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Objectives: The aim of this study was to investigate the association between taste and smell losses and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, and to elucidate whether taste preference influences such taste loss. Methods: A matched case–control study was conducted in 366 Thai participants, including 122 who were confirmed SARS-CoV-2-positive by RT-PCR (case group) and 244 who were SARS-CoV-2-negative (control group). Taste, smell, and appetite changes were assessed by self-reported visual analog scale. Preference for sweet, salty, umami, sour, bitter, and spicy were judged using the validated TASTE-26 questionnaire. Results: Partial taste and smell losses were observed in both groups, while complete losses (ageusia and anosmia) were detected only in the case group. Moreover, only ageusia and anosmia were associated with SARS-CoV-2 positivity (P < 0.001, odds ratio of 14.5 and 27.5, respectively). Taste, smell, and appetite scores were more severely reduced in the case group (P < 0.0001). Multivariate analysis showed that anosmia and ageusia were the best predictors of SARS-CoV-2 positivity, followed by appetite loss and fever. Simultaneous losses of taste and smell but not taste preferences were associated with SARS-CoV-2 positivity (P < 0.01, odds ratio 2.28). Conclusions: Complete, but not partial, losses of taste and smell were the best predictors of SARS-CoV-2 infection. During the current COVID-19 pandemic, healthy persons with sudden simultaneous complete loss of taste and smell should be screened for COVID-19.

Among 11 patients in Thailand infected with severe acute respiratory syndrome coronavirus 2, we detected viral RNA in upper respiratory specimens a median of 14 days after illness onset and 9 days after fever resolution. We identified viral co-infections and an asymptomatic person with detectable virus RNA in serial tests. We describe implications for surveillance.

Background Favipiravir is a promising drug for COVID-19, but evidence from a robust clinical trial is limited. Objective To describe the demographics, clinical characteristics, and various antiviral treatment regimens (with and without favipiravir) of patients with severe and nonsevere COVID-19. Method We conducted a retrospective observational study in all COVID-19 patients admitted at Bamrasnaradura Infectious Diseases Institute (BIDI) from January 8 to March 30, 2020. We compared the demographics, clinical characteristics, and various antiviral treatment regimens of 12 severe and 29 nonsevere COVID-19 patients in Thailand. Results Adjunctive favipiravir was given to only severe cases. The median length of hospitalization of patients either receiving favipiravir or not receiving favipiravir was not significantly different (P = 0.8549), but those who received adjunctive favipiravir became reverse transcriptase–polymerase chain reaction negative 2 days sooner than the other group (median: 6 days vs. 8 days; P = 0.1125). Conclusion The findings suggested that adjunctive favipiravir might not be effective for patients with severe COVID-19, but further studies with larger sample sizes are needed.

Background Individuals with end-stage renal disease have a higher risk of hepatitis C virus (HCV) acquisition during long-term hemodialysis (HD). Our report was designed to investigate HCV prevalence and genotype, in addition to the clinical use of HCV core antigen (HCVcAg), within multiple HD facilities in Thailand. Methods This cross‐sectional report was investigated between January and June 2019. HCV infection was assessed by anti-HCV and confirmed active infection by measuring HCV RNA and HCVcAg. HCV genotype was determined by phylogenetic analysis using nucleotide sequences of NS5B region. Results Overall, 140 of 3,305 (4.2%) patients in 15 dialysis centers had anti-HCV positive. Among them, HCV RNA was further assessed in 93 patients and was detectable in 59 (63.4%) persons. Considering HCV viremia, HCVcAg measurement exhibited high accuracy (96.8%), sensitivity (94.9%) and specificity (100%) in comparison with HCV RNA testing. Moreover, individuals infected with HCV received a longer duration of dialysis vintage when compared to anti-HCV negative controls. The major sub-genotypes were 1a, 1b, 3a, 3b, 6f and 6n. Regarding phylogenetic analysis, there were 7 clusters of isolates with high sequence homology affecting 17 individuals, indicating possible HCV transmission within the same HD centers. Conclusions HCV frequency and common sub-genotypes in HD centers were different from those found in the Thai general population. HCVcAg might be an alternate testing for viremia within resource-limited countries. Enhanced preventive practices, dialyzer reuse policy and better access to antiviral therapy are crucial for HCV micro-elimination within HD facilities.

Anxiety and depression in hospitalized COVID-19 patients in Thailand during the first wave of the pandemic were investigated. Thai version of Hospital Anxiety and Depression Scale (HADS) was chosen as an instrument for evaluation. Thirty-two voluntary participants completed the questionnaire. Three (9.4%) respondents had abnormal anxiety sub-scale scores while no respondents had abnormal depression sub-scale scores. There was no statistical demographic difference between the anxiety and non-anxiety groups.

Early in January 2020, Thailand became the first country where a Coronavirus disease 19 (COVID‐19) patient was identified outside China. In this study, 23 whole genomes of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS‐CoV‐2) from patients who were hospitalized during January to March 2020 were analyzed, along with their travel histories. Six lineages were identified including A, A6, B, B.1, B.1.8 and B.58; lineage A.6 was dominant. Seven patients were from China who travelled to Thailand in January and early of February, five of them were infected with B lineage virus, the other two cases were infected with different lineages including A and A.6. These findings represent clear evidence of the early introduction of diverse SARS‐CoV‐2 clades in Thailand. This article is protected by copyright. All rights reserved.

A Thai Taxi Driver with Covid-19 The authors describe a taxi driver in Thailand who was infected with the novel coronavirus, potentially from passengers who were tourists from China, in January 202...

