Ploenchan Chetchotisakd
Khon Kaen University, Faculty of Medicine, Faculty Member
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Cefpirome is a fourth-generation cephalosporin with good activity against both gram-positive and gram-negative bacteria. A multicentre trial was performed to study the efficacy and safety of cefpirome 2 g twice daily in the treatment of... more
Cefpirome is a fourth-generation cephalosporin with good activity against both gram-positive and gram-negative bacteria. A multicentre trial was performed to study the efficacy and safety of cefpirome 2 g twice daily in the treatment of sepsis. Sixty-three cases were recruited from 10 hospitals from April 1996 to January 1998. Fifty seven cases could be evaluated according to the protocol. The APACHE II score was used to measure severity of illness, with 46.9 per cent of patients having APACHE II score more than 10 and two patients more than 20; both were cured. The most common pathogens were gram-negative bacteria with E. coli predominating 16/40 (40.0%), followed by Klebsiella 8/40 (20.0%). The overall clinical success rates were 54 out of 57 patients (94.7%). In patients with positive blood culture, the clinical cures were achieved for 20/22 (90.9%). Cefpirome showed good efficacy and safety in the empirical treatment of suspected bacteremia or sepsis.
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Raw LIPS data (LU) from separate tests for 8 MTB antigens with cohort 2. (XLS 18Â kb)
Characteristics of the cohorts used for LIPS testing. (PPT 79Â kb)
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bial Agents publishes original research articles, case reports and article reviews on various aspects of infectious diseases and antimicrobial agents. The contributions submitted to this journal should not be published else where in whole... more
bial Agents publishes original research articles, case reports and article reviews on various aspects of infectious diseases and antimicrobial agents. The contributions submitted to this journal should not be published else where in whole or in part, without the Editor’s permission. Accepted contributions become the copyright of Journal. Manuscripts should be accompanied by a covering letter from the author who is responsible for correspon-dence regarding the manuscript. The covering letter should contain a statement that the manuscript has been approved by all authors. A manuscript, tables and illustrations should be sent in duplicate together with a
Background There are few data on the selection of resistance by ritonavir-boosted saquinavir (SQV/r), particularly in antiretroviral (ARV)-naive patients. Objective To assess the incidence of virological failure and evolution of... more
Background There are few data on the selection of resistance by ritonavir-boosted saquinavir (SQV/r), particularly in antiretroviral (ARV)-naive patients. Objective To assess the incidence of virological failure and evolution of resistance in ARV-naive individuals receiving SQV/r in the induction phase of the Staccato trial. Methods ARV-naive subjects (n=272) received SQV/r 1,600/100 mg once daily with two nucleoside reverse transcriptase inhibitors (NRTIs) for at least 24 weeks. Patients were defined as having virological failure (VF) when there were two consecutive HIV-1 RNA measurements >500 copies/ml after week 12. Viral genotypes (reverse transcriptase [RT] and protease [PRO]) were determined at baseline in all patients and as close as possible to the time of initial failure in patients experiencing VF. Results VF was observed in 9/272 patients receiving SQV/r 1,600/100 mg once daily with two NRTIs (3.3%) and occurred 19–48 weeks after treatment initiation. Eight of these pa...
Research Interests: Microbiology, Medical Microbiology, Thailand, Medicine, HIV, and 15 moreHumans, Mutation, HIV protease, Female, Male, Clinical Sciences, Genotype, Adult, Highly Active Antiretroviral Therapy, Viral Load, ritonavir, Treatment Failure, Antiviral Therapy, reverse transcriptase inhibitors, and HIV infections
Background Treatment of melioidosis comprises intravenous drugs for at least 10 days, followed by oral trimethoprim-sulfamethoxazole (TMP-SMX) for 12 to 20 weeks. Oral TMP-SMX is recommended for 12 weeks in Australia and 20 weeks in... more
Background Treatment of melioidosis comprises intravenous drugs for at least 10 days, followed by oral trimethoprim-sulfamethoxazole (TMP-SMX) for 12 to 20 weeks. Oral TMP-SMX is recommended for 12 weeks in Australia and 20 weeks in Thailand. Methods For this open-label, pragmatic, multicenter, noninferiority, randomized controlled trial, we enrolled patients with culture-confirmed melioidosis who had received oral eradication treatment for 12 weeks and had no clinical evidence of active melioidosis. We randomly assigned patients to stop treatment (12-week regimen) or continue treatment for another 8 weeks (20-week regimen). The primary end point was culture-confirmed recurrent melioidosis within 1 year after enrollment. The noninferiority margin was a hazard ratio (HR) of 2.0. The secondary composite end point, combining overall recurrent melioidosis and mortality, was assessed post hoc. Results We enrolled 658 patients: 322 to the 12-week regimen and 336 to the 20-week regimen. Th...
