Search

Liver disease is a growing burden among people living with HIV (PLHIV) in resource-limited settings. As an indicator of liver disease, risk factors of high alanine aminotransferase (ALT) and cirrhosis were assessed among PLHIV in the TREAT Asia HIV Observational Database (TAHOD). Patients on combination antiretroviral therapy (cART) with a pre-cART ALT measurement and at least one follow-up ALT measurement were included. Factors associated with high ALT (ALT levels 5 times its upper limit of normal) were analyzed using repeated measure logistic regression over a 10-year follow-up period. Liver cirrhosis was defined as having an AST to Platelet Ratio Index score 1.5, fibrosis-4 score 3.25, or a clinical diagnosis of cirrhosis. Cox regression analysis stratified by site was used to analyze factors associated with cirrhosis among those in follow-up after 2015. Of 5182 patients, 101 patients (1.9%) had high ALT levels with hepatitis C virus (HCV) antibody positive (odds ratio [OR]: 4.98, 95% confidence interval [CI]: 2.82-8.77, p 0.001) and ever high alcohol consumption (OR: 2.33, 95% CI: 1.00-5.46, p = 0.050) as likely factors. Among 6318 PLHIV in the liver cirrhosis analysis, 151 (2%) developed cirrhosis (incidence rate = 0.82 per 100 person-years). Those HCV-antibody positive (hazard ratio [HR]: 5.54, 95% CI: 3.75-8.18, p 0.001) and had high alcohol consumption (HR: 2.06, 95% CI: 1.23-3.45, p = 0.006) were associated with liver cirrhosis. HCV-antibody positive and high alcohol consumption are factors associated with high ALT. With raised ALT levels as a known factor associated with liver cirrhosis, greater efforts are required in managing ALT levels and reducing the risk of developing liver cirrhosis among those positive for HCV-antibody and those who consume alcohol.

Worldwide, the ESKAPE group of pathogens - Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa and Enterobacter species - are emerging as important pathogens which have acquired resistance towards different classes of antibiotics. Malaysia has also reported high levels of antibiotic resistance among these pathogens, based on prevalence data from hospital patients. However, the prevalence and antibiotic resistance rates of ESKAPE group members in the community are largely unknown. Therefore, this study focuses on acute pharyngitis (AP) patients from private primary care clinics in the Klang Valley, central Malaysia, as AP is the most common infection-associated reason for contact with private primary healthcare providers. Out of 205 patients, 119 were found to harbor ESKAPE group bacteria, where a total of 175 isolates were subjected to antibiotic susceptibility testing. Our results show that the most prevalent ESKAPE group member in this cohort is S. aureus, with one isolate found to be multidrug-resistant towards penicillin V, cefoxitin, erythromycin and azithromycin. We also report the first finding of community acquired resistance to cefotaxime in K. pneumoniae, imipenem in Enterobacter spp. and tetracycline, also in Enterobacter spp., in Malaysia, which were not derived from samples from a hospital setting. In conclusion, this study, which describes antibiotic resistance of community acquired ESKAPE pathogens in the Malaysian private primary healthcare setting highlights the need for a comprehensive centralized reporting system for community acquired antibiotic resistance to complement the Malaysian National Surveillance of Antibiotic Resistance.

