF in the maintenance phase and treatment with MMF in the induction phase and a reduced dose of the same in the maintenance phase turned out to be a negatively dominated regimen.Conclusion. In the Thai context, the combination of i.v. CYC for the induction phase followed by AZA for the maintenance phase should be considered as the first-line therapy for newly diagnosed severe LN, as it seems to be the most cost-saving regimen. [ABSTRACT FROM PUBLISHER]

Background: Antiretroviral therapy (ART) is known to reduce tuberculosis (TB) incidence among people living with HIV (PLWH). However, studies describing the impact of long-term ART and CD4 count recovery on TB incidence remain scarce due to limited follow up in previous studies. We evaluated TB incidence in a long-term cohort of PLWH on ART in Thailand.Methods: We conducted an analysis of PLWH aged ≥ 18 years who started ART between 1996 and December 2020. Participants were followed up every 6 months for routine HIV care. TB risk factors, body mass index (BMI), physical examination and full differential blood counts were evaluated at each clinic visit, and CD4 cell counts and HIV RNA every 12 months. Participants diagnosed with TB > 3 months after starting ART were classified as incident cases. Time to event models with death as a competing risk, were used to derive the TB cumulative incidence function (CIF) after ART initiation, and assess time-updated factors associated with incident TB using a six month lag.Results: A total of 2,636 PLWH contributing 24,229 person years (PY) of follow-up on ART were analysed. Median age was 32.0 (IQR 27.4-37.6) years; 67.5% were male. Median CD4 cell count at ART initiation was 264 (IQR 167-379) cells/mm3 and median follow-up duration was 7.6 (IQR 1.9-15.7) years. During follow-up, 113 PLWH developed TB. The probability of incident TB was 0.7%, 1.7%, 3.3% and 4.3%, at 1, 2, 5 and 7 years after ART initiation, respectively. TB CIF was highest among participants with CD4 < 50 cells/mm3. The overall crude incidence of TB was 4.66 (95% CI 3.87-5.60) per 1000 PY. Low CD4 count, BMI < 18 kg/m2, and substance use in the previous six months were significantly associated with incident TB. Incidence declined with time on suppressive ART, but remained higher than the Thai general population 7 years after ART initiation (2.2 vs 1.5/1000 PY, respectively).Conclusion: Despite a marked reduction in TB incidence following ART, ongoing TB risk remains high among PLWH, despite long-term suppressive ART. Those with low CD4 cell counts, who are underweight, or currently having substance abuse should be carefully monitored. [ABSTRACT FROM AUTHOR]

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

Background: Increasing rates of non-AIDS defining illnesses, and in particular liver diseases, have been found after the initiation of highly active antiretroviral therapy. However, there is little evidence concerning the risk factors for and clinical characteristics of liver disease in antiretroviral (ARV)-treated HIV infection, in the absence of hepatitis B or C viral co-infection. Methods: A nested case-control study of HIV infected volunteers, matched by starting date of anti-retroviral treatment, was conducted in a Thai cohort studied from Nov 2002--July 2012. Cases were defined as those subjects with an elevated alanine aminotransferase (ALT ≥ 40 IU/L) at two consecutive visits six months apart, while controls were defined as individuals who never demonstrated two consecutive elevated ALT results and had a normal ALT result (< 40 IU/L) at their last visit. Both groups had normal ALT levels prior to ARV initiation. Clinical demographics and risk factors for chronic hepatitis including HIV-related illness, ARV treatment and metabolic diseases were collected and analyzed. Conditional logistic regression was used to determine risk factors for chronic hepatitis in HIV infection. Results: A total of 124 matched pairs with HIV infection were followed over 3,195 person-years. The mean age (±SD) was 33.0 ± 7.3 years, with 41.1% of subjects being male. The incidence of chronic hepatitis was 5.4 per 100 person-years. The median time from initiation of ARV to chronic hepatitis was 1.3 years (IQR, 0.5-3.5). From univariate analysis; male sex, plasma HIV-1 RNA level > 5 log 10 copies/ml, metabolic syndrome at baseline visit, high BMI > 23 kg/m2, abnormal HDL cholesterol at time of ALT elevation and treatment experience with NNRTI plus boosted PI were selected (p value < 0.2) to the final model of multivariate analysis. Male sex had 3.1 times greater risk of chronic hepatitis than the females by multivariate analysis (adjusted OR, 95% CI: 3.1, 1.5-6.3, p =0.002). High BMI 2 23 kg/m2 was also associated with 2.4 times greater risk of chronic hepatitis (adjusted OR, 95% CI: 2.4, 1.2-4.8, p = 0.01). Conclusions: Chronic hepatitis in ARV-treated HIV-infected patients is common and may lead to a major health care problem. Male sex and high BMI 2 23 kg/m2 carry higher risks for developing chronic hepatitis in this study. Therefore, these patients should be closely monitored for long-term hepatotoxicity. [ABSTRACT FROM AUTHOR]

