Publications by authors named "Vonthanak Saphonn"

84 Publications

Potential for community based surveillance of febrile diseases: Feasibility of self-administered rapid diagnostic tests in Iquitos, Peru and Phnom Penh, Cambodia.

PLoS Negl Trop Dis 2021 Apr 26;15(4):e0009307. Epub 2021 Apr 26.

Tulane School of Public Health and Tropical Medicine, New Orleans, Lousiana, United States of America.

Rapid diagnostic tests (RDTs) have the potential to identify infectious diseases quickly, minimize disease transmission, and could complement and improve surveillance and control of infectious and vector-borne diseases during outbreaks. The U.S. Defense Threat Reduction Agency's Joint Science and Technology Office (DTRA-JSTO) program set out to develop novel point-of-need RDTs for infectious diseases and deploy them for home use with no training. The aim of this formative study was to address two questions: 1) could community members in Iquitos, Peru and Phnom Penh, Cambodia competently use RDTs of different levels of complexity at home with visually based instructions provided, and 2) if an RDT were provided at no cost, would it be used at home if family members displayed febrile symptoms? Test kits with written and video (Peru only) instructions were provided to community members (Peru [n = 202]; Cambodia [n = 50]) or community health workers (Cambodia [n = 45]), and trained observers evaluated the competency level for each of the several steps required to successfully operate one of two multiplex RDTs on themselves or other consenting participant (i.e., family member). In Iquitos, >80% of residents were able to perform 11/12 steps and 7/15 steps for the two- and five-pathogen test, respectively. Competency in Phnom Penh never reached 80% for any of the 12 or 15 steps for either test; the percentage of participants able to perform a step ranged from 26-76% and 23-72%, for the two- and five-pathogen tests, respectively. Commercially available NS1 dengue rapid tests were distributed, at no cost, to households with confirmed exposure to dengue or Zika virus; of 14 febrile cases reported, six used the provided RDT. Our findings support the need for further implementation research on the appropriate level of instructions or training needed for diverse devices in different settings, as well as how to best integrate RDTs into existing local public health and disease surveillance programs at a large scale.
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http://dx.doi.org/10.1371/journal.pntd.0009307DOI Listing
April 2021

MALDI-TOF mass spectrometry for sub-typing of Streptococcus pneumoniae.

BMC Microbiol 2020 12 1;20(1):367. Epub 2020 Dec 1.

Cambodia Oxford Medical Research Unit, Angkor Hospital for Children, PO Box 50, Siem Reap, Cambodia.

Background: Serotyping of Streptococcus pneumoniae is important for monitoring of vaccine impact. Unfortunately, conventional and molecular serotyping is expensive and technically demanding. This study aimed to determine the ability of matrix-assisted laser desorption-ionisation time-of-flight (MALDI-TOF) mass spectrometry to discriminate between pneumococcal serotypes and genotypes (defined by global pneumococcal sequence cluster, GPSC). In this study, MALDI-TOF mass spectra were generated for a diverse panel of whole genome sequenced pneumococcal isolates using the bioMerieux VITEK MS in clinical diagnostic (IVD) mode. Discriminatory mass peaks were identified and hierarchical clustering was performed to visually assess discriminatory ability. Random forest and classification and regression tree (CART) algorithms were used to formally determine how well serotypes and genotypes were identified by MALDI-TOF mass spectrum.

Results: One hundred and ninety-nine pneumococci, comprising 16 serotypes and non-typeable isolates from 46 GPSC, were analysed. In the primary experiment, hierarchical clustering revealed poor congruence between MALDI-TOF mass spectrum and serotype. The correct serotype was identified from MALDI-TOF mass spectrum in just 14.6% (random forest) or 35.4% (CART) of 130 isolates. Restricting the dataset to the nine dominant GPSC (61 isolates / 13 serotypes), discriminatory ability improved slightly: the correct serotype was identified in 21.3% (random forest) and 41.0% (CART). Finally, analysis of 69 isolates of three dominant serotype-genotype pairs (6B-GPSC1, 19F-GPSC23, 23F-GPSC624) resulted in the correct serotype identification in 81.1% (random forest) and 94.2% (CART) of isolates.