Mycobacterium avium complex prophylaxis is recommended for patients with advanced HIV infection. With the decrease in incidence of disseminated Mycobacterium avium complex infection and the availability of antiretroviral therapy (ART), the benefits of macrolide prophylaxis were investigated. This study examined the impact of macrolide prophylaxis on AIDS-defining conditions and HIV-associated mortality in a cohort of HIV-infected patients on ART.Patients from TREAT Asia HIV Observational Database (September 2015 data transfer) aged 18 years and older with a CD4 count50 cells/mm at ART initiation were included. The effect of macrolide prophylaxis on HIV-associated mortality or AIDS-defining conditions (as a combined outcome) and HIV-associated mortality alone were evaluated using competing risk regression. Sensitivity analysis was conducted in patients with a CD4100 cells/mm at ART initiation.Of 1345 eligible patients, 10.6% received macrolide prophylaxis. The rate of the combined outcome was 7.35 [95% confidence interval (CI): 6.04 to 8.95] per 100 patient-years, whereas the rate of HIV-associated mortality was 3.14 (95% CI: 2.35 to 4.19) per 100 patient-years. Macrolide use was associated with a significantly decreased risk of HIV-associated mortality (hazard ratio 0.10, 95% CI: 0.01 to 0.80, P = 0.031) but not with the combined outcome (hazard ratio 0.86, 95% CI: 0.32 to 2.229, P = 0.764). Sensitivity analyses showed consistent results among patients with a CD4100 cells/mm at ART initiation.Macrolide prophylaxis is associated with improved survival among Asian HIV-infected patients with low CD4 cell counts and on ART. This study suggests the increased usage and coverage of macrolide prophylaxis among people living with HIV in Asia.

Background COVID-19 emerged as a major public health outbreak in late 2019. Malaysia reported its first imported case on 25th January 2020, and adopted a policy of extensive contact tracing and hospitalising of all cases. We describe the clinical characteristics of COVID-19 cases nationwide and determine the risk factors associated with disease severity. Method Clinical records of all RT-PCR confirmed COVID-19 cases aged ≥12 years admitted to 18 designated hospitals in Malaysia between 1st February and 30th May 2020 with complete outcomes were retrieved. Epidemiological history, co-morbidities, clinical features, investigations, management and complications were captured using REDCap database. Variables were compared between mild and severe diseases. Univariate and multivariate regression were used to identify determinants for disease severity. Findings The sample comprised of 5889 cases (median age 34 years, male 71.7%). Majority were mild (92%), and 3.3% required intensive care, with 80% admitted within the first five days. Older age (≥51 years), underlying chronic kidney disease and chronic pulmonary disease, fever, cough, diarrhoea, breathlessness, tachypnoea, abnormal chest radiographs and high serum CRP (≥5 mg/dL) on admission were significant determinants for severity (p Interpretations Lower case fatality rate was possibly contributed by young cases with mild diseases and early hospitalisation. Abnormal chest radiographic findings in elderly with tachypnoea require close monitoring in the first five days to detect early deterioration.

Missed clinic visits can lead to poorer treatment outcomes in HIV-infected patients. Suboptimal antiretroviral therapy (ART) adherence has been linked to subsequent missed visits. Knowing the determinants of missed visits in Asian patients will allow for appropriate counselling and intervention strategies to ensure continuous engagement in care. A missed visit was defined as having no assessments within six months. Repeated measures logistic regression was used to analyse factors associated with missed visits. A total of 7100 patients were included from 12 countries in Asia with 2676 (37.7%) having at least one missed visit. Patients with early suboptimal self-reported adherence95% were more likely to have a missed visit compared to those with adherence ≥95% (OR = 2.55, 95% CI(1.81-3.61)). Other factors associated with having a missed visit were homosexual (OR = 1.45, 95%CI(1.27-1.66)) and other modes of HIV exposure (OR = 1.48, 95%CI(1.27-1.74)) compared to heterosexual exposure; using PI-based (OR = 1.33, 95%CI(1.15-1.53) and other ART combinations (OR = 1.79, 95%CI(1.39-2.32)) compared to NRTI+NNRTI combinations; and being hepatitis C co-infected (OR = 1.27, 95%CI(1.06-1.52)). Patients aged30 years (31-40 years OR = 0.81, 95%CI(0.73-0.89); 41-50 years OR = 0.73, 95%CI(0.64-0.83); and50 years OR = 0.77, 95%CI(0.64-0.93)); female sex (OR = 0.81, 95%CI(0.72-0.90)); and being from upper middle (OR = 0.78, 95%CI(0.70-0.80)) or high-income countries (OR = 0.42, 95%CI(0.35-0.51)), were less likely to have missed visits. Almost 40% of our patients had a missed clinic visit. Early ART adherence was an indicator of subsequent clinic visits. Intensive counselling and adherence support should be provided at ART initiation in order to optimise long-term clinic attendance and maximise treatment outcomes.