In settings where medications and viral load (VL) monitoring are limited by cost, clinicians need reliable ways to assess patient adherence to therapy. We assessed sensitivity and specificity of two self-reported adherence tools (a visual analogue scale [VAS] and the CASE [Center for Adherence Support Evaluation] adherence index), against a standard of detectable VL, with 288 patients from three sites in Thailand. We also assessed predictors of non-adherence. The sensitivity and specificity of the VAS <95% and CASE adherence index ≤11 against a VL >50 copies/mL were 26% and 90%, 19% and 95%, respectively. Against a VL ≥1000 copies/mL sensitivities increased to 55% and 36%, respectively, and specificities were unchanged. Attending a clinic not staffed by HIV specialists (odds ratio [OR] 3.14; 95% confidence interval [Cl] 1.19-8.34) and being educated to primary school level or less (OR 2.24; 95% Cl 1.01 -4.94) were associated with self-reported adherence <95% on the VAS in multivariate analysis. Adherence assessed by the VAS was a more accurate predictor of detectable VL. Policy-makers in resource-limited settings should ensure that treatment centres are staffed with well-trained personnel aware of the importance of good patient adherence. [ABSTRACT FROM AUTHOR]

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

Background: In Thailand, dialysate endotoxin contamination levels vary from less than 0.001 to 2.0 EU/ml. This difference has prompted an investigation on the production of proinflammatory cytokines and counter-inflammatory mediators of peripheral blood mononuclear cells (PBMCs) after high-flux dialysis. Methods: Patients from four hemodialysis (HD) centers who met the inclusion/exclusion criteria were enrolled into the study. PBMCs were isolated by Ficoll density gradient centrifugation and cultured. Supernatants were tested for interleukin 6 (IL-6), IL-1β and IL-1 receptor antagonist (IL-1Ra) concentration by ELISA. Results: HD centers 1, 2, 3 and 4 had mean dialysate endotoxin contamination levels of 0.001, 0.026, 0.558 and 1.960 EU/ml, respectively. HD center 4 had the highest levels of IL-6 (1,052.3 ± 240.7 pg/106 PBMCs), IL-1β (1,297.1 ± 334.6 pg/106 PBMCs) and IL-1Ra (2,713.4 ± 1,255.3 pg/106 PBMCs). There were no significant differences in cytokine production between HD centers 1 and 2. Conclusion: Our study showed that ultrapure dialysate can minimize the risk of stimulating inflammatory cells. Ultrapure dialysate may prevent or delay endotoxin exposure-related complications. Copyright © 2011 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Abstract: Introduction: Kidney transplantation is the best treatment for end-stage renal disease patients. Delayed graft function (DGF) remains one of the major problems after cadaveric kidney transplantation. This study has reported the risk factors and outcomes of DGF using data from Thai Transplant Registry Database. Methods: The data of all cadaveric kidney transplantations (CD-KT) were retrieved from the database. DGF was defined as a failure to decrease the serum creatinine within 72 hours or a requirement for dialysis within the first week after transplantation. We performed logistic regression analysis to correlate donor features (age, sex, cardio-pulmonary resuscitation (CPR), brain death from a cerebrovascular accident (CVA), best and last serum creatinine) with recipient demographics (age, sex) and clinical outcomes cold ischemic time [CIT] and DGF. Results: We analyzed 756 CD-KT including 320 (42%) patients experiencing DGF. Upon multivariate analysis, factors significantly correlated with DGF were CIT (P < .001), donor last serum creatinine (P < .001), interleukin 2 monoclonal antibody induction (P = .004), donor age (P = .017), donor CVA (P = .012), and prior peritoneal dialysis (PD) (P = .012). There was no significant correlation between DGF and donor height, weight, sex, CPR, brain death from CVA, best serum creatinine, recipient age, or sex in multivariate analysis. Graft survivals at 1 and 5 years after transplantation were significantly lower among the DGF group namely, 91.0% vs. 95.2% and 78.7% vs. 86.0%, respectively (P = .006). Patient survival was also significantly lower 94.1% vs. 96.4% and 82.1% vs. 92.2%, respectively, (P = .001). Conclusion: A higher value of the donor''s terminal serum creatinine, CIT, IL2mAb induction, PD prior to KT and donor age increased the risk for DGF after CD-KT. DGF significantly lowered kidney allograft and patient survivals at 1 and 5 years after transplantation among the Thai population. [Copyright &y& Elsevier]