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

Clinical spectrum of Coronavirus Disease 2019 (COVID-19) remains unclear, especially with regard to the presence of pneumonia. We aimed to describe the clinical course and final outcomes of adult patients with laboratory-confirmed COVID-19 in the full spectrum of disease severity. We also aimed to identify potential predictive factors for COVID-19 pneumonia. We conducted a retrospective study among adult patients with laboratory-confirmed COVID-19 who were hospitalized at Bamrasnaradura Infectious Diseases Institute, Thailand, between January 8 and April 16, 2020. One-hundred-and-ninety-three patients were included. The median (IQR) age was 37.0 (29.0–53.0) years, and 58.5% were male. The median (IQR) incubation period was 5.5 (3.0–8.0) days. More than half (56%) of the patients were mild disease severity, 22% were moderate, 14% were severe, and 3% were critical. Asymptomatic infection was found in 5%. The final clinical outcomes in 189 (97.9%) were recovered and 4 (2.1%) were deceased. The incidence of pneumonia was 39%. The median (IQR) time from onset of illness to pneumonia detection was 7.0 (5.0–9.0) days. Bilateral pneumonia was more prevalent than unilateral pneumonia. In multivariable logistic regression, increasing age (OR 2.55 per 10-year increase from 30 years old; 95% CI, 1.67–3.90; p, Author summary This report describes the clinical course and final clinical outcomes of the full spectrum of disease severity of Coronavirus Disease 2019 (COVID-19) and evaluates risk factors of pneumonia in 193 laboratory-confirmed cases of COVID-19 in the Bamrasnaradura Infectious Diseases Institute, Thailand. The majority of patients with COVID-19 had mild disease. COVID-19 pneumonia was found in approximately 40% of patients. Older age, obesity, and higher grade of fever at presentation were independent risk factors of pneumonia in adult patients with COVID-19. Most patients in our cohort recovered and were discharged from hospital (recovery rate, 98%). Our findings can help the public health systems to estimate the burden of the disease and identify vulnerable patients in a timely manner.

HIV-infected patients receiving antiretroviral therapy have increased risk of metabolic syndrome, including dyslipidemia. In this study, we determined whether individual nutritional counseling reduced dyslipidemia, particularly low-density lipoprotein (LDL) cholesterol, among HIV-infected patients with dyslipidemia not currently taking lipid-lowering medication. We conducted a randomized 24-week trial among HIV-infected patients with dyslipidemia who were on antiretroviral therapy and were eligible to initiate therapeutic lifestyle changes according to the Thai National Cholesterol Education Program. Participants were randomly assigned to an intervention group that received individual counseling with a nutritionist for seven sessions (baseline, weeks 2, 4, 8, 12, 18, and 24) and a control group that received standard verbal diet information at baseline and nutritional counseling only at week 24. A 24-h recall technique was used to assess dietary intake for both groups at baseline and week 24. Lipid profile (total cholesterol, LDL, high-density lipoprotein (HDL), and triglyceride) was measured at baseline and after 12 and 24 weeks of therapy. An intention-to-treat and linear mixed model were used. Seventy-two patients were randomly assigned, and 62 (86%) participants completed their lipid profile test. After 12 weeks of follow-up, there were significant reductions in the intervention group for total cholesterol (-14.4 ± 4.6 mg/dL, P = .002), LDL cholesterol (-13.7 ± 4.1 mg/dL, P = .001), and triglyceride (-30.4 ± 13.8 mg/dL, P = .03). A significant reduction in LDL cholesterol was also observed in the control group (-7.7 ± 3.8 mg/dL, P = .04), but there were no significant differences in change of mean lipid levels between the groups at 12 weeks of follow-up. After 24 weeks, participants assigned to the intervention group demonstrated significantly greater decreases in serum total cholesterol (-19.0 ± 4.6 vs. 0.2 ± 4.3 mg/dL, P = .003) and LDL cholesterol (-21.5 ± 4.1 vs. -6.8 ± 3.8 mg/dL, P = .009). There were no significant changes in HDL cholesterol or triglyceride levels in either group.

Adolescence may affect adherence and response to highly active antiretroviral therapy (HAART). Limited data are available regarding the long-term treatment outcomes of perinatal HIV-infected adolescents.Data from perinatally acquired HIV-infected Thai children who started first-line nonnucleoside analog-based HAART before 18 years of age and treated for ≥24 weeks were analyzed. Children were categorized by age at HAART initiation; age3 years, 3-9 years, early adolescence (10-13 years) and middle adolescence (14-16 years). CD4 and HIV-RNA were monitored every 6-12 months. Virologic failure (VF) was defined as HIV-RNA≥1000 copies/mL after ≥24 weeks of HAART.Of 840 children, 68% were in pre-adolescence. Median baseline CD4% was 7.9%. Use of nevirapine versus efavirenz was 77:23%. Median duration of nonnucleoside reverse transcriptase inhibitor-based HAART was 5.6 years. No differences between groups were observed for rate of HIV-RNA50 copies/mL (68%, P=0.18) and rate of VF (28%, P=0.82), median time to VF (22 months, P=0.13). Incidence of VF per 100 child-year in children age3 years, 3-9 years, early adolescence and middle adolescence were 7.9, 4.7, 7.4 and 10.8, respectively (P=0.012). Median adherence by pill count was 97.3% (P=0.23). By multivariate analysis, predictors for VF were age at HAART initiation of3 years (HR: 1.73, 95% CI: 1.18-2.55), age 10-16 years (HR: 1.47, 95% CI: 1.09-1.97), and nevirapine use (HR: 1.63, 95% CI: 1.14-2.32).VF rates were observed in one-third of long-term treated Thai children on first-line HAART. Age 3-9 years at HAART initiation was associated with less VF compared with those younger or older, whereas children who used nevirapine had higher VF.