Antibiotic resistance is one of the biggest threats to global public health. Misuse of antibiotics has never been investigated on a nationwide scale among the general public in Malaysia. This study aimed to identify sociodemographic and knowledge factors associated with inappropriate use of antibiotics in the Malaysian context to inform the development of interventions to mitigate inappropriate antibiotic use. We conducted computer-assisted telephone interviews (CATI) between June 2019 and December 2019. The telephone numbers were randomly generated from the electronic residential telephone directory of all 13 states and 3 Federal Territories in Malaysia. The survey consisted of questions on demographics, knowledge about antibiotics and antibiotic resistance (53 items), and practices of antibiotic use (16 questions). A total of 864 complete responses were received. Pronounced erroneous beliefs that antibiotics are effective against infections caused by viruses and that antibiotics can speed up recovery from coughs and colds were evident. The proportions that were aware of the terms ‘drug resistance’, ‘antimicrobial resistance’, and ‘superbugs’ were low. The mean and standard deviation (SD) for the antibiotic knowledge score was 23.7 (SD ±9.25; range 0 to 50) out of a possible score of 52. Regarding antibiotic practices, a considerable proportion reported non-adherence to recommended doses. The mean and SD for the antibiotic practices score was 37.9 (SD ± 6.5; range 17 to 47) out of a possible score of 48. Participants who earned an average monthly household income of MYR1001-3000 (OR 1.61, 95% CI 1.04–2.50) were more likely to report higher antibiotic practice scores than those with

Introduction: Multiple comorbidities among HIV-positive individuals may increase the potential for polypharmacy causing drug-to-drug interactions and older individuals with comorbidities, particularly those with cognitive impairment, may have difficulty in adhering to complex medications. However, the effects of age-associated comorbidities on the treatment outcomes of combination antiretroviral therapy (cART) are not well known. In this study, we investigated the effects of age-associated comorbidities on therapeutic outcomes of cART in HIV-positive adults in Asian countries. Methods: Patients enrolled in the TREAT Asia HIV Observational Database cohort and on cART for more than six months were analysed. Comorbidities included hypertension, diabetes, dyslipidaemia and impaired renal function. Treatment outcomes of patients ≥50 years of age with comorbidities were compared with those

Dengue is one of the most important arthropod-borne viral infection in human. Numerous factors have been attributed to the severity of dengue infection, including host genome variation. Genomic structural variations such as copy number variation (CNVs), constitutes a substantial fraction of the human genetic variability, but its role in susceptibility to infectious diseases is not well understood. Previous studies have confirmed the role of host candidate gene CD209 variation in the susceptibility to dengue. Although the CNV of this gene has been reported in the Database of Genomic Variants (DGV), its characterization has yet to be studied. Therefore we aimed to characterize the CNV of the candidate gene CD209 among dengue fever and dengue hemorrhagic fever patients from Malaysia. We found that 19% of the dengue patients had copy number loss (copy number 2). Analysis of genetic association between the gene copy number and vascular leakage in dengue revealed no statistical significance ( P = 0.9043), suggesting minimal contribution of CD209 CNV in the aetiology of dengue hemorrhagic fever. Further investigation with higher number of samples, however, is needed to confirm this finding.