Objectives: To evaluate the prevalence and risk factors of anal squamous intraepithelial lesions (ASIL), the putative anal cancer precursor, in Asian HIV positive and HIV negative men who have sex with men (MSM).Methods: Men who underwent anal Pap smear reported clinical, sociodemographic and behavioural information collected through questionnaire and interview between January 2007 and April 2008. Chi(2) and logistic regression were used to evaluate ASIL prevalence and risk factors among HIV positive and HIV negative MSM.Results: Of the 174 MSM (mean age 32.1 years), 118 (67.8%) were HIV positive. Overall, 27% had abnormal anal cytology: 13.2% had atypical squamous cells of undetermined significance (ASC-US), 11.5% had low-grade squamous intraepithelial lesion (LSIL) and 2.3% had high-grade squamous intraepithelial lesion (HSIL). Prevalence of ASIL was higher among HIV positive than HIV negative MSM (33.9% vs 12.5%; p = 0.003). Among HIV positive MSM, 16.1% had ASC-US, 14.4% had LSIL and 3.4% had HSIL and 7.1%, 5.4% and 0% in HIV negative MSM, respectively. Anal condyloma was detected in 22% of HIV positive and 16.1% (9/56) of HIV negative MSM (p = 0.5). In HIV positive MSM, anal condyloma (OR 3.42, 95% CI 1.29 to 9.04; p = 0.01) was a significant risk factor for ASIL. Highly active antiretroviral therapy use and CD4+ T cell count were not associated with ASIL.Conclusions: One-third of HIV positive and 12.5% of HIV negative MSM had ASIL. Thus, as greater numbers of HIV positive MSM live longer due to increasing access to HAART worldwide, effective strategies to screen and manage anal precancerous lesions are needed. [ABSTRACT FROM AUTHOR]

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

We analyzed the association between single nucleotide polymorphisms in IL-12 and IL-18 genes in disease susceptibility and severity of SLE in Thais. A weak association was observed between A allele of the IL-12 gene at the 3′ untranslated region in SLE patients with proteinuria (OR = 1.89, 95% CI = 1.05–3.40, P = 0.02, Pc = 0.06). In addition, we found a significant association between C allele of IL-18 (−137) with arthritis (OR = 6.88, 95% CI = 1.54–42.93, P = 0.003, Pc = 0.009). The presence of one C allele (C/C+C/G) was associated with significant OR of 8.72 (95% CI = 1.83–56.71, P = 0.001, Pc = 0.003). Interestingly, we found the combined effect between the G/C genotype of IL-18 (−137) and the A/A genotype of IFNG (+874) gene causing susceptibility of arthritis in SLE patients (OR = 13.22, 95% CI = 1.56–291.66, P = 0.004). [ABSTRACT FROM AUTHOR]

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

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

Background: Currently, there is a lack of evidence to guide optimal care for 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 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 involved an MDCT (nephrologists, nurses, nutritionists, and pharmacists). The primary outcome was the feasibility outcomes; comprising of the rates of loss to follow up, 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 the 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 feasibility outcomes; 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 were no differences in the other renal outcomes between the two groups.Conclusions: Comprehensive care by an MDCT is feasible and could be implemented for severe AKI survivors. MDCT involvement also yields better reduction of the UACR and better blood pressure control. Trial registration Clinicaltrial.gov: NCT04012008 (First registered July 9, 2019). [ABSTRACT FROM AUTHOR]

