Occupational Post-exposure Prophylaxis after Blood and Body Fluids Exposure among Healthcare Workers in Siriraj Hospital

Objective: The present study aimed to describe the characteristics of occupational exposure to bloodborne pathogens and occupational post-exposure prophylaxis (oPEP) in Siriraj Hospital. Materials and Methods: A descriptive, retrospective cohort study was performed of healthcare workers (HCWs) who had experienced occupational injury in Siriraj Hospital in 2015. Data were extracted from the hospital database. Results: In total, 389 injury episodes were described; of which 293 (75.3%) involved female staff, and 112 (28.8%) involved nurses. The highest number of accidents (112, 28.8%) occurred in the operation room. Needlestick injury (210, 54%) was the most common injury. Overall, 94 (24.1%) HCWs received oPEP; 67 (71.2%) events carried a risk of HIV acquisition, and in 27 (28.7%) cases, the patients decided to take oPEP. Common oPEP regimens were TDF/XTC/LPV/r (33, 35.1%) and TDF/XTC/RPV (32, 34%). Nearly half of the HCWs who received an LPV/r-based oPEP regimen had gastrointestinal intolerance and switched to second-line regimens. Among those who received oPEP, 52 (77.6%) returned at 1 month and 26 (38.8%) returned at 3 months after exposure for a serology test. There was no seroconversion in this cohort. Conclusion: Occupational exposure to bloodborne pathogens is a common and increasing risk of infection among HCWs. oPEP with effective antiretroviral drugs within 72 hours after exposure is the main strategy for HIV prevention. The selection of an oPEP regimen with less toxic pills should be considered for efficacy, safety, and adherence. Interventions such as a tracking system or message reminders should be implemented to improve the follow-up rate among HCWs

Development of a Novel Method for Determination of 11 Antiretroviral Drugs Concentrations in Human Plasma by Ultra-Performance Liquid Chromato- graphy-Photodiode Array Detection Method

Objective: To develop ultra-performance liquid chromatography-photodiode array detection (UPLC-PDA) method that is fully validated for measuring 11 antiretroviral drugs concentrations in human plasma. Methods: Chromatographic separation was performed on an ACQUITY UPLCTM BEH Shield RP, 1.7 μm (100 mm x 2.1 mm I.D.) and used acetronitrile with 0.1% formic acid in Milli-Q water as a mobile phase. ACQUITY UPLC® Photodiode Array (PDA) Detector was performed at 210, 240, and 260 nm. Results: This method demonstrated a good separation result for plasma levels of 11 antiretroviral drugs within 16 minutes. The lower limit of quantification (LLOQ) was 0.25 μg/mL for maraviroc, 0.5 μg/mL for lopinavir, and 20 ng/mL for the remaining 9 antiretroviral drugs. This method was fully validated in terms of selectivity, accuracy, precision, and stability. The standard curves are in the expected ranges of drug concentration in the patients’ plasma with good linearity (r2>0.995). Recoveries of extraction ranged from 72.27- 110.80% with repeatability. Conclusion: A novel, sensitive, accurate, and reproducible UPLC/PDA method for quantification of 11 currently- prescribed antiretroviral drugs concentrations in human plasma was successfully developed and fully validated according to USFDA guidelines

Leptospirosis 2001

A 20-year-old man was admitted to Siriraj Hospital because of high fever and jaundice. He also had acute renal failure. According to the other clinical manifestations and laboratory investigations, the differential diagnosis included severe systemic infections, especially leptospirosis and scrub typhus. A definitive diagnosis was obtained by a positive microscopic agglutination test for Leptospira interrogans, serovar bratislava. Serological tests for scrub typhus and dengue infection were negative. The number of patients with leptospirosis has been increasing in many hospitals and outbreaks of the disease have been reported in northeastern Thailand since 1997. In October 1999, Leptospira interrogans, serovar pyrogenes was isolated from the blood of a febrile patient with clinical leptospirosis in Burium province. This pathogen was used to study the progressive microanatomical changes within organs including the kidney, lungs, liver, gastrocnemius and hamstring muscles of infected hamsters. The kidney showed degenerative changes of the renal tubular cells and many pathological appearances of the glomerular tuft. Interstitial nephritis and pyelonephritis were also found. In the lungs, the alveolar and interalveolar capillaries were engorged with red blood cells. Both bronchopneumonitis and interstitial pneumonitis were observed. The liver showed cloudy swelling of hepatocytes which lead to dissociation of the hepatic cords. Vascular and sinusoidal congestion, prominent Kupffer cells and inflammatory cell infiltration in the parenchyma, and sinusoids as well as the portal area were demonstrated. Hepatocellular necrosis was found scattered throughout the hepatic lobules. Some hamsters showed blood vessel congestion in the gastrocnemius and hamstring muscles. Inflammatory cell infiltration was shown in the perimysium of the gastrocnemius muscle of one hamster. Another showed necrosis of some muscle fibers together with inflammatory cell infiltration which are sings of muscular inflammation. The prevention and control of Leptospirosis is discussed