Treatment interruptions (TIs) of combination antiretroviral therapy (cART) are known to lead to unfavourable treatment outcomes but do still occur in resource-limited settings. We investigated the effects of TI associated with adverse events (AEs) and non-AE-related reasons, including their durations, on treatment failure after cART resumption in HIV-infected individuals in Asia.Patients initiating cART between 2006 and 2013 were included. TI was defined as stopping cART for1 day. Treatment failure was defined as confirmed virological, immunological or clinical failure. Time to treatment failure during cART was analysed using Cox regression, not including periods off treatment. Covariables with P0.10 in univariable analyses were included in multivariable analyses, where P0.05 was considered statistically significant.Of 4549 patients from 13 countries in Asia, 3176 (69.8%) were male and the median age was 34 years. A total of 111 (2.4%) had TIs due to AEs and 135 (3.0%) had TIs for other reasons. Median interruption times were 22 days for AE and 148 days for non-AE TIs. In multivariable analyses, interruptions30 days were associated with failure (31-180 days HR = 2.66, 95%CI (1.70-4.16); 181-365 days HR = 6.22, 95%CI (3.26-11.86); and365 days HR = 9.10, 95% CI (4.27-19.38), all P0.001, compared to 0-14 days). Reasons for previous TI were not statistically significant (P = 0.158).Duration of interruptions of more than 30 days was the key factor associated with large increases in subsequent risk of treatment failure. If TI is unavoidable, its duration should be minimised to reduce the risk of failure after treatment resumption.

Many HIV-infected individuals do not enter health care until late in the infection course. Despite encouraging earlier testing, this situation has continued for several years. We investigated the prevalence of late presenters and factors associated with late presentation among HIV-infected patients in an Asian regional cohort. This cohort study included HIV-infected patients with their first positive HIV test during 2003–2012 and CD4 count and clinical status data within 3 months of that test. Factors associated with late presentation into care (CD4 count

Hematological malignancies have continued to be highly prevalent among people living with HIV (PLHIV). This study assessed the occurrence of, risk factors for, and outcomes of hematological and nonhematological malignancies in PLHIV in Asia.Incidence of malignancy after cohort enrollment was evaluated. Factors associated with development of hematological and nonhematological malignancy were analyzed using competing risk regression and survival time using Kaplan-Meier.Of 7455 patients, 107 patients (1%) developed a malignancy: 34 (0.5%) hematological [0.08 per 100 person-years (/100PY)] and 73 (1%) nonhematological (0.17/100PY). Of the hematological malignancies, non-Hodgkin lymphoma was predominant (n = 26, 76%): immunoblastic (n = 6, 18%), Burkitt (n = 5, 15%), diffuse large B-cell (n = 5, 15%), and unspecified (n = 10, 30%). Others include central nervous system lymphoma (n = 7, 21%) and myelodysplastic syndrome (n = 1, 3%). Nonhematological malignancies were mostly Kaposi sarcoma (n = 12, 16%) and cervical cancer (n = 10, 14%). Risk factors for hematological malignancy included age50 vs. ≤30 years [subhazard ratio (SHR) = 6.48, 95% confidence interval (CI): 1.79 to 23.43] and being from a high-income vs. a lower-middle-income country (SHR = 3.97, 95% CI: 1.45 to 10.84). Risk was reduced with CD4 351-500 cells/µL (SHR = 0.20, 95% CI: 0.05 to 0.74) and CD4500 cells/µL (SHR = 0.14, 95% CI: 0.04 to 0.78), compared to CD4 ≤200 cells/µL. Similar risk factors were seen for nonhematological malignancy, with prior AIDS diagnosis showing a weak association. Patients diagnosed with a hematological malignancy had shorter survival time compared to patients diagnosed with a nonhematological malignancy.Nonhematological malignancies were common but non-Hodgkin lymphoma was more predominant in our cohort. PLHIV from high-income countries were more likely to be diagnosed, indicating a potential underdiagnosis of cancer in low-income settings.