Abstract: Background: Kidney transplantation is the most performed solid organ transplantation in Thailand. Over 4000 patients have received kidney transplantation from 23 centers within the kingdom. This study sought to demonstrate the causes of graft loss and death in Thai patients receiving kidney transplant during the past decade. Patients and Methods: The Thai Transplant Registry database was used to evaluate the causes of graft loss and death. This database was established since 1997, a total of 2298 kidney transplants were available for analysis. Graft loss was defined as return to dialysis, graft removal, retransplantation, or death of the recipients. Patient survival was analyzed by all deaths. Results: Among 2298 recipients, 59% received organs from deceased donors. The mean age at transplantation was 42 years (SD 12) and 61% were male. The most common identified causes of the end-stage renal disease were chronic glomerulonephritis (25.3%) and hypertensive nephropathy (11.3%); half of those were unknown. Actuarial graft survival rates at 1 and 5 years were 89% and 73%, respectively. The common causes of graft loss were chronic allograft nephropathy (53%), acute rejection (15%), death with a functioning graft (15%), and transplant renal artery diseases (7%). The greatest proportion (64%) of deaths was infection owing to septicemia and/or pulmonary infection. The others were from cardiovascular deaths (12%), liver disease (6%), and malignancy (4%). Conclusion: Graft survival rates were comparable with previous reports. However, the proportion of death with functioning graft and cardiovascular death as a cause of graft and patient loss is lower than that of Caucasian populations. [Copyright &y& Elsevier]

Abstract: Background: Calcineurin inhibitor (CNI) toxicity is a common cause of chronic allograft nephropathy. Although de novo sirolimus (SRL) with CNI minimization may provide better graft function, studies in Asian recipients are lacking. Aim: We sought to determine the 1-year outcomes of renal transplant patients who received a de novo SRL-based regimen with CNI minimization. Patients and methods: A single-center, prospective study of de novo SRL-based, reduced-dose cyclosporine regimen was performed from 2004 to 2007. The control group was a historical cohort of a cyclosporine-based regimen (cyclosporine, prednisolone, and mycophenolate mofetil). The 1-year outcome parameters included renal function, rate of acute rejection, biopsy-proven CNI toxicity, graft and patient survivals. Results: The SRL-based regimen achieved 100% 1-year graft and patient survivals. The renal function was comparable between the SRL-based and CNI-based regimens (serum creatinine 1.32 ± 0.45 and 1.45 ± 0.43 mg/dL; P = .27). The rate of biopsy-proven acute rejection was comparable (9.5% and 13%; P = .68). The SRL-based regimen had a higher rate of biopsy-proven CNI toxicity (28.5% and 9.7%; P = .03). Conclusions: De novo SRL-based regimen with CNI minimization provides excellent transplant outcomes. The strategy to minimize or withdraw CNIs may achieve excellent graft function. A prospective study targeting lower CNI trough levels in Asian transplant recipients is required. [Copyright &y& Elsevier]

Background: Immune 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). Methods: We 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. Results: A total of 800 ART-naïve patients with baseline CD4/CD8 ratio of < 0.8 who started combination ART, and had sustained virological suppression were enrolled. Participants were on ART for a median of 8.9 years and virologically suppressed for 6.1 years. The probabilities of CD4/CD8 normalization at 2, 5 and 10 years after virological suppression were 5.1%, 18.6% and 39.1%, respectively. Factors associated with normalization in multivariate analysis were female sex (hazard ratio [HR]: 2.47, 95% CI 1.71–3.56, p < 0.001) and baseline CD4 counts ≥ 350 cells/mm3 (HR: 3.62, 95% CI 2.36–5.55), p < 0.001) vs. < 200 cells/mm3 as 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 < 0.01) and current CD4/CD8 ratio < 0.3 (HR: 3.02, 95% CI 1.27–7.21, p = 0.01) or between 0.3 and 0.45 (HR: 2.03, 95% CI 1.03–3.98, p = 0.04) vs. > 0.45 were independently associated with higher risk of progression to NAEs in the multivariate analysis. Conclusions: Our 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 registration HIV-NAT 006 cohort, clinical trial number: NCT00411983 [ABSTRACT FROM AUTHOR]