Metabolic syndrome (MS), a group of interrelated risk factors for cardiovascular diseases (CVD) and type 2 diabetes, has been increasingly reported among HIV-infected patients. Data on the prevalence and risk factors for MS among HIV-1 infected Thai adults are limited. The study collected cross-sectional data from 580 HIV-1 infected adults-46.2% were men and 71% were antiretroviral therapy (ART)-experienced. The majority (78.8%) of them used non-nucleoside reverse transcriptase inhibitor-based regimens. Data on lipid profiles, fasting blood glucose, CD4 count, HIV RNA, antiretroviral therapy (ART), anthropometry, food intake, and exercise were recorded. MS was defined using American Heart Association/National Heart Lung and Blood Institute criteria. Overall prevalence of MS was 22.2%; 15.9% in ART-naïve group vs. 24.9% in ART-experienced group, p = 0.018. Significant risk factors for MS in multivariate analyses included age ≥35 years (odds ratio, OR, 4.2, 95%CI 1.6-11.0, p = 0.004), high cholesterol (OR 4.7, 95%CI 1.7-12.9, p = 0.002), and living outside Bangkok (OR 4.2, 95%CI 1.6-10.8, p = 0.003) in the ART-naïve group, and female gender (OR 1.7, 95%CI 1.0-2.8, p = 0.05), lipodystrophy (OR 1.8, 95%CI 1.0-3.0, p = 0.032), high cholesterol (OR 1.9, 95%CI 1.1-3.1, p = 0.015), and food insecurity (OR 1.8, 95%CI 1.0-3.3, p = 0.05) in the ART-experienced group. All variables, except for female gender in the ART-experienced group, remained significantly associated with MS in a model where lipodystrophy was excluded. We concluded that MS was common among HIV-1-infected Thai adults. As HIV-infected patients get older, early screening and intervention, such as ART modification to avoid lipodystrophy, may reduce MS and CVD-related morbidities and mortalities in long-term care.

SummaryObjectiveTo describe the outcomes of antiretroviral therapy (ART) in a large cohort of HIV-infected children in Thailand.MethodsThe data were obtained from four collaborative referral sites around the country. Data from 2008 to March 2011 were collected prospectively, and data before 2008 were collected retrospectively.ResultsOf the 1139 children, 599 (52.6%) were female, and the duration of ART was a median 2.9 years (interquartile range (IQR) 3.3–5.5 years). At ART initiation, the median age was 7.1 years (IQR 3.4–10.0 years), CD4 percentage was 9.0% (IQR 3.0–17.0%), and 61.3% were in World Health Organization (WHO) stage 3 or 4. Seventy-four percent were initiated on an NNRTI-based regimen. The death and lost to follow-up rates were 1.3 (95% confidence interval (CI) 1.1–1.6) and 2.2 (95% CI 1.6–2.6)/100 patient-years of follow-up, respectively. At the last clinic visit of 919 children, the median CD4 percentage was 27.0% (IQR 23.0–32.0%) and 80.2% had HIV-RNA

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/mm

Summary Background Thai patients with HIV have higher exposure to HIV protease inhibitors than do white people and dose reduction might be possible. We compared the efficacy of low-dose with standard-dose ritonavir-boosted atazanavir in virologically suppressed Thai patients with HIV. Methods In this randomised, open-label, non-inferiority trial, we recruited patients aged 18 years or older who were receiving ritonavir-boosted protease-inhibitor-based antiretroviral therapy (ART) with HIV plasma viral loads of less than 50 copies per mL, an alanine aminotransferase concentration of less than 200 IU/L, and a creatinine clearance of at least 60 mL/min from 14 hospitals in Thailand. We excluded patients who had active AIDS-defining disease or opportunistic infections, had a history of an HIV viral load of 1000 copies per mL or more after 24 weeks of any ritonavir-boosted protease-inhibitor-based ART, used concomitant medications that could interact with the study drugs, were pregnant or lactating, had illnesses that might change the effect of the study drugs, or had a history of sensitivity to the study drugs. A biostatistician at the study coordinating centre randomly allocated patients (1:1) to switch the protease inhibitor for oral atazanavir 200 mg and ritonavir 100 mg or for atazanavir 300 mg and ritonavir 100 mg once daily, both with two nucleoside or nucleotide reverse transcriptase inhibitors at recommended doses. Randomisation was done with a minimisation schedule, stratified by recruiting centre, use of tenofovir, and use of indinavir as a component of the preswitch regimen. The primary endpoint was the proportion of patients with viral loads of less than 200 copies per mL at week 48, and we followed up patients every 12 weeks. Treatments were open label, the non-inferiority margin was −10%, and all patients who received at least one dose of study medication were analysed. This trial is registered with ClinicalTrials.gov, number NCT01159223. Findings Between July 6, 2011, and Dec 23, 2013, we randomly assigned 559 patients: 279 to receive atazanavir 200 mg and ritonavir 100 mg (low dose) and 280 to atazanavir 300 mg and ritonavir 100 mg (standard dose). At week 48, 265 (97·1%) of 273 in the low-dose group and 267 (96·4%) of 277 in the standard-dose group had viral loads of less than 200 copies per mL (difference 0·68; 95% CI −2·29 to 3·65). Seven (3%) of 273 in the low-dose group and 21 (8%) of 277 in the standard-dose group discontinued their assigned treatment (p=0·01). 46 (17%) of 273 participants in the low-dose group and 97 (35%) of 277 in the standard-dose group had total bilirubin grade 3 or higher toxicity (≥3·12 mg/dL; p Interpretation A switch to low-dose atazanavir should be recommended for Thai patients with well controlled HIV viraemia while on regimens based on boosted protease inhibitors. Funding The National Health Security Office and Kirby Institute for Infection and Immunity in Society.