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Research Interests: Medicine and Dolutegravir
Early clinical severity assessments during the 2009 influenza A H1N1 pandemic (pH1N1) overestimated clinical severity due to selection bias and other factors. We retrospectively investigated how to use data from the International Network... more
Early clinical severity assessments during the 2009 influenza A H1N1 pandemic (pH1N1) overestimated clinical severity due to selection bias and other factors. We retrospectively investigated how to use data from the International Network for Strategic Initiatives in Global HIV Trials, a global clinical influenza research network, to make more accurate case fatality ratio (CFR) estimates early in a future pandemic, an essential part of pandemic response. We estimated the CFR of medically attended influenza (CFRMA) as the product of probability of hospitalization given confirmed outpatient influenza and the probability of death given hospitalization with confirmed influenza for the pandemic (2009-2011) and post-pandemic (2012-2015) periods. We used literature survey results on health-seeking behavior to convert that estimate to CFR among all infected persons (CFRAR). During the pandemic period, 5.0% (3.1%-6.9%) of 561 pH1N1-positive outpatients were hospitalized. Of 282 pH1N1-positive...
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There is an urgent need for a simple and accurate test for the diagnosis of human Mycobacterium tuberculosis, the infectious agent causing tuberculosis (TB). Here we describe a serological test based on light emitting recombinant proteins... more
There is an urgent need for a simple and accurate test for the diagnosis of human Mycobacterium tuberculosis, the infectious agent causing tuberculosis (TB). Here we describe a serological test based on light emitting recombinant proteins for the diagnosis of pulmonary Mycobacterium tuberculosis infection. Luciferase Immunoprecipitation Systems (LIPS), a fluid-phase immunoassay, was used to examine antibody responses against a panel of 24 different M. tuberculosis proteins. Three different strategies were used for generating the constructs expressing the recombinant fusion M. tuberculosis proteins with luciferase: synthetic gene synthesis, Gateway recombination cloning, and custom PCR synthesis. A pilot cohort of African pulmonary TB patients was used for initial antibody screening and confirmatory studies with selected antigens were performed with a cohort from Thailand and healthy US blood donors. In addition to testing M. tuberculosis antigens separately, a mixture that tested se...
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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... more
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 [CI] 1.19–8.34) and being educated to primary school level or less (OR 2.24; 95% CI 1.01–4.94) were associated with self-reported adherence <95% on the VAS in mu...
Research Interests: Behavior, Medical Microbiology, Medication Adherence, Developing Countries, Thailand, and 15 moreHealth, Medicine, Therapeutic drug monitoring, Antiretroviral Therapy, Humans, Female, Male, Clinical Sciences, Middle Aged, Adult, Clients, Public health systems and services research, Highly Active Antiretroviral Therapy, Sensitivity and Specificity, and HIV infections
The aim of this study was to identify baseline prognostic factors for poor clinical outcome of HIV-associated cryptococcal meningitis. We conducted a trial in Thailand and the USA comparing low- and high-dose concomitant use of... more
The aim of this study was to identify baseline prognostic factors for poor clinical outcome of HIV-associated cryptococcal meningitis. We conducted a trial in Thailand and the USA comparing low- and high-dose concomitant use of amphotericin B and fluconazole for HIV-associated cryptococcal meningitis to amphotericin B followed by fluconazole. Subjects who were either alive and cerebrospinal fluid (CSF) culture-positive or dead were considered to have a poor outcome. At day 14, baseline characteristics associated with poor outcome included: low weight, high CSF cryptococcal antigen (CrAg) titre and low CSF white blood cell (WBC) count. At day 70, the associated baseline characteristics included: CSF CrAg titre >1:1024 and low Karnofsky performance status. Overall, consistent with published findings, low weight, high CSF CrAg titre and low CSF WBC counts at baseline were predictors for poor clinical outcome. In addition, we found that low Karnofsky performance status was predictive...
