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Background: Treatment understanding and experiences are vital to determine HIV patients' adherence and retention to care. Methods: Indepth patient interviews were audio-recorded, with a prior verbal and written consent and subjected to a thematic content analysis framework for data analysis. Results: Though majority of participants believed in Antiretroviral Therapy (ART) as the most effective way of treatment, they were greatly worried about its toxicities. Disease understanding and peer influence were regarded as the main reasons for treatment initiation; whereas, perceived side effects and lack of support system were among the main reasons associated with treatment delay. Almost all the patients experienced toxicities due to ARTs and viewed it negatively impacting their quality of life. Conclusion: It is vital for People Living with HIV/AIDS (PLWHA) to be retained in care; hence, the provision of optimal care with greater support to overcome treatment challenges must be focused in any HIV program. [ABSTRACT FROM AUTHOR]

Background: Understanding patients’ perspective towards HIV screening in Malaysia is pivotal to explore challenges faced by these individuals. This would be beneficial for developing local plans to improve the health-seeking behaviours among population at risk of HIV/AIDS. Methods: A qualitative research methodology was adopted to explore HIV/AIDS patients’ views about disease screening. A semi-structured interview guide was used for in-depth patient interviews. All interviews were audio-recorded and were subjected to a standard content analysis framework for data analysis. Results: Most patients were positive about screening and the value of knowing about their status early. However, fear of social stigma, discrimination, lack of support system and lack of public understanding were identified as major concerns affecting their willingness to be screened. They were concerned about mandatory screening being implemented without improvement in support system and public education. Conclusions: Reluctance to seek HIV screening is an important factor contributing to transmission in developing countries. In the Malaysian context, efforts should be made to strengthen screening strategies especially in the most-at-risk populations to monitor the epidemic and target prevention strategies. Practice implications: In a multicultural context, HIV preventive strategies must include disease awareness, including measure to tackle barriers towards screening. [ABSTRACT FROM AUTHOR]

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ABSTRACT Extraction of high molecular weight chromosomal DNA from yeast cells is a procedure that is performed frequently for experiments involving polymerase chain reaction (PCR), Southern blotting and other DNA analysis techniques. We have investigated several parameters affecting DNA yield and quality, using a simple chemical-based purification procedure that was modelled on alkaline lysis methods developed for bacterial cells. The three major steps of the procedure, cell lysis, protein removal and DNA precipitation, were optimized by testing the impacts of several chemicals, including sodium dodecyl sulphate (SDS), sodium hydroxide, Tris buffer, sodium acetate and potassium acetate. Other parameters, such as the effect of elevated temperatures on cell lysis, were also investigated. A rapid, optimized protocol was derived for the purification of DNA from small cell cultures that can be readily digested with restriction enzymes and used as a template for PCR. Average yield was calculated to be approximately 1.7 µg DNA/108 cells, which is similar to the theoretical maximum amount obtainable from haploid yeast cells. Copyright © 2011 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Background: Accurate interpretation of HIV drug resistance (HIVDR) testing is challenging, yet important for patient care. We compared genotyping interpretation, based on the Stanford University HIV Drug Resistance Database (Stanford HIVdb), and virtual phenotyping, based on the Janssen Diagnostics BVBA's vircoTYPE™HIV-1, and investigated their level of agreement in antiretroviral (ARV) naive patients in Asia, where non-B subtypes predominate. Methods: Sequences from 1301 ARV-naive patients enrolled in the TREAT Asia Studies to Evaluate Resistance--Monitoring Study (TASER-M) were analysed by both interpreting systems. Interpretations from both Stanford HIVdb and vircoTYPE™HIV-1 were initially grouped into 2 levels: susceptible and non-susceptible. Discrepancy was defined as a discordant result between the susceptible and non-susceptible interpretations from the two systems for the same ARV. Further analysis was performed when interpretations from both systems were categorised into 3 levels: susceptible, intermediate and resistant; whereby discrepancies could be categorised as major discrepancies and minor discrepancies. Major discrepancy was defined as having a susceptible result from one system and resistant from the other. Minor discrepancy corresponded to having an intermediate interpretation in one system, with a susceptible or resistant result in the other. The level of agreement was analysed using the prevalence adjusted bias adjusted kappa (PABAK). Results: Overall, the agreement was high, with each ARV being in "almost perfect agreement", using Landis and Koch's categorisation. Highest discordance was observed for efavirenz (75/1301, 5.8%), all arising from susceptible Stanford HIVdb versus non-susceptible vircoTYPE™ HIV-1 predictions. Protease Inhibitors had highest level of concordance with PABAKs all above 0.99, followed by Nucleoside Reverse Transcriptase Inhibitors with PABAKs above 0.97 and non-NRTIs with the lowest PABAK of 0.88. The 68/75 patients with discordant efavirenz results harboured the V179D/E mutations compared to 7/1226 with no efavirenz discrepancy (p-value <0.001). In the 3-level comparison, all but one of the discrepancies was minor. Conclusions: The two systems agreed well with lowest concordance observed for efavirenz. When interpreting HIVDR, especially in non-B subtypes, clinical correlation is crucial, in particular when efavirenz resistance is interpreted based on V179D/E. [ABSTRACT FROM AUTHOR]