Purpose Renal disease is common among people living with human immunodeficiency virus (HIV). However, there is limited information on the incidence and risk factors associated with renal dysfunction among this population in Asia. Methods We used data from the TREAT Asia HIV Observational Database. Patients were included if they started antiretroviral therapy during or after 2003, had a serum creatinine measurement at antiretroviral therapy initiation (baseline), and had at least 2 follow-up creatinine measurements taken ≥3 months apart. Patients with a baseline estimated glomerular filtration rate (eGFR) ≤60 mL/min/1.73 m2 were excluded. Chronic kidney disease was defined as 2 consecutive eGFR values ≤60 mL/min/1.73 m2 taken ≥3 months apart. Generalized estimating equations were used to identify factors associated with eGFR change. Competing risk regression adjusted for study site, age and sex, and cumulative incidence plots were used to evaluate factors associated with chronic kidney disease (CKD). Results Of 2547 patients eligible for this analysis, tenofovir was being used by 703 (27.6%) at baseline. Tenofovir use, high baseline eGFR, advanced HIV disease stage, and low nadir CD4 were associated with a decrease in eGFR during follow-up. Chronic kidney disease occurred at a rate of 3.4 per 1000 patient/years. Factors associated with CKD were tenofovir use, old age, low baseline eGFR, low nadir CD4, and protease inhibitor use. Conclusions There is an urgent need to enhance renal monitoring and management capacity among at-risk groups in Asia and improve access to less nephrotoxic antiretrovirals.

Introduction Cotrimoxazole (CTX) is recommended as prophylaxis against Pneumocystis jiroveci pneumonia, malaria and other serious bacterial infections in HIV‐infected patients. Despite its in vitro activity against Mycobacterium tuberculosis, the effects of CTX preventive therapy on tuberculosis (TB) remain unclear. Methods Adults living with HIV enrolled in a regional observational cohort in Asia who had initiated combination antiretroviral therapy (cART) were included in the analysis. Factors associated with new TB diagnoses after cohort entry and survival after cART initiation were analysed using Cox regression, stratified by site. Results A total of 7355 patients from 12 countries enrolled into the cohort between 2003 and 2016 were included in the study. There were 368 reported cases of TB after cohort entry with an incidence rate of 0.99 per 100 person‐years (/100 pys). Multivariate analyses adjusted for viral load (VL), CD4 count, body mass index (BMI) and cART duration showed that CTX reduced the hazard for new TB infection by 28% (HR 0.72, 95% CI l 0.56, 0.93). Mortality after cART initiation was 0.85/100 pys, with a median follow‐up time of 4.63 years. Predictors of survival included age, female sex, hepatitis C co‐infection, TB diagnosis, HIV VL, CD4 count and BMI. Conclusions CTX was associated with a reduction in the hazard for new TB infection but did not impact survival in our Asian cohort. The potential preventive effect of CTX against TB during periods of severe immunosuppression should be further explored.

BACKGROUND Current treatment guidelines for HIV infection recommend routine CD4 lymphocyte (CD4) count monitoring in patients with viral suppression. This may have a limited impact on influencing care as clinically meaningful CD4 decline rarely occurs during viral suppression. METHODS In a regional HIV observational cohort in the Asia-Pacific region, patients with viral suppression (2 consecutive viral loads

Elevated CD8 counts with combination antiretroviral therapy (cART) initiation may be an early warning indicator for future treatment failure. Thus, we investigated whether elevated CD8 counts were associated with virological failure (VF) in the first 4 years of cART in Asian HIV-infected patients in a multicenter regional cohort. We included patients from the TREAT Asia HIV Observational Database (TAHOD). Patients were included in the analysis if they started cART between 1996 and 2013 with at least one CD8 measurement within 6 months prior to cART initiation and at least one CD8 and viral load (VL) measurement beyond 6 months after starting cART. We defined VF as VL ≥400 copies/mL after 6 months on cART. Elevated CD8 was defined as CD8 ≥1200 cells/μL. Time to VF was modeled using Cox regression analysis, stratified by site. In total, 2475 patients from 19 sites were included in this analysis, of whom 665 (27%) experienced VF in the first 4 years of cART. The overall rate of VF was 12.95 per 100 person-years. In the multivariate model, the most recent elevated CD8 was significantly associated with a greater hazard of VF (HR = 1.35, 95% CI 1.14–1.61; P = 0.001). However, the sensitivity analysis showed that time-lagged CD8 measured at least 6 months prior to our virological endpoint was not statistically significant (P = 0.420). This study indicates that the relationship between the most recent CD8 count and VF was possibly due to the CD8 cells reacting to the increase in VL rather than causing the VL increase itself. However, CD8 levels may be a useful indicator for VF in HIV-infected patients after starting cART.