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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... more
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%) w...
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... Dr Graeme Meintjies is supported by the Wellcome Trust. ... 4. Lehloenya R, Meintjes G. Dermatologic manifestations of the immune reconstitution inflammatory syndrome. Dermatol Clin 2006; 24:549-570. ... Bunning RD, Werner FB.... more
... Dr Graeme Meintjies is supported by the Wellcome Trust. ... 4. Lehloenya R, Meintjes G. Dermatologic manifestations of the immune reconstitution inflammatory syndrome. Dermatol Clin 2006; 24:549-570. ... Bunning RD, Werner FB. Cryptococcal arthritis and cellulitis. ...
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Melioidosis is an often fatal infection in tropical regions caused by an environmental bacterium, Burkholderia pseudomallei. Current recommended melioidosis treatment requires intravenous β-lactam antibiotics such as ceftazidime (CAZ),... more
Melioidosis is an often fatal infection in tropical regions caused by an environmental bacterium, Burkholderia pseudomallei. Current recommended melioidosis treatment requires intravenous β-lactam antibiotics such as ceftazidime (CAZ), meropenem (MEM), or amoxicillin-clavulanic acid (AMC) and oral trimethoprim-sulfamethoxazole. ABSTRACT Melioidosis is an often fatal infection in tropical regions caused by an environmental bacterium, Burkholderia pseudomallei. Current recommended melioidosis treatment requires intravenous β-lactam antibiotics such as ceftazidime (CAZ), meropenem (MEM), or amoxicillin-clavulanic acid (AMC) and oral trimethoprim-sulfamethoxazole. Emerging antibiotic resistance could lead to therapy failure and high mortality. We performed a prospective multicenter study in northeast Thailand from 2015 to 2018 to evaluate antibiotic susceptibility and characterize β-lactam resistance in clinical B. pseudomallei isolates. A collection of 1,317 B. pseudomallei isolates fr...
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Somnuek Sungkanuparph, Scott G. Filler, Ploenchan Chetchotisakd, Peter G. Pappas, Tracy L. Nolen, Weerawat Manosuthi, Thanomsak Anekthananon, Michele I. Morris, Khuanchai Supparatpinyo, Heather Kopetskie, Amy S. Kendrick, Philip C.... more
Somnuek Sungkanuparph, Scott G. Filler, Ploenchan Chetchotisakd, Peter G. Pappas, Tracy L. Nolen, Weerawat Manosuthi, Thanomsak Anekthananon, Michele I. Morris, Khuanchai Supparatpinyo, Heather Kopetskie, Amy S. Kendrick, Philip C. Johnson, Jack D. Sobel, and Robert A. Larsen Faculty of Medicine Ramathibodi Hospital, and Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Faculty of Medicine, Khon Kaen University, Khon Kaen, Department of Medicine, Bamrasnaradura Infectious Diseases Institute, Nonthaburi, and Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand; Los Angeles Biomedical Research Institute at Harbor–University of California at Los Angeles Medical Center, Torrance, and Faculty of Medicine, University of Southern California, Los Angeles; University of Miami Miller School of Medicine, Miami, Florida; University of Alabama at Birmingham Medical Center, Birmingham; University of Texas Houston Medical School, Houston; Wayne State University, Detroi...