Conclusions: This work suggests that MALDI-TOF is not a useful technique for determination of pneumococcal serotype. MALDI-TOF mass spectra appear more associated with isolate genotype, which may still have utility for future pneumococcal surveillance activities.
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http://dx.doi.org/10.1186/s12866-020-02052-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7709296PMC
December 2020

Detection of colonisation by extended-spectrum beta-lactamase or carbapenemase producing Enterobacterales from frozen stool specimens.

BMC Res Notes 2020 Sep 14;13(1):429. Epub 2020 Sep 14.

Cambodia Oxford Medical Research Unit, Angkor Hospital for Children, Siem Reap, Cambodia.

Objective: To determine the impact of pre-culture ultra-low temperature (ULT, - 80 °C) storage of human stool specimens on recovery of Extended-Spectrum Beta-Lactamase (ESBL) or Carbapenemase (CPM) producing Enterobacterales.

Results: Twenty stool specimens from a community-based household colonisation study in Cambodia were cultured fresh and after 4-5 days and ~ 6 months of ULT storage (as a slurry in tryptone soya broth-10% glycerol). Presumptive ESBL- and CPM-Escherichia coli isolates were detected in 19/20 (95%) and 1/20 (5%) freshly cultured specimens, respectively. The specimens yielded identical results when re-cultured after ULT storage at both time points. Detection of presumptive ESBL- and CPM-Klebsiella / Enterobacter / Citrobacter group was less frequent and slightly less stable over time. Comparison of antimicrobial susceptibility test profiles between pairs of E. coli and K. pneumoniae isolates from the two frozen culture time points revealed concordance in only 13/28 (46%) pairs, indicating likely colonisation by multiple strains. In conclusion, ULT storage of human stool specimens prior to culture appears to be an acceptable method for managing laboratory workflow in culture-based ESBL / CPM Enterobacterales colonisation studies in high prevalence settings.
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http://dx.doi.org/10.1186/s13104-020-05279-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7490871PMC
September 2020

Assessment of dual practice among physicians in Cambodia.

Hum Resour Health 2020 03 12;18(1):18. Epub 2020 Mar 12.

University of Health Sciences (UHS), 73, Monivong Blvd., Khan Daun Penh, Phnom Penh, Cambodia.

Background: Dual practice and multiple job holding are widespread among health workers throughout the world. Although dual practice can help the financially strained public sector retain skilled workers, there are also potential negative consequences if it is not regulated. In Cambodia, there is substantial anecdotal evidence of dual practice among physicians but there is very little data on the extent and prevalence of the practice. This study was conducted by the University of Health Sciences (UHS) to gain insight in to the employment practices of UHS alumni. Results from this survey may help to inform policymakers in rational planning for future health system development related to capacity building and regulation of human resources for health.

Methods: Data were collected from a self-administered survey of UHS graduates who graduated between 1999 and 2012. A total of 162 medical graduates were randomly sampled from a total of 1867 medical graduates between 1999 and 2012. Contacted individuals were asked to complete a written structured questionnaire regarding demographic characteristics, current employment and types of employment, compensation, and job satisfaction. The response rate of graduates sampled was 49% (79 completed questionnaires). The low response rate was primarily due to the difficulty in locating individuals.

Results: Of 79 respondents, 96% were currently employed at the time of the survey. However, only 63 of the respondents (80%) were working in the healthcare sector. The 16 respondents (20%) not working in healthcare were excluded from further analyses since they are not relevant to dual practice analysis. The vast majority (87%) of respondents are public sector employees (61.9% in public sector only and 25.4% in both public and private sector). 12.7% of respondents only work in the private sector. Almost half (47.6%) of respondents hold more than one job. For income satisfaction, physicians employed in both sectors have higher satisfaction than physicians employed in the public sector only.

Conclusions: As policymakers in Cambodia consider new approaches to regulation of the practice, it is important to know the context of the practice, the benefits to the healthcare system, and the costs. Recognizing the high prevalence of multiple job holding in Cambodia, as evidenced in our survey of UHS medical graduates, contributes to the discussion as important information that can be used toward meaningful reform.
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http://dx.doi.org/10.1186/s12960-020-0461-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7068863PMC
March 2020

Is enhancing the professionalism of healthcare providers critical to tackling antimicrobial resistance in low- and middle-income countries?

Hum Resour Health 2020 02 11;18(1):10. Epub 2020 Feb 11.