Abstract: Background: The Thai Kidney Transplant (TKT) program was launched in October 2008 to promote transplantation among previously disadvantaged populations, using fixed-rate provider payment. This study investigated if the introduction of this program could alter the natural practice trends of immunosuppressive drug use. Methods: Data from the Thai Transplantation Registry were analyzed. The change in trend of immunosuppressive use was assessed using the multivariate adaptive regression splines (MARS) technique. Results: During 1987–2012, 3975 kidney transplantations were done. The average age of patients was 42 years and 62% were male. Chronic glomerulonephritis accounted for one third of those with known causes of end-stage renal disease (ESRD). Eighty-six percent were on hemodialysis before transplantation. Prednisolone was used in 95.87% of all transplant recipients, whereas calcineurin inhibitors (CNIs), mycophenolates (MPAs), azathioprine (AZA), and mammalian target of rapamycin inhibitors (mTORis) were used in 95.67%, 64.22%, 12.25%, and 2.31%, respectively. Overall use after 2008 was decreased for AZA (18.16% to 3.40%) and mTORis (2.86% to 1.5%) but increased for MPAs (50.80% to 84.34%), CNIs (95.43% to 96.04%), and prednisolone (95.60% to 96.29%), as compared with before the program inception. The slopes of use trends of AZA, MPAs, and CNIs did not significantly marginally differ from their natural trends before the program inception (P = .496, .108, and .741, respectively). However, the natural increasing use trend of mTORis significantly changed to a decreasing pattern after the introduction of the TKT program (P = .018). Conclusion: Fixed-rate provider payment might interfere with the natural practice trends of immunosuppressive drug use. [Copyright &y& Elsevier]

Background: Drug resistance is a challenge for the global control of tuberculosis. We examined mortality in patients with tuberculosis from high-burden countries, according to concordance or discordance of results from drug susceptibility testing done locally and in a reference laboratory.Methods: This multicentre cohort study was done in Côte d'Ivoire, Democratic Republic of the Congo, Kenya, Nigeria, South Africa, Peru, and Thailand. We collected Mycobacterium tuberculosis isolates and clinical data from adult patients aged 16 years or older. Patients were stratified by HIV status and tuberculosis drug resistance. Molecular or phenotypic drug susceptibility testing was done locally and at the Swiss National Center for Mycobacteria, Zurich, Switzerland. We examined mortality during treatment according to drug susceptibility test results and treatment adequacy in multivariable logistic regression models adjusting for sex, age, sputum microscopy, and HIV status.Findings: We obtained M tuberculosis isolates from 871 patients diagnosed between 2013 and 2016. After exclusion of 237 patients, 634 patients with tuberculosis were included in this analysis; the median age was 33·2 years (IQR 26·9-42·5), 239 (38%) were women, 272 (43%) were HIV-positive, and 69 (11%) patients died. Based on the reference laboratory drug susceptibility test, 394 (62%) strains were pan-susceptible, 45 (7%) monoresistant, 163 (26%) multidrug-resistant (MDR), and 30 (5%) had pre-extensively or extensively drug resistant (pre-XDR or XDR) tuberculosis. Results of reference and local laboratories were concordant for 513 (81%) of 634 patients and discordant for 121 (19%) of 634. Overall, sensitivity to detect any resistance was 90·8% (95% CI 86·5-94·2) and specificity 84·3% (80·3-87·7). Mortality ranged from 6% (20 of 336) in patients with pan-susceptible tuberculosis treated according to WHO guidelines to 57% (eight of 14) in patients with resistant strains who were under-treated. In logistic regression models, compared with concordant drug susceptibility test results, the adjusted odds ratio of death was 7·33 (95% CI 2·70-19·95) for patients with discordant results potentially leading to under-treatment.Interpretation: Inaccurate drug susceptibility testing by comparison with a reference standard leads to under-treatment of drug-resistant tuberculosis and increased mortality. Rapid molecular drug susceptibility test of first-line and second-line drugs at diagnosis is required to improve outcomes in patients with MDR tuberculosis and pre-XDR or XDR tuberculosis.Funding: National Institutes of Allergy and Infectious Diseases, Swiss National Science Foundation, Swiss National Center for Mycobacteria. [ABSTRACT FROM AUTHOR]