Mycobacterium abscessus (Mab) is one of the most drug resistant bacteria with a high treatment failure rate. Antimicrobial peptides (AMPs) are alternative therapeutic agents against this infection. This study was aimed to assess the in... more
Mycobacterium abscessus (Mab) is one of the most drug resistant bacteria with a high treatment failure rate. Antimicrobial peptides (AMPs) are alternative therapeutic agents against this infection. This study was aimed to assess the in vitro activities of thirteen AMPs (S5, S52, S6, S61, S62, S63, KLK, KLK1, KLK2, Pug-1, Pug-2, Pug-3 and Pug-4) that have never been investigated against drug resistant Mab isolates. Only four novel modified AMPs (S61, S62, S63 and KLK1) provided the lowest minimum inhibitory concentration (MIC) values ranging from 200–400 μg/ml against the Mab ATCC19977 strain. These four potential AMPs were further tested with 16 clinical isolates of clarithromycin resistant Mab. The majority of the tested strains (10/16 isolates, 62.5%) showed ~99% kill by all four AMPs within 24 hours with an MIC <50 μg/ml. Only two isolates (12.5%) with acquired clarithromycin resistance, however, exhibited values <50 μg/ml of four potential AMPs, S61, S62, S63 and KLK1 afte...
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The anti-interferon-gamma (IFN-gamma) autoantibody is a known cause of opportunistic non-tuberculous mycobacterial (NTM) infection in adults. Diagnosis of those patients is difficult due to the low sensitivity of bacterial culture, and... more
The anti-interferon-gamma (IFN-gamma) autoantibody is a known cause of opportunistic non-tuberculous mycobacterial (NTM) infection in adults. Diagnosis of those patients is difficult due to the low sensitivity of bacterial culture, and because detection of the neutralizing autoantibody needs special laboratory devices. We conducted a retrospective review of indirect and inhibitory ELISA, both used for detection of anti-IFN-gamma auto-antibody in 102 patients with lymphadenopathies. We assessed hospital records of NTM isolation and/or diagnosis of NTM infection. The review revealed the compatible sensitivity and superior specificity and predictive values for inhibitory ELISA over against indirect ELISA—the latter achieving 100% specificity and positive predictive value for diagnosis of NTM infection in patients with lymphadenopathies. The results confirm functional assays that show plasma samples from NTM-infected patients with positive results by either indirect and/or inhibitory EL...
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Aim: To evaluate the influence of genetic polymorphisms on plasma trough concentrations of atazanavir (ATV) and ritonavir (RTV). Patients & methods: The concentration-to-dose ratios were compared between different genotype groups of... more
Aim: To evaluate the influence of genetic polymorphisms on plasma trough concentrations of atazanavir (ATV) and ritonavir (RTV). Patients & methods: The concentration-to-dose ratios were compared between different genotype groups of CYP3A5, ABCB1, SLCO1B1 and NR1I2 in 490 patients. Multiple regression analysis was used to examine the association between genetic and clinical factors and log-transformed concentration-to-dose ratio of ATV and RTV. Results: Higher concentrations of ATV and RTV were significantly associated with CYP3A5 6986 GG and SLCO1B1 521 TC or CC. Female patients had significantly higher ATV plasma concentration than male patients. Conclusion: Genetic polymorphisms and gender are factors affecting the variability of ATV and RTV concentrations in the Thai population. Thus, genetic testing is worth considering when atazanavir + low dose ritonavir is prescribed.
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Nontuberculous mycobacterial (NTM) infection is increasing worldwide. Current epidemiological data and knowledge of risk factors for this disease are limited. We investigated the trends in and risk of NTM infection in Northeast Thailand... more
Nontuberculous mycobacterial (NTM) infection is increasing worldwide. Current epidemiological data and knowledge of risk factors for this disease are limited. We investigated the trends in and risk of NTM infection in Northeast Thailand during 2012-2016. Patient demographics, infection site(s), and underlying disease or conditions from 530 suspected cases of NTM infections were retrieved from medical records, reviewed and analyzed. A diagnosis of true NTM infection was accepted in 150 cases. Risk factor analyses were done for extrapulmonary NTM infections compared to pulmonary NTM infections and for compared to members of the complex (MAC). Trend analysis among NTM species causing NTM infections was performed. The most common species of NTMs causing extrapulmonary ( = 114) and pulmonary ( = 36) NTM infections in Northeast Thailand were (25.4% of extrapulmonary infected cases and 27.8% of pulmonary cases) followed by MAC (14.9% of extrapulmonary and 13.9% of pulmonary cases). Presenc...