University of Health Sciences, Phnom Penh, Cambodia.

Background: Healthcare providers' (HCPs) professionalism refers to their commitment and ability to respond to the health needs of the communities they serve and to act in the best interest of patients. Despite attention to increasing the number of HCPs in low- and middle-income countries (LMIC), the quality of professional education delivered to HCPs and their resulting professionalism has been neglected. The Global Action Plan on Antimicrobial Resistance (AMR) seeks to reduce inappropriate use of antibiotics by urging patients to access antibiotics only through qualified HCPs, on the premise that qualified HCPs will act as more responsible and competent gatekeepers of access to antibiotics than unqualified HCPs.

Methods: We investigate whether weaknesses in HCP professionalism result in boundaries between qualified HCPs and unqualified providers being blurred, and how these weaknesses impact inappropriate provision of antibiotics by HCPs in two LMIC with increasing AMR-Pakistan and Cambodia. We conducted 85 in-depth interviews with HCPs, policymakers, and pharmaceutical industry representatives. Our thematic analysis was based on a conceptual framework of four components of professionalism and focused on identifying recurring findings in both countries.

Results: Despite many cultural and sociodemographic differences between Cambodia and Pakistan, there was a consistent finding that the behaviour of many qualified HCPs did not reflect their professional education. Our analysis identified five areas in which strengthening HCP education could enhance professionalism and reduce the inappropriate use of antibiotics: updating curricula to better cover the need for appropriate use of antibiotics; imparting stronger communication skills to manage patient demand for medications; inculcating essential professional ethics; building skills required for effective collaboration between doctors, pharmacists, and lay HCPs; and ensuring access to (unbiased) continuing medical education.

Conclusions: In light of the weaknesses in HCP professionalism identified, we conclude that global guidelines urging patients to only seek care at qualified HCPs should consider whether HCP professional education is equipping them to act in the best interest of the patient and society. Our findings suggest that improvements to HCP professional education are needed urgently and that these should focus not only on the curriculum content and learning methods, but also on the social purpose of graduates.
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http://dx.doi.org/10.1186/s12960-020-0452-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7014603PMC
February 2020

Machine-learning classification of neurocognitive performance in children with perinatal HIV initiating de novo antiretroviral therapy.

AIDS 2020 04;34(5):737-748

HIV Netherlands Australia Thailand (HIV-NAT) Research Collaboration, Thai Red Cross AIDS Research Center.

Objective: To develop a predictive model of neurocognitive trajectories in children with perinatal HIV (pHIV).

Design: Machine learning analysis of baseline and longitudinal predictors derived from clinical measures utilized in pediatric HIV.

Methods: Two hundred and eighty-five children (ages 2-14 years at baseline; Mage = 6.4 years) with pHIV in Southeast Asia underwent neurocognitive assessment at study enrollment and twice annually thereafter for an average of 5.4 years. Neurocognitive slopes were modeled to establish two subgroups [above (n = 145) and below average (n = 140) trajectories). Gradient-boosted multivariate regressions (GBM) with five-fold cross validation were conducted to examine baseline (pre-ART) and longitudinal predictive features derived from demographic, HIV disease, immune, mental health, and physical health indices (i.e. complete blood count [CBC]).

Results: The baseline GBM established a classifier of neurocognitive group designation with an average AUC of 79% built from HIV disease severity and immune markers. GBM analysis of longitudinal predictors with and without interactions improved the average AUC to 87 and 90%, respectively. Mental health problems and hematocrit levels also emerged as salient features in the longitudinal models, with novel interactions between mental health problems and both CD4 cell count and hematocrit levels. Average AUCs derived from each GBM model were higher than results obtained using logistic regression.

Conclusion: Our findings support the feasibility of machine learning to identify children with pHIV at risk for suboptimal neurocognitive development. Results also suggest that interactions between HIV disease and mental health problems are early antecedents to neurocognitive difficulties in later childhood among youth with pHIV.
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http://dx.doi.org/10.1097/QAD.0000000000002471DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7072001PMC
April 2020

Patients' and healthcare providers' perspectives of diabetes management in Cambodia: a qualitative study.

BMJ Open 2019 11 21;9(11):e032578. Epub 2019 Nov 21.

Epidemiology Domain, Saw Swee Hock School of Public Health, National University of Singapore, Singapore, Singapore.