Background: Pneumocystis jiroveci pneumonia (PCP) prophylaxis is recommended for patients with CD4 counts of less than 200 cells/mm3. This study examines the proportion of patients in the TREAT Asia HIV Observational Database (TAHOD) receiving PCP prophylaxis, and its effect on PCP and mortality. Methods: TAHOD patients with prospective follow up had data extracted for prophylaxis using co-trimoxazole, dapsone or pentamidine. The proportion of patients on prophylaxis was calculated for each calendar year since 2003 among patients with CD4 counts of less than 200 cells/mm3. The effect of prophylaxis on PCP and survival were assessed using random-effect Poisson regression models. Results: There were a total of 4050 patients on prospective follow up, and 90% of them were receiving combination antiretroviral therapy. Of those with CD4 counts of less than 200 cells/mm3, 58% to 72% in any given year received PCP prophylaxis, predominantly co-trimoxazole. During follow up, 62 patients developed PCP (0.5 per 100 person-years) and 169 died from all causes (1.36/100 person-years). After stratifying by site and adjusting for age, CD4 count, CDC stage and antiretroviral treatment, those without prophylaxis had no higher risk of PCP, but had a significantly higher risk of death (incident rate ratio 10.8, p < 0.001). PCP prophylaxis had greatest absolute benefit in patients with CD4 counts of less than 50 cells/mm3, lowering mortality rates from 33.5 to 6.3 per 100 person-years. Conclusions: Approximately two-thirds of TAHOD patients with CD4 counts of less than 200 cells/mm3 received PCP prophylaxis. Patients without prophylaxis had significantly higher mortality, even in the era of combination ART. Although PCP may be under-diagnosed, these data suggest that prophylaxis is associated with important survival benefits. [ABSTRACT FROM AUTHOR]

Of 682 antiretroviral-na_ve patients initiating antiretroviral therapy in a prospective, multicenter HIV-1 drug resistance monitoring study involving eight sites in Hong Kong, Malaysia, and Thailand, the prevalence of patients with ≥1 drug resistance mutation(s) was 13.8%. Primary HIV drug resistance is emerging after rapid scaling-up of antiretroviral therapy in Asia.(See editorial commentary by Jordan on pages 1058–1060.)Of 682 antiretroviral-naïve patients initiating antiretroviral therapy in a prospective, multicenter human immunodeficiency virus type 1 (HIV-1) drug resistance monitoring study involving 8 sites in Hong Kong, Malaysia, and Thailand, the prevalence of patients with ≥1 drug resistance mutation was 13.8%. Primary HIV drug resistance is emerging after rapid scaling-up of antiretroviral therapy use in Asia. [ABSTRACT FROM AUTHOR]

Background: The aim of this study was to examine the relationship between trends in CD4 counts (slope) and HIV viral load (VL) after initiation of combination antiretroviral treatment (cART) in Asian patients in The TREAT Asia HIV Observational Database (TAHOD). Methods: Treatment-naive HIV-infected patients who started cART with three or more and had three or more CD4 count and HIV VL tests were included. CD4 count slopes were expressed as changes of cells per microliter per year. Predictors of CD4 count slopes from 6 months after initiation were assessed by random-effects linear regression models. Results: A total of 1676 patients (74% male) were included. The median time on cART was 4.2 years (IQR 2.5-5.8 years). In the final model, CD4 count slope was associated with age, concurrent HIV VL and CD4 count, disease stage, hepatitis B or C co-infection, and time since cART initiation. CD4 count continues to increase with HIV VL up to 20 000 copies/mL during 6-12 months after cART initiation. However, the HIV VL has to be controlled below 5 000, 4 000 and 500 copies/mL for the CD4 count slope to remain above 20 cells/microliter per year during 12-18, 18-24, and beyond 24 months after cART initiation. Conclusions: After cART initiation, CD4 counts continued to increase even when the concurrent HIV VL was detectable. However, HIV VL needed to be controlled at a lower level to maintain a positive CD4 count slope when cART continues. [ABSTRACT FROM AUTHOR]