A number of patients have experienced treatment failure while receiving non-nucleoside reverse transcriptase inhibitor (NNRTI)-based antiretroviral therapy (ART), particularly in resource-limited countries. The need remains for clinical data on protease inhibitor (PI)-based regimens in these patients. A retrospective cohort study was conducted among HIV-1-infected patients who had failed NNRTI-based regimens, were naive to protease inhibitors (PIs), and subsequently initiated a salvage PI-based regimen between January 2004 and December 2006. The study period ended on 30 December 2007. One hundred and forty patients received a single-boosted PI +/- optimized background regimen (OBR) and 64 received double-boosted PIs. The median (IQR) duration of follow-up was 19 (13-29) months. The overall virological failure rate at 24 months was 15.2%. No statistically significant difference was detected between the two regimen groups (single-boosted PI +/- OBR 16.4% vs. double-boosted PIs 12.5%, log rank p = 0.818). At the end of the study, the median (IQR) change in CD4 cell counts for patients in the double-boosted PI group was higher than for patients in the single-boosted PI +/- OBR group [149 (53-322) vs. 105 (23-199), respectively, p = 0.012]. Patients receiving double-boosted PI regimens displayed a higher frequency of hypertriglyceridemia than those patients who received a single boosted PI +/- OBR (31% vs. 11%, respectively, p = 0.001). Boosted PI-based regimens showed acceptable virological outcomes among patients who had failed NNRTI-based ART. In the subgroup analysis, patients who received double-boosted PIs demonstrated a superior immunological response but not better virological outcomes compared to the single-boosted PI +/- OBR group.

Objective:Investigation on anxiety, stress, depression, and quality of life (QoL) within STACCATO, a randomised trial of two treatment strategies: CD4 guided scheduled treatment interruption (STI) compared to continuous treatment (CT).Participants:Thai patients with HIV-infection enrolled in the STACCATO trial.Methods:Anxiety, depression assessed by the questionnairesHospital Anxiety and Depression Scale(HADS) and DASS, stress assessed by theDepression Anxiety Stress Scale(DASS), and QoL evaluated by theHIV Medical Outcome Study(MOS-HIV) questionnaires. Answers to questionnaires were evaluated at 4 time-points: baseline, 24 weeks, 48 weeks and at the end of STACCATO.Results:A total of 251 patients answered the HADS/DASS and 241 answered the MOS-HIV of the 379 Thai patients enrolled into STACCATO (66.2 and 63.6% respectively). At baseline 16.3% and 7.2% of patients reported anxiety and depression using HADS scale. Using the DASS scale, 35.1% reported mild to moderate and 9.6% reported severe anxiety; 8.8% reported mild to moderate and 2.0% reported severe depression; 42.6% reported mild to moderate and 4.8% reported severe stress. We showed a significant improvement of the MHS across time (p=0.001), but no difference between arms (p=0.17). The summarized physical health status score (PHS) did not change during the trial (p=0.15) nor between arm (p=0.45). There was no change of MHS or PHS in the STI arm, taking into account the number of STI cycle (p=0.30 and 0.57) but MHS significant increased across time-points (p=0.007).Conclusion:Antiretroviral therapy improved mental health and QOL, irrespective of the treatment strategy.

Background: Generic fixed-dose combination (FDC) antiretroviral therapy (ART) has been widely used in resource-limited settings. Treatment based on these combinations provide low pill burden and are less expensive. Objective: The aim of this study was to determine the long-term effectiveness and metabolic complications of a generic FDC of stavudine (d4T)/lamivudine (3TC)/ nevirapine (NVP), among ART-naive HIV-infected patients. Methods: A prospective study was conducted among patients who were initiated on d4T/3TC/NVP between November 2004 and March 2005. Plasma HIV-1 RNA, CD4 and alanine transaminase were assessed every 12 weeks. Fasting plasma glucose (FPG) and lipid profile were determined at 96 weeks. Adverse events and genotypic drug resistance were recorded. The primary outcome of interest was the proportion of patients who achieved plasma HIV-1 RNA 130 mg/dL, 7 (8.0%) had LDL-C >160 mg/dL, 6 (6.9%) had triglycerides >400 mg/dL, and 2 (2.3%) had FPG >126 mg/dL. Eleven patients (12.6%) had a lactic acid level >2.5 mmol/L. Eight patients (9.2%) needed to take antihypertensive agents. Of 13 patients who developed virologic failure, 76.9% and 61.5% had M184V/I and Y181C/I mutations, respectively. Conclusions: Initiation of this FDC ofd4T/3TC/NVP in these ART-naive patients with advanced HIV infection and low baseline CD4 cell count was effective at 96 weeks of follow-up with regard to virologic and immunologic responses. However, long-term metabolic complications, particularly dyslipidemia, were common and should be closely monitored.