Objective: This study aimed to explore the challenges encountered by patients and healthcare providers and opportunities for improvement in managing diabetes mellitus (DM) in a low- and middle-income country (LMIC) facing a rise in DM prevalence.

Design: Qualitative cross-sectional study.

Setting: Urban, semiurban, and rural areas in Cambodia.

Participants: Thirty health service providers and fifty-nine adult DM patients.

Results: Most of the 59 DM patients reported having developed DM complications when they first sought treatment. The biggest challenges for the patients were geographical barriers, diet control, and shortage of medication supply. The healthcare staff expressed concerns about their limited knowledge and lack of confidence to treat diabetes, limited availability of diabetes care services, inadequate laboratory services, shortage of staff, poor patients' compliance, and insufficient medication supplies. Both healthcare staff and patients urged an expansion of diabetes services in Cambodia and prioritisation of diabetes care in a manner similar to communicable disease control programmes of the recent past.

Conclusions: Currently, the Cambodian healthcare system has very limited capacity to provide quality care for chronic diseases. As a consequence, many patients are either left untreated or have interrupted care due to several barriers including financial, geographical, and lack of knowledge and skills. A more comprehensive and multipronged approach is urgently needed to improve DM care, which would require a collaborative effort from government, external funding agencies, private sector, and communities.
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http://dx.doi.org/10.1136/bmjopen-2019-032578DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6887069PMC
November 2019

Potential Use of Community-Based Rapid Diagnostic Tests for Febrile Illnesses: Formative Research in Peru and Cambodia.

PLoS Negl Trop Dis 2019 10 28;13(10):e0007773. Epub 2019 Oct 28.

University of California Fielding School of Public Health, Los Angeles, California, United States of America.

In 2012, the U.S. Defense Threat Reduction Agency Joint Science and Technology Office initiated a program to develop novel point-of-need diagnostic devices for surveillance of emerging infectious diseases including dengue, malaria, plague, and melioidosis. Prior to distribution of devices to observe their correct use among community members in Iquitos, Peru, and Phnom Penh, Cambodia, research was conducted to: 1) assess acceptability of use, including the motivation to use a rapid diagnostic test (RDT) before or instead of seeking care at a health facility, 2) explore comprehension of RDT use instructions, and 3) examine possible strategies for large scale RDT distribution and use at each site. In February 2014, 9 focus group discussions (FGD) with community members and 5 FGD with health professionals were conducted in Iquitos, and 9 FGD with community members and 9 in-depth interviews with health professionals in Phnom Penh. In both places, participants agreed to use the device themselves (involving finger prick) or could identify someone who could do so in their home or neighborhood. The main incentive to RDT use in both sites was the ability for device results to be used for care facilitation (post confirmatory tests), specifically reduced wait times to be seen or obtain a diagnosis. Comprehension of RDT use instructions was assessed in Iquitos by asking some participants to apply the device to research team members; after watching a short video, most steps were done correctly. In Phnom Penh, participants were asked to describe each step after reading the instructions; they struggled with comprehension. Health professionals' main concerns in both sites were their community's ability to accurately use the test, handle complicated instructions, and safety (i.e., disposal of lancets). Health system structure and ability to use home diagnostic devices varied in the two disease endemic sites, with substantial challenges in each, suggesting the need for different strategies for RDT large scale community use, and illustrating the value of formative research before deployment of novel technologies.
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http://dx.doi.org/10.1371/journal.pntd.0007773DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6837536PMC
October 2019

Invisible medicine sellers and their use of antibiotics: a qualitative study in Cambodia.

BMJ Glob Health 2019 20;4(5):e001787. Epub 2019 Sep 20.

Faculty of Public Health & Policy, London School of Hygiene & Tropical Medicine, London, UK.

Background: Global attention to antimicrobial resistance has increased interest in tackling the widespread inappropriate dispensing of antibiotics by informal, for-profit healthcare providers (HCPs). We provide new evidence on an understudied group of informal HCPs: invisible medicine sellers (IMS) who operate without any marked facility. We investigated factors that influence community decisions on which HCPs to purchase medicines from, focusing on reasons for using IMS, and compared different HCPs' knowledge of antibiotic use.