Background: This retrospective survey describes types of cancers diagnosed in HIV-infected subjects in Asia, and assesses risk factors for cancer in HIV-infected subjects using contemporaneous HIV-infected controls without cancer. Methods: TREAT Asia HIV Observational Database (TAHOD) sites retrospectively reviewed clinic medical records to determine cancer diagnoses since 2000. For each diagnosis, the following data were recorded: date, type, stage, method of diagnosis, demographic data, medical history, and HIV-related information. For risk factor analyses, two HIV-infected control subjects without cancer diagnoses were also selected. Cancers were grouped as AIDS-defining cancers (ADCs), and non-ADCs. Non-ADCs were further categorized as being infection related (NADC-IR) and unrelated (NADC-IUR). Results: A total of 617 patients were included in this study: 215 cancer cases and 402 controls from 13 sites. The majority of cancer cases were male (71%). The mean age (SD) for cases was 39 (10.6), 46 (11.5) and 44 (13.7) for ADCs, NADC-IURs and NADCs-IR, respectively. The majority (66%) of cancers were ADCs (16% Kaposi sarcoma, 40% non-Hodgkin's lymphoma, and 9% cervical cancer). The most common NADCs were lung (6%), breast (5%) and hepatocellular carcinoma and Hodgkin's lymphoma (2% each). There were also three (1.4%) cases of leiomyosarcoma reported in this study. In multivariate analyses, individuals with CD4 counts above 200 cells/mm3 were approximately 80% less likely to be diagnosed with an ADC (p < 0.001). Older age (OR: 1.39, p = 0.001) and currently not receiving antiretroviral treatment (OR: 0.29, p = 0.006) were independent predictors of NADCs overall, and similarly for NADCs-IUR. Lower CD4 cell count and higher CDC stage (p = 0.041) were the only independent predictors of NADCs-IR. Conclusions: The spectrum of cancer diagnoses in the Asia region currently does not appear dissimilar to that observed in non-Asian HIV populations. One interesting finding was the cases of leiomyosarcoma, a smoothmuscle tumour, usually seen in children and young adults with AIDS, yet overall quite rare. Further detailed studies are required to better describe the range of cancers in this region, and to help guide the development of screening programmes. [ABSTRACT FROM AUTHOR]

Background: To assess the risk and the prognostic significance of tuberculosis (TB) diagnosis in patients from The TREAT Asia HIV Observational Database, a multi-centre prospective cohort of HIV-infected patients receiving HIV care in the Asia-Pacific region. Methods: The risk of TB diagnosis after recruitment was assessed in patients with prospective follow-up. TB diagnosis was fitted as a time-dependent variable in assessing overall survival. Results: At baseline, 22% of patients were diagnosed with TB. TB incidence was 1.98 per 100 person-years during follow up, with predictors including younger age, lower recent CD4 count, duration of antiretroviral treatment, and living in high TB burden countries. Among 3279 patients during 6968 person-years, 142 died (2.04 per 100 person-years). Compared to patients with CDC category A or B illness only, mortality was marginally higher in patients with single Non-TB AIDS defining illness (ADI), or TB only (adjusted HR 1.35, p = 0.173) and highest in patients with multiple non-TB AIDS or both TB and other ADI (adjusted HR 2.21, p < 0.001). Conclusion: The risk of TB diagnosis was associated with increasing immunodeficiency and partly reduced by antiretroviral treatment. The prognosis of developing TB appeared to be similar to that following a diagnosis of other non-TB ADI. [ABSTRACT FROM AUTHOR]

The author comments on the influenza A/H1N1 Pandemic in 2009, which is considered to be the next major influenza outbreak worldwide. He says the secondary attack rate of the new influenza A/H1N1 virus is higher, which is estimated at 22% to 33%, compared with that of seasonal influenza. Clinical manifestations of the virus are mentioned, including fever, cough and diarrhoea. Also outlined are the goals of the measures taken by the Malaysian Ministry of Health to mitigate the outbreak.