We read with interest the recent letter by van Griensven and colleagues published in the 1st April, 2014 edition of JAIDS.1 Using routinely collected, cross-sectional data from HIV-infected patients attending the Sihanouk Hospital Center of HOPE, Phnom Penh, Cambodia the authors generated a clinical prediction tool (CPT) for targeted creatinine testing during pre-antiretroviral therapy (ART) evaluation. Such a tool may prevent superfluous renal function assessment prior to initiating the nephrotoxic antiretroviral, tenofovir. This will become increasingly important in coming years given the World Health Organisation’s (WHO’s) recommendation of tenofovir in first-line ART 2, 3 and expanding global use of tenofovir.4-7 Details on the generation of the CPT can be found in van Griensven et al 1 and elsewhere.8-11 The primary outcome was kidney dysfunction (KD) at pre-ART evaluation, defined as an estimated creatinine clearance 50% (sensitivity 90.8%, specificity 52.9% with cutoff score at ≥1). A cutoff score of ≥2 for the primary CPT also performed well in the TAHOD cohort (sensitivity 85.1%, specificity 59.3%) and was the pick of the CPTs in van Griensven’s validation cohort (sensitivity 91.5%, specificity 54.7%). Nevertheless, since the aim of the CPT is to avert unnecessary creatinine testing, the primary CPT, which requires a blood test result (haemoglobin), may not be entirely logical. The alternate CPT only needs basic patient data and a medical history. With a cutoff score of ≥2, it performed reasonably well in our independent validation. Sensitivity was 86.5% and specificity was 56.0%, which translates to 54.1% of patients avoiding creatinine testing during their pre-ART evaluation and 13.5% of patients with KD being considered fit to initiate tenofovir. We believe this may be a clinically acceptable tool, however future investigation will need to confirm its cost-effectiveness. Serum creatinine testing is not particularly expensive in Asia (approximately $US3 per test at one TAHOD centre in Thailand) whilst the cost of managing a patient with chronic renal failure may be substantial. Using data from a large, multicentre cohort of HIV-infected patients in Asia, we have provided supportive evidence for a CPT that could limit unnecessary renal function testing prior to tenofovir initiation. Further validation and cost-effectiveness analysis is required and will need to consider the savings achievable with this tool as tenofovir use expands. Optimising resources is of the utmost importance to the sustained global scale-up of ART.