Methods: We conducted community focus group discussions (FGDs) in seven purposively selected villages representing high and low informal HCPs use in two peri-urban districts in Phnom Penh, Cambodia. Using information from the FGDs to identify HCPs that sell medicines, we interviewed 35 participants: 21 HCPs (including five IMS) and 14 key informants, including government HCPs and village leaders. We adopted an interpretative approach and conducted a thematic analysis.

Results: Community members typically knew of several formal and informal HCPs selling medicines nearby, and IMS were common, as were doctors that sell medicines covertly. Two factors were most salient in influencing the choice of HCP for medicine purchasing. The first was trust in the effectiveness of medicines provided, judged by the speed of symptomatic relief. This pushed HCPs to provide several medicines, including antibiotics, at the first consultation. The second was the convenience offered by IMS and other informal HCPs: supplying medicines when other facilities are closed, accepting delayed payments, providing incomplete courses of medication and selling human antibiotics for animal use.

Conclusion: This first study focusing on IMS indicates that it is important, but challenging, for public health agencies to engage with them to reduce inappropriate use of antibiotics. Although public health facilities must fill some gaps that informal HCPs are currently addressing, such as access to medicines at night, reducing demand for unnecessary antibiotics is also critical.
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http://dx.doi.org/10.1136/bmjgh-2019-001787DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6768357PMC
September 2019

Trajectory Analysis of Cognitive Outcomes in Children With Perinatal HIV.

Pediatr Infect Dis J 2019 10;38(10):1038-1044

Missouri Institute of Mental Health, University of Missouri-St. Louis, St. Louis, Missouri.

Background: Children with perinatal HIV (pHIV) may display distinct long-term cognitive phenotypes. We used group-based trajectory modeling to identify clusters of children with pHIV after similar developmental trajectories and predictors of belonging to select cognitive trajectory groups.

Methods: Participants included children, 4-17 years of age, with pHIV in Thailand and Cambodia. Cognitive measures included translated versions of Intelligence Quotient tests, Color Trails Tests and Beery-Buktenica Developmental Test of Visual-Motor Integration conducted semiannually over 3-6 years. The best fit of trajectory groups was determined using maximum likelihood estimation. Multivariate logistic regression identified baseline factors associated with belonging to the lowest scoring trajectory group.

Results: Group-based trajectory analyses revealed a 3-cluster classification for each cognitive test, labeled as high, medium and low scoring groups. Most trajectory group scores remained stable across age. Verbal IQ declined in all 3 trajectory groups and the high scoring group for Children's Color Trails Test 1 and 2 showed an increase in scores across age. Children in the lowest scoring trajectory group were more likely to present at an older age and report lower household income.

Conclusions: Group-based trajectory modeling succinctly classifies cohort heterogeneity in cognitive outcomes in pHIV. Most trajectories remained stable across age suggesting that cognitive potential is likely determined at an early age with the exception of a small subgroup of children who displayed developmental gains in select cognitive domains and may represent those with better cognitive reserve. Poverty and longer duration of untreated HIV may predispose children with pHIV to suboptimal cognitive development.
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http://dx.doi.org/10.1097/INF.0000000000002427DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6776249PMC
October 2019

Emotional and behavioral resilience among children with perinatally acquired HIV in Thailand and Cambodia.

AIDS 2019 06;33 Suppl 1:S17-S27

HIV Center for Clinical and Behavioral Studies, New York State Psychiatric Institute, Columbia University, New York, New York, USA.

Objectives: Psychosocial challenges associated with perinatally acquired HIV (PHIV) infection are well known, yet many children infected with HIV since birth demonstrate positive outcomes, referred to as resilience. The purpose of this study was to evaluate emotional-behavioral development and identify salient predictors of resilience among long-term survivors of PHIV.

Design: Prospective investigation of children with PHIV compared with demographically similar perinatally HIV-exposed but uninfected (PHEU) and HIV-unexposed, uninfected (HUU) children, all from Thailand and Cambodia.

Methods: The Child Behavior Checklist (CBCL; parent version) was administered at baseline and annual follow-up visits (median follow-up of 3 years) to children age 6-14. Resilience was defined as consistent CBCL scores on the Internalizing, Externalizing or Total Problem T scales within normative ranges (T-scores <60) at every time point. Generalized estimating equations examined CBCL scores over time and logistic models examined demographic, socioeconomic, and cultural predictors of resilience.