Introduction: The latest revised version of the World Health Organization's dengue classification was released in 2009. A handful of studies have taken initiatives to evaluate the old and revised guidelines to determine early signs and symptoms of severe dengue. This retrospective study aimed to compare the classification of dengue using both the 1997 and 2009 guidelines in a selected cohort of dengue patients from Peninsular Malaysia between 2008 and 2012. Methodology: Adult dengue patients were recruited from tertiary hospitals in two different states, Selangor and Kelantan, in Peninsular Malaysia. Their clinical manifestations were assessed. Results: A total of 281 confirmed dengue patients were enrolled; the mean duration of illness at admission was five days. Of these, 88.6%, 10.7%, and 0.7% were classified according to the 1997 guidelines as having dengue fever (DF), dengue hemorrhagic fever (DHF), and dengue shock syndrome (DSS), respectively. When the WHO 2009 guidelines were applied, 17.1%, 78.3%, and 4.6% were classified as dengue without warning signs, dengue with warning signs, and severe dengue, respectively. Conclusions: Our data suggests that the revised WHO 2009 guidelines stratify a much larger proportion of patients into a category that requires a higher level of medical and nursing care. [ABSTRACT FROM AUTHOR]

Introduction: Letters of recommendation (LOR) are an integral component of physical therapy residency applications. Identifying the influence of applicant and writer gender in LOR will help identify whether potential implicit gender bias exists in physical therapy residency application processes., Review of Literature: Several medical and surgical residency education programs have reported positive, neutral, or negative LOR female gender bias among applicants and writers. Little research exists on gender differences in LOR to physical therapy education programs or physical therapy residency programs., Subjects: Seven hundred sixty-eight LOR were analyzed from 256 applications to 3 physical therapy residency programs (neurologic, orthopaedic, sports) at one institution from 2014 to 2020., Methods: Thematic categories were developed to identify themes in a sample of LOR. Associations between writer and applicant gender were analyzed using summary statistics, word counts, thematic and psycholinguistic extraction, and rule-based and deep learning Natural Language Processing ., Results: No significant difference in LOR word counts were found based on writer or applicant gender. Increased word counts were seen in sports residency LOR compared with the orthopaedic residency. Thematic analysis showed LOR gender differences with male applicants receiving more positive generalized recommendations and female applicants receiving more comments regarding interpersonal relationship skills. No thematic or psycholinguistic gender differences were seen by LOR writer. Male applicants were 1.9 times more likely to select all male LOR writers, whereas female applicants were 2.1 times more likely to choose all female LOR writers., Discussion and Conclusion: Gender differences in LORs for physical therapy residencies were found using a comprehensive Natural Language Processing approach that identified both a positive recommendation male applicant gender bias and a positive interpersonal relationship skill female applicant gender bias. Applicants were not harmed nor helped by selecting LOR writers of the opposite gender. Admissions committees and LOR writers should be mindful of potential implicit gender biases in LOR submitted to physical therapy residency programs., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2024 Academy of Physical Therapy Education, APTA.)

Gender stereotyping is the practice of assigning or ascribing specific characteristics, differences, or identities to a person solely based on their gender. Biased conceptions of gender can create barriers to equality and need to be proactively identified and addressed. In biomedical education, letters of recommendation (LOR) are considered an important source for evaluating candidates' past performance. Because LOR is subjective and has no standard formatting requirements for the writer, potential language bias can be introduced. Natural language processing (NLP) offers a promising solution to detect language bias in LOR through automatic extraction of sensitive language and identification of letters with strong biases. In our study, we developed, evaluated, and deployed four NLP different methods (sublanguage analysis, dictionary-based approach, rule-based approach, and deep learning approach) for the extraction of psycholinguistics and thematic characteristics in LORs from three different physical therapy residency programs (Neurologic, Orthopaedic, and Sport) at Mayo Clinic. The evaluation statistics suggest that both MedTaggerIE model and Bidirectional Encoder Representations from Transformers model achieved moderate-high performance across eight different thematic categories. Through the pilot demonstration study, we learned that male writers were more likely to use the words 'intelligence', 'exceptional', and 'pursue' and male applicants were more likely to have the words 'strength', 'interpersonal skills', 'conversations', and 'pursue' in their letters of recommendation. Thematic analysis suggested that male and female writers have significant differences in expressing doubt, motivation, and recommendation. Findings derived from the study needed to be carefully interpreted based on the context of the study setting, residency programs, and data. A follow-up demonstration study is needed to further evaluate and interpret the findings., (©2023 AMIA - All rights reserved.)