Seventy patients with human immunodeficiency virus (HIV) and tuberculosis coinfection who initiated nevirapine-based antiretroviral therapy and had trough nevirapine levels determined while receiving rifampicin were enrolled in a study. After discontinuation of rifampicin therapy, mean nevirapine levels (+/- standard deviation) increased from 5.4+/-3.5 mg/L to 6.4+/-3.4 mg/L (P=.047), but no nevirapine-related adverse events occurred. There was no statistically significant difference in 60-week antiviral efficacy between these patients and patients receiving nevirapine-based antiretroviral therapy alone (P>.05).

Background In Thailand, the combined generic anti-retroviral drug stavudine/lamivudine/nevirapine (d4T/3TC/NVP) has been used to treat human immunodeficiency virus (HIV)-infected individuals since 2001. Due to relatively frequent adverse effects, d4T gradually has been replaced with tenofovir disoproxil fumarate (TDF). Although the frequency of adverse drug effects with TDF is lower than that with d4T, TDF is known to induce kidney dysfunction, especially in the proximal tubules. It has been reported that renal tubular transporters, including members of the multi-drug resistant (MDR) protein family, are implicated in tenofovir extrusion and may, therefore, confer susceptibility to TDF-induced kidney tubular dysfunction (KTD). We have explored the association between KTD and polymorphisms in genes that encode adenosine triphosphate-binding cassette (ABC)-type MDRs. Methods HIV-infected patients receiving TDF-containing antiretroviral regimens for at least one year were enrolled in the study. The levels of beta2-microglobulin in urine and creatinine (Cr) were measured. Three single-nucleotide polymorphisms, ABCC2 C-24T (rs717620), ABCC2 G1429A (rs2273697), and ABCC4 T4976C (rs1059751), were analyzed using TaqMan SNP genotyping assays. Results A total of 273 HIV-infected patients were recruited. The median number of years of TDF treatment was 5.04 with interquartile range (IQR) of 3.9–6.7. Despite the length of treatment with TDF, 98.5% patients maintained an estimated glomerular filtration rate (eGFR) of >60 mL/min as calculated by the CKD-EPI formula. Fifty-four patients (19.8%) showed beta2-microglobulinuria (median 2636 μg/g Cr with IQR of 1519–13197 μg/g Cr). The allele frequency of ABCC4 T4976C among those 54 patients was 0.602, compared to 0.475 among the 219 remaining patients (p = 0.018). Conclusions Approximately 20% of HIV-infected patients receiving TDF showed beta2-microglobulinuria. The C allele at position 4976 of the ABCC4 gene was associated with beta2-microglobulinuria in this population. This polymorphism may help to identify patients at greater risk for developing TDF-associated KTD.

BACKGROUND: Stopping antiretroviral therapy in patients with HIV-1 infection can reduce costs and side-effects, but carries the risk of increased immune suppression and emergence of resistance. METHODS: 430 patients with CD4-positive T-lymphocyte (CD4) counts greater than 350 cells per muL, and viral load less than 50 copies per mL were randomised to continued therapy (n=146) or scheduled treatment interruptions (n=284). Median time on randomised treatment was 21.9 months (range 16.4-25.3). Primary endpoints were proportion of patients with viral load less than 50 copies per mL at the end of the trial, and amount of drugs used. Analysis was intention-to-treat. This study is registered at ClinicalTrials.gov with the identifier NCT00113126. FINDINGS: Drug savings in the scheduled treatment interruption group, compared with continuous treatment, amounted to 61.5%. 257 of 284 (90.5%) patients in the scheduled treatment interruption group reached a viral load less than 50 copies per mL, compared with 134 of 146 (91.8%) in the continued treatment group (difference 1.3%, 95% CI-4.3 to 6.9, p=0.90). No AIDS-defining events occurred. Diarrhoea and neuropathy were more frequent with continuous treatment; candidiasis was more frequent with scheduled treatment interruption. Ten patients (2.3%) had resistance mutations, with no significant differences between groups. INTERPRETATION: Drug savings with scheduled treatment interruption were substantial, and no evidence of increased treatment resistance emerged. Treatment-related adverse events were more frequent with continuous treatment, but low CD4 counts and minor manifestations of HIV infection were more frequent with scheduled treatment interruption.

Eligibility criteria were (1) having previously failed first-line nonnucleoside reverse transcriptase inhibitor–based regimens and (2) having achieved virologic suppression >6 months while receiving a protease inhibitor (PI)-based regimen as second-line treatment. Eligible participants were randomized to receive either (1) ritonavir-boosted lopinavir (LPV/r) monotherapy (n = 29) or (2) LPV/r with optimized background regimens (OBRs; n = 31). Median duration of viral suppression before randomization was 45 months. At week 48, viral suppression during LPV/r monotherapy was 86.2% and did not differ from the suppression achieved with LPV/r with OBRs (87.1%, P = 1.000). However, persistent viremia during LPV/r monotherapy tended to be higher than during LPV/r with OBRs (10.3% versus 3.2%, P = .346). History of viral blip during virologic suppression with second-line PI-based regimen is a predictor of achieving viral suppression at all visits (adjusted relative risk 0.255 [95% confidence interval 0.080-0.821], P = .022). Use of LPV/r monotherapy as maintenance regimen in this study produced persistent viremia that tended to be higher than LPV/r monotherapy with OBRs.