Results: Participants included 448 children (236 PHIV, 98 PHEU, 114 HUU), with median (interquartile range) age at first evaluation of 7 (6-9) years. Children with PHIV exhibited similar rates of resilience as PHEU and HUU on the Externalizing and Total Problems scales. Resilience on the Internalizing scale was more likely in PHEU (71%) compared with PHIV (59%) or HUU (56%), P = 0.049. Factors associated with resilience in adjusted models included: HIV-exposed but uninfected status, higher household income, Cambodian nationality, female sex, and caregiver type.

Conclusion: Despite biopsychosocial risks, resilience is observed among PHIV and PHEU children. Further study is needed to understand mechanisms underlying associated factors and intervention priorities.
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http://dx.doi.org/10.1097/QAD.0000000000002182DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7799438PMC
June 2019

Spatial and temporal projections of the prevalence of active tuberculosis in Cambodia.

BMJ Glob Health 2019 24;4(1):e001083. Epub 2019 Jan 24.

Saw Swee Hock School of Public Health, National University of Singapore and National University Health System, Singapore.

Introduction: Cambodia is among the 30 highest burden of tuberculosis (TB) countries. Active TB prevalence has been estimated using nationally representative multistage sampling that represents urban, rural and remote parts of the country, but the prevalence in non-sampled communes remains unknown. This study uses geospatial Bayesian statistics to estimate point prevalence across Cambodia, and demographic modelling that accounts for secular trends in fertility, mortality, urbanisation and prevalence rates to project the future burden of active TB.

Methods: A Bayesian hierarchical model was developed for the 2011 National Tuberculosis Prevalence survey to estimate the differential effect of age, sex and geographic stratum on active TB prevalence; these estimates were then married with high-resolution geographic information system layers to project prevalence across Cambodia. Future TB projections under alternative scenarios were then derived by interfacing these estimates with an individual-based demographic model.

Results: Strong differences in risk by age and sex, together with geographically varying population structures, yielded the first estimated prevalence map at a 1 km scale. The projected number of active TB cases within the catchment area of each existing government healthcare facility was derived, together with projections to the year 2030 under three scenarios: , and .

Conclusion: Synthesis of health and geographic data allows likely disease rates to be mapped at a high resolution to facilitate resource planning, while demographic modelling allows scenarios to be projected, demonstrating the need for the acceleration of control efforts to achieve a substantive impact on the future burden of TB in Cambodia.
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http://dx.doi.org/10.1136/bmjgh-2018-001083DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6347953PMC
January 2019

Positive Virological Outcomes of HIV-Infected Patients on Protease Inhibitor-Based Second-Line Regimen in Cambodia: The ANRS 12276 2PICAM Study.

Front Public Health 2018 19;6:63. Epub 2018 Mar 19.

University of Health Sciences (UHS), Phnom-Penh, Cambodia.

Background: Assessment of virological outcomes among HIV-infected patients receiving protease (PR) inhibitor-based second-line regimen are uncommon in Cambodia. The objective of this study is to assess the virological effectiveness of this regimen as well as impact of adherence boosting for patients experiencing virological failure.

Methods: The 2PICAM study (Clinicaltrial: NCT01801618) is a cross-sectional study of HIV-infected adults on PR inhibitor-based second-line regimen since at least 6 months, conducted in 13 representative sites, comprising more than 90% of the target population. Adults with HIV RNA above 250 copies/mL (threshold of the assay) at inclusion received boosted adherence counseling during 3 months followed by HIV RNA control. For confirmed virological failure, genotype resistance test was performed and expert committee used results for therapeutic decision.

Results: Among the 1,317 adults enrolled, the median duration of second-line regimen was 5 years. At inclusion, 1,182 (89.7%) patients achieved virological success (<250 copies/mL) and 135 (10.3%) experienced a virological failure (>250 copies/mL). In multivariable analysis, factors associated with virological success were: CD4 cell count between 201 and 350/mm (OR: 4.66, 95% CI: 2.57-8.47,  < 0.0001) and >350/mm (OR: 6.67, 95% CI: 4.02-11.06,  < 0.0001), duration of PI-based regimen >2 years (OR: 1.64, 95% CI: 1.03-2.62,  = 0.037), ATV-containing regimen (0R: 1.65, 95% CI: 1.04-2.63,  = 0.034) and high level of adherence (OR: 2.41, 95% CI: 1.07-5.41,  = 0.033). After adherence counseling, 63 (46.7%) patients were rescued while 72 (53.3%) were not. For the 54 patients with genotype resistance tests available, high or intermediate levels of resistance to lopinavir, atazanavir, and darunavir were reported for 13 (24%), 12 (22.2%), and 2 (3.7%) patients, respectively. Change to an alternative PR inhibitor-based regimen was recommended for 17 patients and to third-line regimen, including integrase inhibitors for 12.