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Isavuconazole was compared to caspofungin followed by oral voriconazole in a phase 3, randomized, double-blind, multinational clinical trial (ACTIVE; NCT00413218) for primary treatment of patients with candidemia or invasive candidiasis.... more
Isavuconazole was compared to caspofungin followed by oral voriconazole in a phase 3, randomized, double-blind, multinational clinical trial (ACTIVE; NCT00413218) for primary treatment of patients with candidemia or invasive candidiasis. Adult patients were randomized 1:1 to isavuconazole (200 mg IV TID for 2 days, followed by 200 mg IV QD) or caspofungin (70 mg IV QD on day 1, followed by 50 mg IV QD [70 mg in patients >80 kg]) for a maximum of 56 days. After day 10, patients could switch to oral isavuconazole (isavuconazole arm) or voriconazole (caspofungin arm). The primary efficacy endpoint was successful overall response at end of IV therapy (EOIVT) in patients with proven infection who received ≥1 dose of study drug (modified-intent-to-treat [mITT] population). The pre-specified noninferiority margin was 15%. Secondary outcomes (mITT) were successful overall response at 2 weeks after end of treatment, all-cause mortality at days 14 and 56, and safety. Of 450 patients random...
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Ocular involvement in melioidosis is rare and has devastating outcomes. Although there have been few reports on the condition, Khon Kaen, a city in northeast Thailand, has been called the "capital of melioidosis" due to the high... more
Ocular involvement in melioidosis is rare and has devastating outcomes. Although there have been few reports on the condition, Khon Kaen, a city in northeast Thailand, has been called the "capital of melioidosis" due to the high prevalence of the condition in the region. We retrospectively reviewed all admitted cases of melioidosis with ocular involvement from the two largest hospitals in Khon Kaen. We reviewed cases from Srinagarind Hospital (a university hospital) of patients admitted between 1993 and 2016 and from Khon Kaen Hospital (a provincial hospital) of patients who presented from 2012 to 2016. We identified 16 cases of ocular involvement. Eight of these cases were proven from positive culture, and the remaining eight were implied from high melioidosis titer. The prevalence was estimated as being from 0.49 to 1.02%. Most patients had underlying diseases (14, 88%), of which diabetes mellitus was the most prevalent (12, 75%). Nine cases (56%) were part of disseminat...
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Excellent adherence to combination antiretroviral therapy can suppress HIV replication and produce life expectancies nearing those of individuals without HIV infection. This qualitative study sought to identify the barriers and... more
Excellent adherence to combination antiretroviral therapy can suppress HIV replication and produce life expectancies nearing those of individuals without HIV infection. This qualitative study sought to identify the barriers and facilitators to good antiretroviral medication adherence in Thai patients living with HIV. Semi-structured interviews were conducted with a convenience sample (n=21) of patients attending routine clinic visits at Srinagarind Hospital in Khon Kaen, or HIV-NAT, the Thai Red Cross AIDS Research Centre in Bangkok. Median informant age was 43 years (range 27-60 years) and 43% were female. We identified key facilitators and barriers to adherence among HIV-infected Thai patients along three major themes (patient-related, health system-related and medication-related). Stigma was a primary concern for most informants, operating throughout Thai society to induce feelings of shame for Thai people living with HIV. Determination to stay healthy and incorporate taking cART...