ObjectiveTo assess the efficacy and safety of first-line treatment with once-daily saquinavir/ritonavir with two nucleoside reverse transcriptase inhibitors (NRTIs), as induction therapy before enrollment in a randomized trial of structured treatment interruption strategies.DesignTwo-hundred antiretroviral-naive patients with CD4+cell counts between 200–350 at screening were enrolled in this open-label 24week study.MethodsPatients were followed up every 8 weeks for CD4+cells, HIV RNA, and clinical and laboratory toxicities. Results: Two-hundred patients were enrolled with median baseline CD4+cell count of 267 cells/μl and HIV RNA 50 118 (4.7 log10) copies/ml. After 24 weeks of treatment, 191 of 200 (96%) patients had below 400 copies/ml HIV RNA, with 177/200 (89%) below 50 copies/ml (intent to treat, missing equals failure method), with a median rise in CD4+cell count of 122 cells/μl. There was no significant correlation between the minimum concentration of saquinavir and HIV RNA reductions at week 8 ( P=0.957) or absolute HIV RNA at week 24 ( P=0.77).ConclusionFirst-line highly active antiretroviral therapy (HAART) with once-daily saquinavir/ritonavir plus two NRTIs showed strong antiviral efficacy over 24 weeks, and should be evaluated in larger prospective randomized clinical trials.

Author(s): Chotivichien, S; Detels, R; Arab, L; Prasithsirikul, W; Manosuthi, W; Sinawat, S

Thai patients enrolled in STACCATO with HIV/hepatitis B virus (HBV) co-infection and tenofovir/emtricitabine-based antiretroviral therapy (ART) were randomly assigned to continuous treatment or CD4 cell count-guided interruptions. HBV replication was suppressed below detection in 15/16 patients. Structured treatment interruption increased transaminases and HBV viraemia in five of six patients; one flare was severe. Conversion to anti-hepatitis Be occurred with continuous treatment only. Tenofovir/emtricitabine-containing ART is highly effective in controlling chronic HIV/HBV co-infection but treatment should not be interrupted.

Seventy human immunodeficiency virus (HIV)-infected patients receiving rifampicin and 70 HIV-infected patients not receiving rifampicin were enrolled to receive 400 mg of nevirapine-based highly active antiretroviral therapy per day. Mean plasma nevirapine levels at 8 and 12 weeks were lower in patients receiving rifampicin (P=.048). However, virological and immunological outcomes at 24 weeks were not different between the 2 groups (P>.05).

The present study aimed to evaluate the role of genetic polymorphisms in the emergence of lipoatrophy or lipodystrophy in HIV-infected patients with antiretroviral therapy (ART) in Thailand. Position 455 upstream of the Apolipoprotein C3 gene (ApoC3 T–455C, rs2854116), codon 64 of the Beta3 adrenergic receptor gene (ARβ3 Tcod64C, rs4994), and position 670 upstream of the Fas gene (Fas A–670G, rs1800682) were genotyped in 829 HIV-infected Thai patients who had started ART. Crude and adjusted incidence rate ratios (IRR) were calculated using Poisson regression. The serum levels of cholesterol, triglycerides, high-density lipoprotein (HDL), and low-density lipoprotein (LDL) were also analyzed. Multivariate analysis revealed an association between the Fas −670AA genotype, but not the ApoC3 −455 or ARβ3 cod64 genotypes, with the incidence of lipoatrophy after adjusting for gender and stavudine (d4T)-containing regimens (IRR=1.72, 95% CI=1.20–2.45, p=0.003). However, ApoC3 −455C homozygous patients showed elevated serum levels of triglycerides, while this genotype did not affect serum total cholesterol, HDL, or LDL levels in patients with lipoatrophy or lipodystrophy. In contrast, the ARβ3 cod64 genotype did not show any significant association with the serum levels of cholesterol, triglycerides, HDL, or LDL. In conclusion, Fas −670AA affected the incidence of lipoatrophy in HIV-1-infected Thai patients, while the ApoC3 −455C allele affected the serum levels of triglycerides. These results confirmed the role of genetics in the development of ART-related metabolic disorders.

We compared rates of neurocognitive impairment (NCI) among 93 Thai adults failing non-nucleoside reverse transcriptase inhibitor (NNRTI)-based combination antiretroviral therapy (cART) before and after switching to lopinavir/ritonavir monotherapy (mLPV/r) vs. tenofovir/lamivudine/LPV/r (TDF/3TC/LPV/r). Participants completed the Color Trails 1 and 2, Digit Symbol, and Grooved Pegboard at weeks 0, 24, and 48. We calculated z-scores using normative data from 451 healthy HIV-negative Thais. We defined NCI as performance of

Skin and mucocutaneous disease changed its spectrum after Highly Active Antiretroviral Therapy (HAART) had been introduced. Previous publication showed opportunistic infections (OIs) related skin disease was a major presentation in pre-HAART era, whereas non-infected skin disease became emerging in HAART era. There is no report describing skin disease in HAART era among Thai HIV-infected patients.To describe the prevalence of skin and mucocutaneous disease in Thai HIV-infected patients after using HAART MATERIAL AND METHOD: A cross-sectional retrospective study analyzed skin diseases of 237 HIV-infected patients who were currently on HAART who attended the out-patient skin clinic at Bamrasnaradura Infectious Diseases Institute between September 1, and October 31, 2010. There were 312 lesions. The skin diseases were diagnosed by dermatologists and grouped into four groups as infectious skin disease, non-infectious inflammatory skin disease, tumor and miscellaneous group. Percentage was calculated in each of skin disease prevalence.The results showed 155 (65%) were men, and mean (SD) of age was 41 (8.8). Median (IQR) of CD4 count was 330 (178, 527) cell/mm3. The regimens of HAART in the population were 79% for NNRTI based, 20% for PI based, and 1% for tripled NRTI. The time between initial HAART and date of diagnosis of most patients (52%) was more than three years. Non-infected skin disease (61%) was the most common skin disorder prevalence, followed by infectious disease (31%), tumor (0.96%), miscellaneous (6.09), respectively. The most common skin disease was eczema (21%). Four subjects developed drug eruption, all from Efavirenz. Atypical presentation specifically to HIV patients as chronic hypertrophic erosive herpes genitalis (one of IRIS) was found in four patients (20% of all HSV infectious prevalence).Non-infectious inflammatory skin disease is the most common skin prevalence in HIV-infected patients after receiving HAART Eczema was the most diagnosed skin disease. There were skin diseases related to immune restoration after using HAART and from HAART itself but in low prevalence.