A tandem acetylene-activated S N Ar-anionic cyclization strategy is presented for the synthesis of chalcogen-containing hetero[5]helicenes. Oxa-, thia-, and selena[5]helicenes are accessed from common ortho -fluoro-ethynylarene precursors, allowing the heteroatoms to be installed at the 1-position or 1- and 12-positions of the hetero[5]helicene inner core surface.

Endothelial cells (EC), especially the microvascular EC (MVEC), have critical functions in health and disease. For example, healthy MVEC provide a barrier between the fluid and protein found within the blood, and the surrounding tissue. Following tissue injury or infection, the microvascular barrier is often disrupted due to activation and dysfunction of the MVEC. Multiple mechanisms promote MVEC activation and dysfunction, including stimulation by cytokines, mechanical interaction with activated leukocytes, and exposure to harmful leukocyte-derived molecules, which collectively result in a loss of MVEC barrier function. However, MVEC activation is also critical to facilitate recruitment of inflammatory cells, such as neutrophils (PMNs) and monocytes, into the injured or infected tissue. Metalloproteinases, including the matrix metalloproteinases (MMPs) and the closely related, a disintegrin and metalloproteinases (ADAMs), have been implicated in regulating both MVEC barrier function, through cleavage of adherens and tight junctions proteins between adjacent MVEC and through degradation of the extracellular matrix, as well as PMN-MVEC interaction, through shedding of cell surface PMN receptors. Moreover, the tissue inhibitors of metalloproteinases (TIMPs), which collectively inhibit most MMPs and ADAMs, are critical regulators of MVEC activation and dysfunction through their ability to inhibit metalloproteinases and thereby promote MVEC stability. However, TIMPs have been also found to modulate MVEC function through metalloproteinase-independent mechanisms, such as regulation of vascular endothelial growth factor signaling. This chapter is focused on examining the role of the metalloproteinases and TIMPs in regulation of MVEC function in both health and disease., (© 2017 Elsevier Inc. All rights reserved.)

Suboptimal viral suppression and CD4 response to antiretroviral treatment (HAART) is known to cause poor outcomes with the increase cost of treatment. We aimed to assess factors associated with such control among HIV/AIDS patients in Malaysia. Four hundred and six HIV/AIDS patients, using Antiretroviral Therapy (ART) for at least the past three months, treated as outpatients at medication therapy adherence clinics (MTAC) were recruited. CD4 cell counts, viral load readings along with co-variants such as socio-demographic factors, adverse drug reactions, comorbidities, and medication record were obtained. Statistical Package for Social Sciences (SPSS(®)) version 18 and STATA IC(®) version 12 were used for data analysis. CD4 counts were found highest among those within the age category 41-50 years (390.43 ± 272.28), female (402.64 ± 276.14), other ethnicities (400.20 ± 278.04), and participants with no formal education (414.87 ± 290.90). Patients experiencing adverse effects had a 2.28 (95%CI:1.25-4.18) fold greater risk of poor CD4 control, while patients with comorbidities had 2.46 (95%CI:1.02-5.91) fold greater risk of mild viral suppression. Adverse drug reactions, co-morbidities were found to be significantly associated with poor immunological and virological outcomes in HIV/AIDS patients. However, a comprehensive evaluation is needed to better understand other confounders., (© 2015 Wiley Periodicals, Inc.)