Summary Objectives To evaluate the applicability and accuracy of the urine lipoarabinomannan (LAM) test in tuberculosis (TB)/HIV co-infected patients and HIV-negative patients with disseminated TB. Methods Frozen urine samples obtained at baseline from patients in the TB research cohort with proven culture-positive TB were selected for blinded urine LAM testing. One hundred and nine patients were categorized into four groups: (1) HIV-positive patients with TB; (2) HIV-negative patients with disseminated TB; (3) HIV-negative immunocompromised patients with TB; and (4) patients with diseases other than TB. The sensitivity of urine LAM testing for culture-positive TB, specificity of urine LAM testing for patients without TB, positive predictive value (PPV), and negative predictive value (NPV) were assessed. Results The sensitivity of the urine LAM test in group 1 patients with a CD4 T-cell count of >100, ≤100, and ≤50 cells/mm 3 was 38.5%, 40.6%, and 45%, respectively. The specificity and PPV of the urine LAM test were >80%. The sensitivity of the test was 20% in group 2 and 12.5% in group 3, and the specificity and PPV were 100% for both groups. A positive urine LAM test result was significantly associated with death. Conclusions This promising diagnostic tool could increase the yield of TB diagnosis and may predict the mortality rate of TB infection, particularly in TB/HIV co-infected patients. [ABSTRACT FROM AUTHOR]

Background Cytomegalovirus (CMV) infection significantly causes morbidity in kidney transplant (KT) recipients. This study aims to investigate the incidence, timing, and risk factors of CMV infection in KT recipients. Methods This is a single-center retrospective study at a tertiary referral hospital. Patients who underwent KT from January 2012 to September 2014 were included. CMV infection was defined as the presence of CMV measured by polymerase chain reaction. Logistic regression analysis was performed to assess independent risk factors of CMV infection after KT. Results Of 121 KT patients enrolled, 120 patients had CMV D + /R + serostatus, and 1 had D-/R + . CMV infection occurred in 33 (27.2%) of patients with a median follow-up time of 16 (IQR 4–25) months. Of those, 25 had CMV viremia and 8 had CMV disease mainly involving the gastrointestinal system. In total, 86% of CMV cases occurred within 3 months. All recipients received anti–IL-2 receptor antibody (IL-2 RA), low-dose rabbit antithymocyte globulin (rATG; total of 1.5 mg/kg), or standard-dose rATG (1.5 mg/kg/day for 3–5 days) for induction. Of those, the incidences of CMV infection were 19.6%, 50%, and 67%, respectively. Preemptive strategy was used in all but 1 patient in the IL-2 RA and low-dose rATG group, whereas universal prophylaxis was given in 67% of patients in the standard-dose rATG group. Independent risk factors of CMV infection were older recipient age (per 10-year increase, OR 1.5; 95% CI 1.04–2.23), and induction with standard (OR 8.19; 95% CI 2.29–34) and low-dose rATG (OR 3.87; 95% CI 1.06–12.23). Conclusions More than 25% of KT recipients developed CMV infection within 6 months after KT. The risk is increased in older recipients and induction with rATG. The level of CMV risk in low-dose rATG is 52% lower than in standard-dose rATG. In a limited-resource setting such as Thailand, deferred or preemptive strategy may be acceptable in patients who received IL-2 RA and low-dose rATG, while prophylactic therapy should be given to patients who received standard-dose rATG. [ABSTRACT FROM AUTHOR]

Background: Cytochrome P450 (CYP) 3A4 and 3A5 are major isoforms involved in the metabolism of tacrolimus, with the CYP3A5 gene being more poly-morphic. It is hypothesized that individual variation in the metabolism of tacrolimus drug may result from genetic polymorphism of CYP3A5. It has been re-ported that the clearance of tacrolimus in patients with the CYP3A5*1 allele was ~2.5-fold greater than that in those with the CYP3A5*3/*3 genotype. Recent data have also shown that polymorphism in exon 26 (C3435T) of the multidrug resistance gene (MDR1) was correlated with the expression level and function of P-glycoprotein in the lower duodenum, making the relationship between polymorphism of MDR1 and the effective dose of tacrolimus a source of controversy. Objectives: This study investigated the influence of genetic polymorphisms of CYP3A5 and MDR1 on the dose requirements for the induction and maintenance phases of tacrolimus therapy in kidney transplant recipients. Methods: Sixty-eight kidney transplant recipients were enrolled, and their clinical and laboratory data were retrospectively reviewed after 6 months of tacrolimus administration. Genotypes of CYP3A5*1 and CYP3A5*3 and exon 26 of MDR1 (C3435T) were determined by the single-nucleotide polymor-phism genotyping method. Results: The frequencies of CYP3A5*3/*3, CYP3A5*1/*3, and CYP3A5*1/*1 were 44.1%, 35.3%, and 20.6%, respectively. The mean dose of tacrolimus required for the induction phase was significantly greater in the CYP3A5*1/*1 group (0.142 [0.050] mg/kg/d) than that required in the CYP3A5*1/*3 group (0.097 [0.040] mg/kg/d; P -- 0.072) and in the CYP3A5*3/*3 group (0.077 [0.020] mg/kg/d; P -- 0.005). The maintenance dose of tacrolimus required in the CYP3A5*1/*1 group (0.12 [0.03] mg/kg/d) was 1.3-fold higher than that in the CYP3A5*1/*3 group (0.09 [0.03] mg/kg/d; P = 0.018) and 2.4-fold higher than in the CYP3A5*3/*3 group (0.05 [0.02] mg/kg/d; P < 0.0001). No statisti-cally significant relationship was observed between the doses of tacrolimus required for the induction and maintenance phases and MDR1 polymorphism. Conclusion: Determination of the CYP3A5 geno-type would be helpful in the design of adequate immunosuppressive treatment and in lowering tox-icity by predicting the doses of tacrolimus required for the induction and maintenance phases in ind-ividual kidney transplant recipients. [ABSTRACT FROM AUTHOR]