Background Data informing the use of boosted protease inhibitor (PI) monotherapy as second-line treatment are limited. There are also no randomized trials addressing treatment options after failing first-line non-nucleoside reverse transcriptase inhibitor (NNRTI)-regimens. Methods HIV-infected subjects ≥18 years, with HIV RNA≥1,000 copies/ml while using NNRTI plus 2 NRTIs, and naive to PIs were randomized to lopinavir/ritonavir (LPV/r) 400/100 mg twice daily monotherapy (mono-LPV/r) or tenofovir disoproxil fumarate (TDF) once daily plus lamivudine (3TC) twice daily plus LPV/r 400/100 mg twice daily (TDF/3TC/LPV/r) at nine sites in Thailand. The primary outcome was time-weighted area under curve (TWAUC) change in HIV RNA over 48 weeks. The a priori hypothesis was that the mono-LPV/r arm would be considered non-inferior if the upper 95% confidence limit in TWAUC mean difference was ≤0.5 log10 copies/ml. Results The intention-to-treat (ITT) population comprised 195 patients (mono-LPV/r n=98 and TDF/3TC/LPV/r n=97): male 58%, baseline mean (sd) age of 38 (7) years, CD4+ T-cell count of 204 (135) cells/mm3 and HIV RNA of 4.1 (0.6) log10 copies/ml. The majority had HIV-1 recombinant CRF01_AE infection, and thymidine analogue mutation (TAM)-2 was 3x more common than TAM-1. At 48 weeks, the difference in TWAUC HIV RNA between arms was 0.15 (95% CI -0.04, 0.33) log10 copies/ml, consistent with our definition of non-inferiority. However, the proportion with HIV RNA10 copies/ml ( PConclusions In PI-naive patients failing NNRTI-based first-line HAART, mono-LPV/r had a significantly lower proportion of patients with HIV RNA

The national health insurance fund in Thailand initiated by the national health security act in November, 2002. In October 2007, the national health insurance fund launched the first renal replacement therapy (RRT) reimbursement plan by the "Peritoneal Dialysis-First" (PD First) policy. The rationale of the PD First Policy resulted from the perspective that PD for end stage renal disease (ESRD) treatment offers the most economic and efficient outcome. The present study was conducted to determine whether the increase of RRT penetration by national health policy could impact the national RRT prevalence.The Thailand Renal Replacement Therapy (TRT) database in 2007, 2008, and 2009 were retrieved and analyzed.By TRT registry data, the total yearly prevalence of RRT increased by an average of 14.8% after the implementation of national health insurance and the "PD First" policy from 2007 to 2009. The total yearly prevalence of hemodialaysis (HD) modestly increased (14.7%) while the total yearly prevalence of PD remarkably expanded by 107.3%. The yearly incidence of all RRT modalities increased by an average of 34.8% in 2007 to 2009. The yearly incidence of HD modestly increased (8.1%) while the total yearly incidence of PD remarkably elevated by 157.8%. Civil Servants Medical Benefit Compensation (CSMBS) was the major funding source of RRT cases (34.5%) while national health insurance funding was the second major funding source (26.0%). From 2007-2009, the CSMBS funding was the majority of HD while national health insurance funding was the majority of PD. The sharing of PD by national health insurance increased from 33.9% in 2007, 58.6% in 2208, and 77.2% in 2009.The coverage ofESRD patients by national health insurance fund by the "PD First" policy impacted the RRT prevalence and incidence both the total prevalence and total incidence due to the universal penetration to RRT treatment of Thai population. Also, the policy altered the RRT modality predisposition. PD modality willfinally be the majority ofThaiRRT modalities if the policy can be managed successfully.