Conclusion: This study reports high rate of virological suppression of second-line regimen and importance of adherence boosting prior to deciding any change of ART regimen. Genotype resistance tests appear necessary to guide decisions. Such information was of great importance for National HIV Program to adapt guidelines and program needs for third-line regimen.
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http://dx.doi.org/10.3389/fpubh.2018.00063DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5890147PMC
March 2018

Serotype Distribution of Clinical Isolates before the Introduction of the 13-Valent Pneumococcal Conjugate Vaccine in Cambodia.

Am J Trop Med Hyg 2018 03 4;98(3):791-796. Epub 2018 Jan 4.

Institut Pasteur du Cambodge, Phnom Penh, Cambodia.

Childhood vaccination with the 13-valent pneumococcal conjugate vaccine (PCV13) was introduced in Cambodia in January 2015. Baseline data regarding circulating serotypes are scarce. All microbiology laboratories in Cambodia were contacted for identification of stored isolates of from clinical specimens taken before the introduction of PCV13. Available isolates were serotyped using a multiplex polymerase chain reaction method. Among 166 identified isolates available for serotyping from patients with pneumococcal disease, 4% were isolated from upper respiratory samples and 80% were from lower respiratory samples, and 16% were invasive isolates. PCV13 serotypes accounted for 60% (95% confidence interval [CI] 52-67) of all isolates; 56% (95% CI 48-64) of noninvasive and 77% (95% CI 57-89) of invasive isolates. Antibiotic resistance was more common among PCV13 serotypes. This study of clinical isolates supports the potential for high reduction in pneumococcal disease burden and may serve as baseline data for future monitoring of serotypes circulation after implementation of PCV13 childhood vaccination in Cambodia.
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http://dx.doi.org/10.4269/ajtmh.17-0692DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5930902PMC
March 2018

Youth paying for sex: what are the associated factors? Findings from a cross-sectional study in Cambodia.

BMC Public Health 2018 01 8;18(1):113. Epub 2018 Jan 8.

Center for Global Health Research, College of Education and Health Sciences, Touro University California, Vallejo, USA.

Background: At-risk male youth in Cambodia who purchase sex are at greater risk for HIV compared to the general population. Factors associated with paying for sex among youth are poorly studied, both globally and in Cambodia. This study aimed to identify specific factors associated with transactional sex with women among most-at-risk male youth in Cambodia.

Methods: This cross-sectional questionnaire survey was conducted with 405 sexually active male youth aged 16-24 recruited at 'hotspots' in the capital city of Phnom Penh and seven provinces. We collected data on demographic factors, sexual behaviors, HIV testing and other potential factors. Multivariable logistic regression analysis was used to identify factors associated with transactional sex.

Results: In total, this study included 405 male youth with a mean age of 21.3 (SD = 2.2). Of the total respondents, 82.5% (n = 334) have ever paid for sex. After controlling for potential confounding, participants who purchased sex in the last 12 months remained significantly more likely to be older than 18 (AOR = 3.60, 95% CI = 1.26-10.62), reside in an urban area (AOR = 2.29, 95% CI = 1.24-4.20), never have been married (AOR = 9.58, 95% CI = 4.34-21.12), spend less than 2.55 USD per day (AOR = 2.22, 95% CI = 1.12-4.40), and have had more than 4.6 sexual partners in the past year (AOR = 16.73, 95% CI = 4.71-59.36).

Conclusions: This study highlights the high proportion of Cambodian male youth who paid for sex and the potential challenges to addressing this issue. While the majority of HIV prevention interventions surrounding sex work are aimed at female sex workers themselves, targeting the demand side of sex work, particularly the local demand, may be an important next step towards a sustainable HIV prevention.
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http://dx.doi.org/10.1186/s12889-017-4999-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5759259PMC
January 2018

Cognition, Emotional Health, and Immunological Markers in Children With Long-Term Nonprogressive HIV.