High Performance Liquid Chromatographic Assay for the Determination of Protease Inhibitors (PIs) and Non-nucleoside Reverse Transcriptase Inhibitors (NNRTIs) in Human Plasma

Objective: To develop and validate a high performance liquid chromatography (HPLC) method for simultaneous quantitative determination offive HIV protease inhibitors (PIs): indinavir (IDV), lopinavir (LPV), nelfinavir (NFV), ritonavir (RTV), saquinavir (SQV), andtwonon-nucleoside reverse transcriptase inhibitors (NNRTIs):nevirapine (NVP), andefavirenz (EFV) inhumanplasma. Methods: A sample of 200 µL of plasma and an internal standard were extracted with tert-butyl methyl ether. The compounds were separated on a reversed-phase C18 column with gradient phase of 25 mM phosphate buffer (pH 4.9) and acetonitrile. The limit of quantation, accuracy, precision, specificity, stability andrecovery were tested. Results: The lower limit of quantitation for all drugs was 75 ng/mL. The standard curve was linear in the range of 75 ng/mL to 20,000 ng/mL. Intra-day and inter-day variability ranged from 0.1% to 2.4% and 0.3% to 4.1%, respectively. Accuracy ranged from 98.4%-102.4% for three quality controls (75, 100, and 1,000 ng/mL) for all drugs measured. The extraction recovery ranged from 98.7%-101.3%. Conclusion: This method provides a simple, accurate, and precise method for monitoring of plasma concentrations of five PIs and two NNRTIs in the case of weak economy and out of date instrumental limitations

Adherence and Health Problems in Thai Travellers Living with HIV

It is important to focus on adherence to antiretroviral therapy (ART) and health problems of travellers living with HIV (TLWHIV) during travel. This study was conducted to investigate factors related to adherence and health problems among TLWHIV. This multicentre, cross-sectional observational study was conducted among TLWHIV in university hospitals from August 2019 to July 2020. Factors associated with adherence to ART were evaluated using a logistic regression model. Health problems and risk exposure were also examined among participants during travel. Of 321 TLWHIV, 20 (6.23%) showed moderate-to-poor adherence, among whom 3 (15%) had viral rebound after travelling. Travellers frequently missed ART during the first 3 days of their trip. International destination was associated with moderate-to-poor adherence. In total, 237 (73.8%) travellers reported health problems during travel, among whom 36 required medical attention. Sexual or sharp exposure was found in <5% of travellers during travel. Approximately 95% of Thai TLWHIV had good ART adherence. International destination was the major factor determining adherence. TLWHIV should be encouraged to seek pretravel consultation. Healthcare providers should discuss health risk prevention and teach about ART dosing during travel to enhance adherence and minimise toxicity

A Risk Prediction Model and Risk Score of SARS-CoV-2 Infection Following Healthcare-Related Exposure

Hospital workers are at high risk of contact with COVID-19 patients. Currently, there is no evidence-based, comprehensive risk assessment tool for healthcare-related exposure; so, we aimed to identify independent factors related to COVID-19 infection in hospital workers following workplace exposure(s) and construct a risk prediction model. We analyzed the COVID-19 contact tracing dataset from 15 July to 31 December 2021 using multiple logistic regression analysis, considering exposure details, demographics, and vaccination history. Of 7146 included exposures to confirmed COVID-19 patients, 229 (4.2%) had subsequently tested positive via RT-PCR. Independent risk factors for a positive test were having symptoms (adjusted odds ratio 4.94, 95%CI 3.83–6.39), participating in an unprotected aerosol-generating procedure (aOR 2.87, 1.66–4.96), duration of exposure >15 min (aOR 2.52, 1.82–3.49), personnel who did not wear a mask (aOR 2.49, 1.75–3.54), exposure to aerodigestive secretion (aOR 1.5, 1.03–2.17), index patient not wearing a mask (aOR 1.44, 1.01–2.07), and exposure distance <1 m without eye protection (aOR 1.39, 1.02–1.89). High-potency vaccines and high levels of education protected against infection. A risk model and scoring system with good discrimination power were built. Having symptoms, unprotected exposure, lower education level, and receiving low potency vaccines increased the risk of laboratory-confirmed COVID-19 following healthcare-related exposure events

Comparisons of Primary HIV-1 Drug Resistance between Recent and Chronic HIV-1 Infection within a Sub-Regional Cohort of Asian Patients.