A total of 693 HIV/AIDS patients were recruited in this retrospective and descriptive study during April 2003 to December 2004, Hospital Kuala Lumpur, Malaysia. It was found that both genders were shown to be within the same range of age (M = 18-79 vs F = 18-73), while a median age was slightly higher in male (36 years) than female (31 years). The majority of both genders were significantly shown in the age group of 25 to 34 years, but a higher rate was evident in females (42) (p = 0.001). It was even observed that male patients were mainly Chinese (44.7) and single (57.3) (p = 0.001), while the females were Chinese (40.6) and married (83.3) (p = 0.000). However, the highest numbers of both genders were manifested to be heterosexuals (M = 47.6 vs F = 86.2), followed by intravenous drug users (M = 39.3 vs F = 6.5) (p = 0.000). The range of CD4 cell count was 0 to 1799 with a median of 230 cells/mm3. The level of CD4 cell count of < 200 cells/mm3 was significantly found in males (48.5) and between 200 to 499 and �500 cells/mm3 were 36.2 and 26.8 in females, respectively (p = 0.001). Overall, the Toxoplasma seroprevalence was 43.85 where seropositive of anti-Toxoplasma antibody relatively higher in males (50) than in females (37.7) (p = 0.015). Toxoplasma seropositivity was thoroughly evident among Malays (168; 51.1), Intravenous Drug Users (IDUs) and patients with toxoplasmic encephalitis (TE) (p = 0.001). Furthermore, anti-retroviral therapy including HAART was more significantly found in patients with 9 seropositive Toxoplasma when compared to 2 seronegative and unknown serostatus patients (p = 0.025). Seventeen AIDS-related toxoplasmic encephalitis patients were diagnosed at the time of this study, depicting hemiparesis as the most common neurological manifestation in 11 (64.7) patients, followed by headache and seizure in 6 (35.3) and 3 (17.7) patients, respectively. Interestingly, CT scan finding showed mass like structure with multiple (58.8), ring enhancing lesions (100), in parietal region (58.8) and edema (29.4) in these patients. Overall, the treatment outcome showed that 13 (76.5) patients had completed treatment with maintenance, whereas, 3 (17.6) patients were lost to follow up and 1 (6) patient was transferred to another hospital. No relapse or death case was reported during the time of this study.

The FCGR3 locus encoding the low affinity activating receptor FcγRIII, plays a vital role in immunity triggered by cellular effector and regulatory functions. Copy number of the genes FCGR3A and FCGR3B has previously been reported to affect susceptibility to several autoimmune diseases and chronic inflammatory conditions. However, such genetic association studies often yield inconsistent results; hence require assays that are robust with low error rate. We investigated the accuracy and efficiency in estimating FCGR3 CNV by comparing Sequenom MassARRAY and paralogue ratio test-restriction enzyme digest variant ratio (PRT-REDVR). In addition, since many genetic association studies of FCGR3B CNV were carried out using real-time quantitative PCR, we have also included the evaluation of that method’s performance in estimating the multi-allelic CNV of FCGR3B. The qPCR assay exhibited a considerably broader distribution of signal intensity, potentially introducing error in estimation of copy number and higher false positive rates. Both Sequenom and PRT-REDVR showed lesser systematic bias, but Sequenom skewed towards copy number normal (CN = 2). The discrepancy between Sequenom and PRT-REDVR might be attributed either to batch effects noise in individual measurements. Our study suggests that PRT-REDVR is more robust and accurate in genotyping the CNV of FCGR3, but highlights the needs of multiple independent assays for extensive validation when performing a genetic association study with multi-allelic CNVs.

Introduction Although substitutions of antiretroviral regimen are generally safe, most data on substitutions are based on results from clinical trials. The objective of this study was to evaluate the treatment outcomes of substituting antiretroviral regimen in virologically suppressed HIV‐infected patients in non‐clinical trial settings in Asian countries. Methods The study population consisted of HIV‐infected patients enrolled in the TREAT Asia HIV Observational Database (TAHOD). Individuals were included in this analysis if they started combination antiretroviral treatment (cART) after 2002, were being treated at a centre that documented a median rate of viral load monitoring ≥0.8 tests/patient/year among TAHOD enrolees, and experienced a minor or major treatment substitution while on virally suppressive cART. The primary endpoint to evaluate outcomes was clinical or virological failure (VF), followed by an ART class change. Clinical failure was defined as death or an AIDS diagnosis. VF was defined as confirmed viral load measurements ≥400 copies/mL followed by an ART class change within six months. Minor regimen substitutions were defined as within‐class changes and major regimen substitutions were defined as changes to a drug class. The patterns of substitutions and rate of clinical or VF after substitutions were analyzed. Results Of 3994 adults who started ART after 2002, 3119 (78.1%) had at least one period of virological suppression. Among these, 1170 (37.5%) underwent a minor regimen substitution, and 296 (9.5%) underwent a major regimen substitution during suppression. The rates of clinical or VF were 1.48/100 person years (95% CI 1.14 to 1.91) in the minor substitution group, 2.85/100 person years (95% CI 1.88 to 4.33) in the major substitution group and 2.53/100 person years (95% CI 2.20 to 2.92) among patients that did not undergo a treatment substitution. Conclusions The rate of clinical or VF was low in both major and minor substitution groups, showing that regimen substitution is generally effective in non‐clinical trial settings in Asian countries.