Abstract: Introduction: Kidney retransplantation is a high-risk procedure that is increasingly performed because of previous graft failure. The aim of this study was to determine the long-term outcomes of kidney retransplantations compared with first kidney transplantations under the current era of immunosuppression. Methods: Since the first retransplantation in Thailand was performed in 1993, this study included all consecutive cases registered in the Thai Transplantation Registry database from January 1993 to December 2011. A total of 3337 kidney transplantations were available for the analysis. Graft loss was defined as a return to dialysis or graft removal. Death with a functioning graft was censored. Results: Of 3337 kidney transplantations during the study period, 113 were second and 3 were third transplantations. Among these 116 retransplantations, the most common identified causes of end-stage renal disease were chronic glomerulonephritis (38.8%), followed by hypertensive nephropathy (13.0%), diabetic nephropathy (6.0%), and lupus nephritis (1.7%). The retransplantation recipients were older (mean age, 46.2 ± 12.8 years) than the first transplantation group (mean age, 42.2 ± 12.8 years). The proportion of living-related kidney transplantations and male sex were similar between first and retransplantation recipients. Fourteen percent of retransplantation recipients showed high immunologic risk as defined by current panel reactive antibodies ≥30% compared with 3% of those in the first transplantation group (P < .001). The percentages of induction therapy with antithymocyte globulin and anti–interleukin-2 antibody in the retransplantation and first transplantation groups were 18.3% versus 4.3% and 60.0% versus 32.6%, respectively. The graft survival rates (95% confidence interval [CI]) at 1, 5, and 10 years were 88.6% (80.7–93.3), 87.3% (79.1–92.5), and 74.4% (53.7–86.9) among retransplantation, versus 95.0% (94.1–95.7), 87.0% (85.5–88.5), and 70.7% (67.4–73.8) among first transplantation groups, respectively (P = .63). Patient survival rates were not different between first and retransplantation groups (P = .42). The leading cause of graft loss in the retransplantation group was chronic allograft nephropathy (22%), whereas infection (57%) was the major cause of death in this group. Conclusion: The 10-year patient and graft survival rates of kidney retransplantation were acceptable. The combination of induction therapy with a calcineurin inhibitor and a mycophenolate mofetil/mychophenolic acid–based regimen lead to outcomes comparable to first kidney transplantations among our cohort of 3337 patients. [Copyright &y& Elsevier]

Malnutrition is a risk factor of sarcopenia in the elderly. During the COVID-19 pandemic, limited transportation and supply chain disruptions restricted access to nutritious foods. We assessed the nutritional status and sarcopenia risk in older people living with HIV (PLWH) on combination antiretroviral therapy in Thailand. This study was a hospital-based cohort among virally suppressed older PLWH who came for routine HIV clinic visits. The mini nutritional assessment (MNA), body composition analysis and 5-time chair stand test (CST) were performed to assess the nutritional status, muscle mass and physical performance, respectively. A total of 177 PLWH were enrolled (57.60% male). The median age was 58 years (IQR 55-62 years). Thirty-five participants (19.8%) were at risk of developing sarcopenia, and 28.2% had abnormal nutritional status. Muscle mass correlated positively with nutritional scores (r = 0.355, p < 0.001) but negatively with 5-time CST duration (r = -0.173, p = 0.021). In the multivariate model, muscle mass was associated with age, sex, mid-arm circumference, calf circumference and 5-time CST duration. In a well-viral-suppressed older Asian PLWH cohort, given the positive correlation between nutritional status and muscle mass, the nutritional status of older PLWH should be routinely evaluated and monitored.