Background: Understanding patients' knowledge and belief towards disease could play a vital role from an outcome perspective of disease management and HIV/AIDS patients are not exception to that., Methods: Qualitative methodology was used to explore Malaysian HIV/AIDS patients' perspectives on disease and status disclosure. A semi structured interview guide was used to interview the patients and a saturation point was reached after the 13th interview. All interviews were audio-recorded and subjected to a standard content analysis framework., Results: Understandings and beliefs towards HIV/AIDS and Perspective on disease disclosures were two main themes derived from patients' data. Beliefs towards causes and cure emerged as sub-themes under disease understandings while reasons for disclosure and non-disclosure were resulted as main sub-themes under disease disclosure. Majority of patients apprehended HIV/AIDS and its causes to acceptable extent, there were elements of spirituality and lack of education involved with such understandings. Though beliefs existed that knowing status is better than being ignorant, fear of stigma and discrimination, social consequences and family emotions were found important elements linked to disease non-disclosure., Conclusions: The outcomes provided basic information about patients' perceptions towards disease and status disclosure among HIV/AIDS patients which can help in the designing and improvising existing strategies to enhance disease awareness and acceptance and will also serve as baseline data for future research further focusing on this subject., (© 2014 John Wiley & Sons Ltd.)

Introduction: First-line antiretroviral therapy (ART) failure often results from the development of resistance-associated mutations (RAMs). Three patterns, including thymidine analogue mutations (TAMs), 69 Insertion (69Ins) and the Q151M complex, are associated with resistance to multiple-nucleoside reverse transcriptase inhibitors (NRTIs) and may compromise treatment options for second-line ART., Methods: We investigated patterns and factors associated with multi-NRTI RAMs at first-line failure in patients from The TREAT Asia Studies to Evaluate Resistance - Monitoring study (TASER-M), and evaluated their impact on virological responses at 12 months after switching to second-line ART. RAMs were compared with the IAS-USA 2013 mutations list. We defined multi-NRTI RAMs as the presence of either Q151M; 69Ins; ≥ 2 TAMs; or M184V+≥ 1 TAM. Virological suppression was defined as viral load (VL) <400 copies/ml at 12 months from switch to second-line. Logistic regression was used to analyze (1) factors associated with multi-NRTI RAMs at first-line failure and (2) factors associated with virological suppression after 12 months on second-line., Results: A total of 105 patients from 10 sites in Thailand, Hong Kong, Indonesia, Malaysia and Philippines were included. There were 97/105 (92%) patients harbouring ≥ 1 RAMs at first-line failure, 39/105 with multi-NRTI RAMs: six with Q151M; 24 with ≥ 2 TAMs; and 32 with M184V+≥ 1 TAM. Factors associated with multi-NRTI RAMs were CD4 ≤ 200 cells/µL at genotyping (OR=4.43, 95% CI [1.59-12.37], p=0.004) and ART duration >2 years (OR=6.25, 95% CI [2.39-16.36], p<0.001). Among 87/105 patients with available VL at 12 months after switch to second-line ART, virological suppression was achieved in 85%. The median genotypic susceptibility score (GSS) for the second-line regimen was 2.00. Patients with ART adherence ≥ 95% were more likely to be virologically suppressed (OR=9.33, 95% CI (2.43-35.81), p=0.001). Measures of patient resistance to second-line ART, including the GSS, were not significantly associated with virological outcome., Conclusions: Multi-NRTI RAMs at first-line failure were associated with low CD4 level and longer duration of ART. With many patients switching to highly susceptible regimens, good adherence was still crucial in achieving virological response. This emphasizes the importance of continued adherence counselling well into second-line therapy.

Regional epidemiological data and resistance profiles are essential for selecting appropriate antibiotic therapy for intra-abdominal infections (IAIs). However, such information may not be readily available in many areas of Asia and current international guidelines on antibiotic therapy for IAIs are for Western countries, with the most recent guidance for the Asian region dating from 2007. Therefore, the Asian Consensus Taskforce on Complicated Intra-Abdominal Infections (ACT-cIAI) was convened to develop updated recommendations for antibiotic management of complicated IAIs (cIAIs) in Asia. This review article is based on a thorough literature review of Asian and international publications related to clinical management, epidemiology, microbiology, and bacterial resistance patterns in cIAIs, combined with the expert consensus of the Taskforce members. The microbiological profiles of IAIs in the Asian region are outlined and compared with Western data, and the latest available data on antimicrobial resistance in key pathogens causing IAIs in Asia is presented. From this information, antimicrobial therapies suitable for treating cIAIs in patients in Asian settings are proposed in the hope that guidance relevant to Asian practices will prove beneficial to local physicians managing IAIs.