BACKGROUND:The emergence and transmission of HIV-1 drug resistance (HIVDR) has raised concerns after rapid global antiretroviral therapy (ART) scale-up. There are limited data on the epidemiology of primary HIVDR in resource-limited settings in Asia. We aimed to determine the prevalence and compare the distribution of HIVDR in a cohort of ART-naïve Asian patients with recent and chronic HIV-1 infection. METHODS:Multicenter prospective study was conducted in ART-naïve patients between 2007 and 2010. Resistance-associated mutations (RAMs) were assessed using the World Health Organization 2009 list for surveillance of primary HIVDR. RESULTS:A total of 458 patients with recent and 1,340 patients with chronic HIV-1 infection were included in the analysis. The overall prevalence of primary HIVDR was 4.6%. Recently infected patients had a higher prevalence of primary HIVDR (6.1% vs. 4.0%, p = 0.065) and frequencies of RAMs to protease inhibitors (PIs; 3.9% vs. 1.0%, p<0.001). Among those with recent infection, the most common RAMs to nucleoside reverse transcriptase inhibitors (NRTIs) were M184I/V and T215D/E/F/I/S/Y (1.1%), to non-NRTIs was Y181C (1.3%), and to PIs was M46I (1.5%). Of patients with chronic infection, T215D/E/F/I/S/Y (0.8%; NRTI), Y181C (0.5%; non-NRTI), and M46I (0.4%; PI) were the most common RAMs. K70R (p = 0.016) and M46I (p = 0.026) were found more frequently among recently infected patients. In multivariate logistic regression analysis in patients with chronic infection, heterosexual contact as a risk factor for HIV-1 infection was less likely to be associated with primary HIVDR compared to other risk categories (odds ratio 0.34, 95% confidence interval 0.20-0.59, p<0.001). CONCLUSIONS:The prevalence of primary HIVDR was higher among patients with recent than chronic HIV-1 infection in our cohort, but of borderline statistical significance. Chronically infected patients with non-heterosexual risks for HIV were more likely to have primary HIVDR

Efficacy and safety of elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide in Asian participants with human immunodeficiency virus 1 infection: A sub-analysis of phase 3 clinical trials

Background: The efficacy and safety of a single tablet regimen (STR) of elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide (E/C/F/TAF) was analyzed in Phase 3 clinical trials in antiretroviral therapy (ART)-naive and ART-experienced Asian participants infected with human immunodeficiency virus (HIV)-1 through 96 or 144 weeks. Objective: In Asian population requiring treatment, it is imperative to have data specific to this group, particularly as there is a general concern that Asians with lower body weight have increased risk of tenofovir disoproxil fumarate (TDF)-related renal dysfunction. Methods: Studies -104 and 111 were randomized, double-blind, placebo-controlled, 144-week studies conducted in ART-naive participants, comparing E/C/F/TAF versus E/C/F/TDF. Study 109 was a randomized, open-label, 96-week study conducted in virologically suppressed, ART-experienced participants, who switched to E/C/F/TAF from ritonavir/cobicistat-boosted atazanavir ATV+(RTV or COBI) + F/TDF regimens, from non-nucleoside reverse transcriptase inhibitors (NNRTI) + F/TDF regimens, or from E/C/F/TDF. Study 112 was a single arm, open-label, 144-week study conducted in HIV suppressed, ART-experienced participants with mild-moderate renal impairment, who switched to E/C/F/TAF. Results: Asian participants in these studies had sustained efficacy safety and tolerability. In Study 104/111, Asian participants achieved 93% virologic suppression on TAF vs 88% on TDF at week 144. At baseline, there were numerically more Asians with median CD4 counts 100,000 c/mL. In Study 109, 95% of Asians on TAF vs 86% on TDF maintained virologic suppression at week 96. Lastly, in Study 112, 91% maintained virologic suppression at week 144. There were no discontinuations due to renal AE, no cases of PRT or Fanconi syndrome in any of the studies

Factors associated with primary HIV drug resistance by duration of HIV infection - univariate logistic regression.

<p><b>Abbreviations:</b> HBsAg – hepatitis B surface antigen, anti-HCV – antibody to hepatitis C virus.</p>*<p>p-value is for test for trend (excluding missing values) for age groups, CDC category, and HIV RNA.</p