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Research Interests: Biomarkers, Survival Analysis, Medicine, Prospective studies, Humans, and 15 moreDiabetes mellitus, Female, Male, Staphylococcus aureus, Sepsis, Aged, Middle Aged, Prognosis, Disseminated Intravascular Coagulation, Fluid Therapy, Intensive Care Units, Disease Management, Interleukin, Respiratory insufficiency, and Medical and Health Sciences
Body composition and metabolic outcomes after 96 weeks of treatment with ritonavir-boosted lopinavir plus either nucleoside or nucleotide reverse transcriptase inhibitors or raltegravir in patients with HIV with virological failure of a standard first-line antiretroviral therapy regimen: a substu...more
Lipoatrophy is one of the most feared complications associated with the use of nucleoside or nucleotide reverse transcriptase inhibitors (N[t]RTIs). We aimed to assess soft-tissue changes in participants with HIV who had virological... more
Lipoatrophy is one of the most feared complications associated with the use of nucleoside or nucleotide reverse transcriptase inhibitors (N[t]RTIs). We aimed to assess soft-tissue changes in participants with HIV who had virological failure of a first-line antiretroviral (ART) regimen containing a non-nucleoside reverse transcriptase inhibitor plus two N(t)RTIs and were randomly assigned to receive a second-line regimen containing a boosted protease inhibitor given with either N(t)RTIs or raltegravir. Of the 37 sites that participated in the randomised, open-label, non-inferiority SECOND-LINE study, eight sites from five countries (Argentina, India, Malaysia, South Africa, and Thailand) participated in the body composition substudy. All sites had a dual energy x-ray absorptiometry (DXA) scanner and all participants enrolled in SECOND-LINE were eligible for inclusion in the substudy. Participants were randomly assigned (1:1), via a computer-generated allocation schedule, to receive either ritonavir-boosted lopinavir plus raltegravir (raltegravir group) or ritonavir-boosted lopinavir plus two or three N(t)RTIs (N[t]RTI group). Randomisation was stratified by site and screening HIV-1 RNA. Participants and investigators were not masked to group assignment, but allocation was concealed until after interventions were assigned. DXA scans were done at weeks 0, 48, and 96. The primary endpoint was mean percentage and absolute change in peripheral limb fat from baseline to week 96. We did intention-to-treat analyses of available data. This substudy is registered with ClinicalTrials.gov, number NCT01513122. Between Aug 1, 2010, and July 10, 2011, we recruited 211 participants into the substudy. The intention-to-treat population comprised 102 participants in the N(t)RTI group and 108 participants in the raltegravir group, of whom 91 and 105 participants, respectively, reached 96 weeks. Mean percentage change in limb fat from baseline to week 96 was 16·8% (SD 32·6) in the N(t)RTI group and 28·0% (37·6) in the raltegravir group (mean difference 10·2%, 95% CI 0·1-20·4; p=0·048). Mean absolute change was 1·04 kg (SD 2·29) in the N(t)RTI group and 1·81 kg (2·50) in the raltegravir group (mean difference 0·6, 95% CI -0·1 to 1·3; p=0·10). Our findings suggest that for people with virological failure of a first-line regimen containing efavirenz plus tenofovir and lamivudine or emtricitabine, the WHO-recommended switch to a ritonavir-boosted protease inhibitor plus zidovudine (a thymidine analogue nucleoside reverse transcriptase inhibitor) and lamivudine might come at the cost of peripheral lipoatrophy. Further study could help to define specific groups of people who might benefit from a switch to an N(t)RTI-sparing second-line ART regimen. The Kirby Institute and the Australian National Health and Medical Research Council.
Research Interests: International Cooperation, HIV, Humans, Female, Body Composition, and 13 moreMale, Adult, Highly Active Antiretroviral Therapy, Combination drug therapy, Lamivudine, Tenofovir, Emtricitabine, Raltegravir Potassium, Viral Load, ritonavir, Lopinavir, reverse transcriptase inhibitors, and HIV infections
Background Both human immunodeficiency virus (HIV) infection and antiretroviral therapy (ART) may increase cardiovascular disease (CVD) risk. Vascular function assessments can be used to study CVD pathogenesis. We compared the effect of... more
Background Both human immunodeficiency virus (HIV) infection and antiretroviral therapy (ART) may increase cardiovascular disease (CVD) risk. Vascular function assessments can be used to study CVD pathogenesis. We compared the effect of immediate versus deferred ART initiation at CD4 counts >500 cells/mm3 on small arterial elasticity (SAE) and large artery elasticity (LAE). Methods Radial artery blood pressure waveforms were recorded noninvasively. Small arterial elasticity and LAE were derived from analysis of the diastolic pulse waveform. Randomized treatment groups were compared with linear models at each visit and longitudinal mixed models. Results Study visits involved 332 participants in 8 countries: mean (standard deviation [SD]) age 35 (10), 70% male, 66% nonwhite, 30% smokers, and median CD4 count 625 cells/mm3 and 10-year Framingham risk score for CVD 1.7%. Mean (SD) SAE and LAE values at baseline were 7.3 (2.9) mL/mmHg × 100 and 16.6 (4.1) mL/mmHg × 10, respectively. M...