Background We studied prevalence of etravirine (ETR) and rilpivirine (RPV) resistance in HIV-1 subtype CRF01_AE infection with first-line non-nucleoside reverse transcriptase inhibitor (NNRTI) failure. Methods A total of 225 adults failing two nucleoside reverse transcriptase inhibitors (NRTIs) plus 1 NNRTI in Thailand with HIV RNA>1,000 copies/ml were included. Genotypic resistance results and HIV-1 subtype were interpreted by Stanford DR database. ETR resistance was calculated by the new Monogram weighted score (Monogram WS; ≥4 indicating high-level ETR resistance) and by DUET weighted score (DUET WS; 2.5–3.5 and ≥4 resulted in intermediate and reduce ETR response, respectively). RPV resistance interpretation was based on previous reports. Results Median (IQR) age was 38 (34–42) years, 41% were female and CDC A:B:C were 22%:21%:57%. HIV subtypes were 96% CRF01_AE and 4% B. Antiretrovirals at failure were lamivudine (100%), stavudine (93%), nevirapine (90%) and efavirenz (10%) with a median (IQR) duration of 3.4 (1.8–4.5) years. Median (IQR) CD4+ T-cell count and HIV RNA were 194 (121–280) cells/mm3 and 4.1 (3.6–4.6) log10 copies/ml, respectively. The common NNRTI mutations were Y181C (41%), G190A (22%) and K103N (19%). The proportion of patients with Monogram WS score ≥4 was 61.3%. By DUET WS, 49.8% and 7.5% of patients were scored 2.5–3.5 and ≥4, respectively. Only HIV RNA≥4 log10 copies/ml at failure was associated with both Monogram WS≥4 (OR 2.3, 95% CI 1.3–3.9; P=0.003) and DUET WS≥2.5 (OR 1.9, 95% CI 1.1–3.3; P=0.02). The RVP resistance-associated mutations (RAMs) detected were K101P (1.8%), Y181I (2.7%) and Y181V (3.6%). All patients with RPV mutation had ETR resistance. No E138R/E138K mutations were detected. Conclusions Approximately 60% of patients had high-level ETR resistance. The role of ETR in second-line therapy is limited in late NNRTI failure settings. RVP RAMs were uncommon, but cross-resistance between ETR and RVP was high.

A retrospective cohort study was conducted among HIV-1 infected patients taking tenofovir as part of an anti-HIV drug regimen in a resource-limited setting in Thailand. One hundred thirty patients with a mean_SD age of 39.7+/-7.4 years, of whom 55% were male, were included in the study. Fifty-eight (45%), 48 (37%), and 24 (18%) patients concurrently received nevirapine-based, efavirenz-based, and protease inhibitor (PI)-based regimens, respectively. The median (IQR) value for serum creatinine was 0.8 (0.6-0.9) mg/dl, for eGFR was 103 (96-120) ml/min/1.73 m2 and for CD4 was 302 (194-511) cells/mm3 at the time of tenofovir initiation. At 3-6 months, the median (IQR) eGFR was 100 (88-117) ml/min/1.73 m2 (p=0.002, compared to baseline). The proportions of patients with an estimated glomerular filtration rate (eGFR)30 ml/min/1.73 m2 at baseline and 3-6 months were 0% and 2%, respectively (p0.001). At 6-months follow-up, 2 patients (1.4%) were diagnosed with acute renal failure at 3 weeks and 9 weeks after tenofovir use, respectively. Both patients received a boosted PI in the regimen. Overall, the incidence of acute renal failure was 0.26 per 100 person-months. Renal function progressed to irreversible renal failure in one patient. In summary, tenofovir-associated renal impairment is not uncommon in a real-life practice. This report highlights the potentially irreversible adverse effect of this agent, particularly in patients with vulnerable kidneys and concomitant use of tenofovir and boosted PI.

To assess safety and tolerability of enfuvirtide, an antiretroviral, in Thai patients with advanced HIV-1 disease who have received antiretroviral treatment and failed on regimens that contain at least one of each antiretroviral (ARV) classes (PIs, NRTIs, and NNRTIs), or who have intolerance to previous antiretroviral regimens.An open-label non-comparative study of enfuvirtide used in salvage regimens along with the backbone antiretroviral therapy of choice in Thai HIV-1 experienced cases that have been treated with at least one of each available ARV classes.Twenty-three patients were recruited from five participating centers. Seventeen patients (74%) completed 96 weeks of the treatment. Six patients prematurely withdrew from the present study in which three expired from HIV related complications, two withdrew consents, and one from adverse event. The most common adverse event is injection site reactions, which occurred in 22 patients. The manifestations and intensity varied from rash, erythema, edema, pain, induration, and bleeding at the injection sites, to inflammatory nodules. Most of the patients tolerated the treatment well. Enfuvirtide administered along with other antiretroviral combination provided a good control of the disease.Enfuvirtide was well tolerated by Thai patients who participated in the present study. The adverse events did not compromise the patient compliance.

Background Different strategies of ritonavir-boosted lopinavir monotherapy have been explored; however, data regarding salvage therapy among HIV-infected patients who failed nucleoside reverse transcriptase inhibitor (NRTI) and non-nucleoside reverse transcriptase inhibitor (NNRTI) is still limited. Methods A prospective study was conducted among HIV-infected patients who failed NNRTI-based antiretroviral therapy with M184V, TAMs, and NNRTI mutations, and were naïve to protease inhibitor. LPV/r at 400/100 mg and lamivudine 150 mg were given twice daily. CD4 and HIV-1 RNA were monitored at week 0, 12, 24, and 48. LPV Cmin was assayed for the first 14 patients using HPLC. Results There were 40 patients with a mean age of 37 years and 70% were male. Median (IQR) baseline CD4 was 123 (37-245) cells/mm3 and median (IQR) HIV-1 RNA was 55,800 (9,670-100,000) copies/mL. By intend-to-treat analysis, 30 (75%) and 24 (60%) patients achieved HIV-1 RNA at 3 and significantly changed from baseline (all, P < 0.05). At 6 and 12 weeks, median (min-max) LPV Cmin was 6.52 (1.62-11.64) mg/L and 5.79 (0.75-16.31) mg/L, respectively. There were increments of mean total cholesterol and triglyceride at 48 weeks from baseline (P < 0.05). Conclusion LPV/r monotherapy with recycled lamivudine can maintain virological suppression in a substantial proportion of patients failing NNRTI-based regimen and provides adequate plasma concentrations of LPV although the incidence of low-level viremia is relatively high.