Objective: To describe the CD4 cell count at the start of combination antiretroviral therapy (cART) in low-income (LIC), lower middle-income (LMIC), upper middle-income (UMIC), and high-income (HIC) countries., Methods: Patients aged 16 years or older starting cART in a clinic participating in a multicohort collaboration spanning 6 continents (International epidemiological Databases to Evaluate AIDS and ART Cohort Collaboration) were eligible. Multilevel linear regression models were adjusted for age, gender, and calendar year; missing CD4 counts were imputed., Results: In total, 379,865 patients from 9 LIC, 4 LMIC, 4 UMIC, and 6 HIC were included. In LIC, the median CD4 cell count at cART initiation increased by 83% from 80 to 145 cells/μL between 2002 and 2009. Corresponding increases in LMIC, UMIC, and HIC were from 87 to 155 cells/μL (76% increase), 88 to 135 cells/μL (53%), and 209 to 274 cells/μL (31%). In 2009, compared with LIC, median counts were 13 cells/μL [95% confidence interval (CI): -56 to +30] lower in LMIC, 22 cells/μL (-62 to +18) lower in UMIC, and 112 cells/μL (+75 to +149) higher in HIC. They were 23 cells/μL (95% CI: +18 to +28 cells/μL) higher in women than men. Median counts were 88 cells/μL (95% CI: +35 to +141 cells/μL) higher in countries with an estimated national cART coverage >80%, compared with countries with <40% coverage., Conclusions: Median CD4 cell counts at the start of cART increased 2000-2009 but remained below 200 cells/μL in LIC and MIC and below 300 cells/μL in HIC. Earlier start of cART will require substantial efforts and resources globally.

The prevalence of and risk factors for lipodystrophy (LD) among patients receiving combined antiretroviral treatment (cART) in the Asia-Pacific region are largely unknown. LD diagnosis was based on the adverse event definition from the US NIH Division of AIDS (2004 version), and only cases with a severity grade of ≥ 3 were included. TAHOD patients who had recently commenced cART with ≥ 3 drugs after 1996 from sites which had ever reported LD were included in the analysis. Covariates for the forward multivariate logistic regression model included demographic variables, CDC disease classification, baseline CD4 and viral load, hepatitis B/C virus co-infection, and regimen and duration of cART. LD was diagnosed in 217 (10.5%) of 2072 patients. The median duration of cART was 3.8 (interquartile range, 2.2-5.3) years [stavudine, 2.0 (1.0-3.5) years; zidovudine, 1.8 (0.6-3.9) years; and protease inhibitors (PI), 2.6 (1.3-4.5) years]. In the multivariate model, factors independently associated with LD included use of stavudine (≤ 2 years vs. no experience: OR 25.46, p<0.001, > 2 years vs. no experience: OR 14.92, p<0.001), use of PI (> 2.6 years vs. no experience: OR 0.26, p<0.001), and total duration of cART (> vs. ≤ 3.8 years: OR 4.84, p<0.001). The use of stavudine was strongly associated with LD in our cohort. Stavudine-sparing cART strategies are warranted to prevent the occurrence of LD in the Asia-Pacific region.

Background: The aim of this study was to examine the relationship between trends in CD4 counts (slope) and HIV viral load (VL) after initiation of combination antiretroviral treatment (cART) in Asian patients in The TREAT Asia HIV Observational Database (TAHOD)., Methods: Treatment-naive HIV-infected patients who started cART with three or more and had three or more CD4 count and HIV VL tests were included. CD4 count slopes were expressed as changes of cells per microliter per year. Predictors of CD4 count slopes from 6 months after initiation were assessed by random-effects linear regression models., Results: A total of 1676 patients (74% male) were included. The median time on cART was 4.2 years (IQR 2.5-5.8 years). In the final model, CD4 count slope was associated with age, concurrent HIV VL and CD4 count, disease stage, hepatitis B or C co-infection, and time since cART initiation. CD4 count continues to increase with HIV VL up to 20,000 copies/mL during 6-12 months after cART initiation. However, the HIV VL has to be controlled below 5,000, 4,000 and 500 copies/mL for the CD4 count slope to remain above 20 cells/microliter per year during 12-18, 18-24, and beyond 24 months after cART initiation., Conclusions: After cART initiation, CD4 counts continued to increase even when the concurrent HIV VL was detectable. However, HIV VL needed to be controlled at a lower level to maintain a positive CD4 count slope when cART continues. The effect on long-term outcomes through the possible development of HIV drug resistance remains uncertain.