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We investigate mutations and correlates according to HIV-1 subtype after virological failure of standard first-line antiretroviral therapy (ART) (non-nucleoside/nucleotide reverse transcriptase inhibitor (NNRTI) + 2 nucleoside/nucleotide... more
We investigate mutations and correlates according to HIV-1 subtype after virological failure of standard first-line antiretroviral therapy (ART) (non-nucleoside/nucleotide reverse transcriptase inhibitor (NNRTI) + 2 nucleoside/nucleotide reverse transcriptase inhibitor (N(t)RTI). SECOND-LINE study participants were assessed at baseline for HIV-1 subtype, demographics, HIV-1 history, ART exposure, viral load (VL), CD4+ count and genotypic ART resistance. We used backwards stepwise multivariate regression (MVA) to assess associations between baseline variables and presence of ≥3N(t)RTI mutations, ≥1NNRTI mutation, ≥3thymidine-analogue N(t)RTI (ta-N(t)RTI) mutations (TAMs), the K65/K70 mutation, and predicted etravirine(ETV)/rilpivirine(RPV) activity. Inclusion p-value for MVA was p<0.2. Exclusion p-value from stepwise elimination was p>0.05. Of 541 participants, 491(91%) had successfully characterised baseline viral isolates. Subtype distribution: B (n=123, 25%), C (n=202, 41%),...
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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... more
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. 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. 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&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;0·0001). 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. The National Health Security Office and Kirby Institute for Infection and Immunity in Society.
Research Interests: Thailand, Adolescent, HIV, Pregnancy, Humans, and 7 moreFemale, Male, Young Adult, Adult, Viral Load, ritonavir, and HIV infections
Five blaOXA-48-like-carrying Enterobacteriaceae isolates collected from two Thai patients in December 2012 were characterized. Three Klebsiella pneumoniae isolates giving two different pulsed-field gel electrophoresis patterns and... more
Five blaOXA-48-like-carrying Enterobacteriaceae isolates collected from two Thai patients in December 2012 were characterized. Three Klebsiella pneumoniae isolates giving two different pulsed-field gel electrophoresis patterns and sequence types (ST11 and ST37) from patient 1 harbored blaOXA-48 locating on Tn1999.2, whereas two Escherichia coli isolates with the same pulsotype and ST5 from Patient 2 carried ISEcp1-associated blaOXA-181. One K. pneumoniae strain had blaSHV-12, blaDHA-1, qnrB, and qnrS, while another strain harbored blaCTX-M-15, qnrS and aac(6&amp;amp;#39;)-Ib-cr. The E. coli strain contained blaCTX-M-15, blaCMY-2, qnrS, and aac(6&amp;amp;#39;)-Ib-cr. Interestingly, the OXA-48 producers with a novel OmpK36 variant by a substitution of Gly to Asp in the L3 loop-borne PEFXG motif exhibited high-level resistance to ertapenem, imipenem, and meropenem. In contrast, the OXA-181 producer with non-porin-deficient background showed low-level resistance to ertapenem only. Both patients died because of either septic shock or pneumonia. This study showed the impact of OXA-48-like carbapenemases in porin-defective clinical isolate background, which may lead to serious therapeutic problems in the near future.