Objective.To determine the relationship between methicillin-resistant Staphylococcus aureus (MRSA) colonization density, colonization site, and probability of infection in a frequently screened cohort of intensive care unit (ICU) patients.Methods.Patients had swab samples tested for MRSA at admission to the ICU, discharge from the ICU, and twice weekly during their ICU stay, and they were followed up for development of MRSA infection. Swab test results were analyzed to determine the proportion of patients colonized and the proportion colonized at each screening site. Hazard of MRSA infection (rate of infection per day at risk) was calculated using a Cox proportional hazards analysis, and risk factors for MRSA infection, including presence of MRSA, degree of colonization, and pattern of colonization were determined.Results.Among the 4,194 patient episodes, 238 (5.7%) had screening results that were positive for MRSA, and there were 34 cases of MRSA infection. The hazard ratio (HR) for developing an infection increased as more sites were colonized (HR, 3.4 for being colonized at more than 1 site compared with colonization at 1 site [95% confidence interval, 1.2-9.9]). Colonization site was predictive of developing infection (HR for nose or throat colonization compared with no colonization, 168 [95% confidence interval, 69-407]).Conclusion.This study demonstrated that the hazard of developing an infection was higher when more sites were colonized and that certain sites were more predictive of infection than others. These results may be useful for predicting infection in ICU patients and may influence treatment.

Tuberculosis (TB) continues to be a major public health problem and challenge despite control programmes being implemented worldwide. The global resurgence of TB has been accompanied by an increased frequency of multi-drug-resistant Mycobacterium tuberculosis (MDR-TB). In Malaysia TB is among the top five communicable diseases reported with 15643 14820 and 14389 cases reported in 2000 2001 and 2002 respectively and a mean mortality rate of 6.2/100000 population. TB is a disease of major impact in Malaysia and few data are available on gender differences of pulmonary tuberculosis (PTB) in non-HIV-infected patients. The aim of this study was to improve understanding and management of this resurgent but curable disease. (excerpt)

BACKGROUND: Currently, there is a lack of vital information in the genetic makeup of Cryptosporidium especially in developing countries. The present study aimed at determining the genotypes and subgenotypes of Cryptosporidium in hospitalized Malaysian human immunodeficiency virus (HIV) positive patients. METHODOLOGY/PRINCIPAL FINDINGS: In this study, 346 faecal samples collected from Malaysian HIV positive patients were genetically analysed via PCR targeting the 60 kDa glycoprotein (gp60) gene. Eighteen (5.2% of 346) isolates were determined as Cryptosporidium positive with 72.2% (of 18) identified as Cryptosporidium parvum whilst 27.7% as Cryptosporidium hominis. Further gp60 analysis revealed C. parvum belonging to subgenotypes IIaA13G1R1 (2 isolates), IIaA13G2R1 (2 isolates), IIaA14G2R1 (3 isolates), IIaA15G2R1 (5 isolates) and IIdA15G1R1 (1 isolate). C. hominis was represented by subgenotypes IaA14R1 (2 isolates), IaA18R1 (1 isolate) and IbA10G2R2 (2 isolates). CONCLUSIONS/SIGNIFICANCE: These findings highlighted the presence of high diversity of Cryptosporidium subgenotypes among Malaysian HIV infected individuals. The predominance of the C. parvum subgenotypes signified the possibility of zoonotic as well as anthroponotic transmissions of cryptosporidiosis in HIV infected individuals.