Ravidasvir (RDV) is a novel NS5A inhibitor that exhibits potent pan-genotypic inhibition of hepatitis C virus (HCV) replication. Sofosbuvir (SOF) plus RDV was demonstrated to be efficacious and safe in adults with active HCV infection, including those living with HIV (LWHIV), in the STORM-C-1 trial. We assessed the population pharmacokinetics (PK) of RDV in a sub-study nested within STORM-C-1 conducted in Thailand and Malaysia. SOF (400 mg) plus RDV (200 mg) was administered orally once daily for 12 weeks to adults with chronic HCV infection, but without cirrhosis and for 24 weeks to those with compensated cirrhosis. Intensive and sparse PK samples were collected at 4, 8, and 12 weeks after treatment initiation. Population PK parameters of RDV and the impact of covariates were evaluated using nonlinear mixed-effects modeling. Five hundred ninety-four participants were included, 235 (40%) had compensated cirrhosis, and 189 (32%) were LWHIV. RDV plasma concentrations were best described by a two-compartment model with first-order elimination. Oral clearance (CL/F) and volume of distribution (Vd/F) parameters were allometrically scaled on fat-free mass. Concomitant antiretroviral treatment (ART) increased RDV CL/F by 30%-60%, with efavirenz-based ART having the largest impact. Females had 16% lower RDV CL/F than males, and higher albumin levels reduced RDV central volume of distribution. While several covariates impact RDV CL/F and Vd/F, the effect on RDV exposures was not clinically relevant based on the efficacy data reported in this diverse Asian adult population. There were no meaningful drug-drug interactions in adults LWHIV on ART., Competing Interests: C.M., I.R., A.S., and J.-Y.G. are employed by the DNDi. All other authors declare no competing interests.

Background: Chronic hepatitis C virus (HCV) infection contributes to substantial morbidity and mortality among adults living with HIV. Cascades of HCV care support monitoring of program performance, but data from Asia are limited. We assessed regional HCV coinfection and cascade outcomes among adults living with HIV in care from 2010-2020., Methods: Patients ≥18 years old with confirmed HIV infection on antiretroviral therapy (ART) at 11 clinical sites in Cambodia, China, India, Indonesia, South Korea, Thailand and Vietnam were included. HCV- and HIV-related treatment and laboratory data were collected from those with a positive HCV antibody (anti-HCV) test after January 2010. An HCV cascade was evaluated, including proportions positive for anti-HCV, tested for HCV RNA or HCV core antigen (HCVcAg), initiated on HCV treatment, and achieved sustained virologic response (SVR). Factors associated with screening uptake, treatment initiation, and treatment response were analyzed using Fine and Gray's competing risk regression model., Results: Of 24,421 patients, 9169 (38%) had an anti-HCV test, and 971 (11%) had a positive result. The proportion with positive anti-HCV was 12.1% in 2010-2014, 3.9% in 2015-2017, and 3.8% in 2018-2020. From 2010 to 2014, 34% with positive anti-HCV had subsequent HCV RNA or HCVcAg testing, 66% initiated HCV treatment, and 83% achieved SVR. From 2015 to 2017, 69% with positive anti-HCV had subsequent HCV RNA or HCVcAg testing, 59% initiated HCV treatment, and 88% achieved SVR. From 2018 to 2020, 80% had subsequent HCV RNA or HCVcAg testing, 61% initiated HCV treatment, and 96% achieved SVR. Having chronic HCV in later calendar years and in high-income countries were associated with increased screening, treatment initiation or achieving SVR. Older age, injecting drug use HIV exposure, lower CD4 and higher HIV RNA were associated with reduced HCV screening or treatment initiation., Conclusions: Our analysis identified persistent gaps in the HCV cascade of care, highlighting the need for focused efforts to strengthen chronic HCV screening, treatment initiation, and monitoring among adult PLHIV in the Asia region., Competing Interests: AHS has received grants to her institution from ViiV Healthcare and Gilead Sciences. Other authors have declared that no competing interests exist. This does not alter our adherence to PLOS ONE policies on sharing data and materials., (Copyright: This is an open access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication.)