Research Interests: Microbiology, Medical Microbiology, Thailand, Molecular typing, Humans, and 15 moreEscherichia coli, Female, Male, Young Adult, Clinical Sciences, Middle Aged, Anti-Bacterial Agents, Genotype, Carbapenems, Pulsed field gel electrophoresis (PFGE), Escherichia Coli Infections, Beta Lactamases, Klebsiella pneumoniae, beta-Lactam Resistance, and Fatal outcome
To compare the efficacy and safety of 1,400 mg BID and 1,200 mg TID of saquinavir soft gel given with zidovudine and lamivudine in antiretroviral-naïve, advanced AIDS patients. A randomized, open-label study conducted at a university... more
To compare the efficacy and safety of 1,400 mg BID and 1,200 mg TID of saquinavir soft gel given with zidovudine and lamivudine in antiretroviral-naïve, advanced AIDS patients. A randomized, open-label study conducted at a university hospital. Forty cases were enrolled in the study, 20 cases in each group. The mean CD4 cell count was 29 cells/mm3. The mean log10 HIV-1 RNA was 5.27 copies/mL. Using an on-treatment analysis, the reduction in plasma log10HIV-1 RNA of BID and TID groups was not statistically significant at -2.44 vs -2.60 copies/mL (-0.16, 95% CI -0.63 to 0.30; p= 0.48). The mean increase in CD4 cell counts was not statistically significant at +144 and +159 cells/mm3 (11, 95% CI -75 to 97; p=0.79). The preliminary data suggests that in antiretroviral-naïve, advanced AIDS patients, 1,400 mg BID of saquinavir soft gel given with two nucleoside analogues might be as effective as the standard 1,200 mg TID.
Research Interests:
Research Interests:
Mucormycosis is an uncommon invasive fungal disease with high mortality and few treatment options. Isavuconazole is a triazole active in vitro and in animal models against moulds of the order Mucorales. We assessed the efficacy and safety... more
Mucormycosis is an uncommon invasive fungal disease with high mortality and few treatment options. Isavuconazole is a triazole active in vitro and in animal models against moulds of the order Mucorales. We assessed the efficacy and safety of isavuconazole for treatment of mucormycosis and compared its efficacy with amphotericin B in a matched case-control analysis. In a single-arm open-label trial (VITAL study), adult patients (≥18 years) with invasive fungal disease caused by rare fungi, including mucormycosis, were recruited from 34 centres worldwide. Patients were given isavuconazole 200 mg (as its intravenous or oral water-soluble prodrug, isavuconazonium sulfate) three times daily for six doses, followed by 200 mg/day until invasive fungal disease resolution, failure, or for 180 days or more. The primary endpoint was independent data review committee-determined overall response-ie, complete or partial response (treatment success) or stable or progressive disease (treatment fail...
Research Interests:
Research Interests:
Rilpivirine (RPV) is a non-nucleoside reverse transcriptase inhibitor, which has better lipid profiles than efavirenz (EFV) in treatment naïve patients. However, the data on treatment experience are limited especially in dyslipidemic HIV... more
Rilpivirine (RPV) is a non-nucleoside reverse transcriptase inhibitor, which has better lipid profiles than efavirenz (EFV) in treatment naïve patients. However, the data on treatment experience are limited especially in dyslipidemic HIV patients; thus, we aimed to assess the change of lipid profiles after switching from EFV to RPV in these patients. In this prospective, open-label, cohort study, we enrolled HIV-1 infected adults who had received at least 6 months of EFV-based regimen, with HIV RNA &amp;amp;amp;amp;lt;50 copies/mL for ≥6 months prior to switching. The objectives of this study were to analyze lipid changes and to evaluate the efficacy, safety, tolerability at 24 weeks after switching therapy. Fifty-three patients were enrolled and completed the study. At week 24, a significant decrease in the mean (95% confident interval, CI) total cholesterol (-28.06 mg/dL, 95%CI -35.20 to -20.91, p &amp;amp;amp;amp;lt; 0.0001), LDL-cholesterol (-20.96 mg/dL, 95%CI -28.12 to -13.80, p &amp;amp;amp;amp;lt; 0.0001), high-density lipoprotein (HDL)-cholesterol (-5.11 mg/dL, 95%CI -7.79 to -2.44, p &amp;amp;amp;amp;lt; 0.0001), and triglyceride (-29.79 mg/dL. 95%CI -52.39 to -7.19, p = 0.011) levels were observed. One patient had virologic rebound with HIV RNA of 114 copies/mL at week 24. Three (5.7%) patients had grade 2 elevations of liver enzymes. None of the patients discontinued RPV during the study. Switching from EFV-based therapy to RPV-based regimen improved lipid profiles in fully suppressed HIV patients with dyslipidemia. This treatment should be considered in these patients.