J Acquir Immune Defic Syndr 2018 04;77(4):417-426

HIV Netherlands Australia Thailand (HIV-NAT) Research Collaboration, Thai Red Cross AIDS Research Center, Bangkok, Thailand.

Background: HIV-infected children with long-term nonprogressive (LTNP) disease eventually convert to a progressive disease type, yet the extent to which these children experience the cognitive and emotional symptoms observed in typical progressive HIV (Progressors) is unknown.

Methods: Eighty-eight LTNPs, 53 Progressors, and 323 healthy controls completed annual assessments of cognitive and emotional health as part of a prospective study. The 2 HIV-infected groups and the healthy controls were matched on age and sex distribution at enrollment. Plasma HIV RNA, T-cell counts/percentages, activated monocytes, perivascular monocytes, and markers of macrophage activation (sCD163 and sCD14) were compared by progression subtype. Cognitive and emotional outcomes were compared using cross-sectional linear regression analysis and longitudinal sensitivity models.

Results: LTNPs exhibited the same cognitive phenotype and emotional dysregulation as Progressors, with worse outcomes in both groups compared with controls. In addition, cognitive and emotional symptoms were evident before children reached the minimum age for LTNP designation (8 years). Baseline plasma HIV RNA, sCD163, activated monocytes, and perivascular monocytes were lower in LTNPs versus Progressors, with no difference in T-cell counts/percentages or sCD14 levels. Most LTNPs converted to a progressive disease subtype during the study, with similar cognitive and emotion profiles between these subgroups.

Conclusions: Pediatric LTNPs experience cognitive and emotional difficulties that mirror symptoms of progressive disease. The abnormalities are present at young ages and persist independent of plasma T-cell counts. The findings highlight the neurodevelopmental risk of pediatric HIV, even in those with early innate disease control.
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http://dx.doi.org/10.1097/QAI.0000000000001619DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5825279PMC
April 2018

Massive Iatrogenic Outbreak of Human Immunodeficiency Virus Type 1 in Rural Cambodia, 2014-2015.

Clin Infect Dis 2018 05;66(11):1733-1741

University of Health Sciences, Phnom Penh, Cambodia.

Background: In 2014-2015, 242 individuals aged 2-89 years were newly diagnosed with human immunodeficiency virus type 1 (HIV-1) in Roka, a rural commune in Cambodia. A case-control study attributed the outbreak to unsafe injections. We aimed to reconstruct the likely transmission history of the outbreak.

Methods: We assessed in 209 (86.4%) HIV-infected cases the presence of hepatitis C virus (HCV) and hepatitis B virus (HBV). We identified recent infections using antibody (Ab) avidity testing for HIV and HCV. We performed amplification, sequencing, and evolutionary phylogenetic analyses of viral strains. Geographical coordinates and parenteral exposure through medical services provided by an unlicensed healthcare practitioner were obtained from 193 cases and 1499 controls during interviews.

Results: Cases were coinfected with HCV (78.5%) and HBV (12.9%). We identified 79 (37.8%) recent (<130 days) HIV infections. Phylogeny of 202 HIV env C2V3 sequences showed a 198-sample CRF01_AE strains cluster, with time to most recent common ancestor (tMRCA) in September 2013 (95% highest posterior density, August 2012-July 2014), and a peak of 15 infections/day in September 2014. Three geospatial HIV hotspots were discernible in Roka and correlated with high exposure to the practitioner (P = .04). Fifty-nine of 153 (38.6%) tested cases showed recent (<180 days) HCV infections. Ninety HCV NS5B sequences formed 3 main clades, 1 containing 34 subtypes 1b with tMRCA in 2012, and 2 with 51 subtypes 6e and tMRCAs in 2002-2003.

Conclusions: Unsafe injections in Cambodia most likely led to an explosive iatrogenic spreading of HIV, associated with a long-standing and more genetically diverse HCV propagation.
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http://dx.doi.org/10.1093/cid/cix1071DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5963970PMC
May 2018

Adherence to PI-based 2nd-line regimens in Cambodia is not simply a question of individual behaviour: the ANRS 12276 2PICAM study.

Trop Med Int Health 2017 11 2;22(11):1428-1435. Epub 2017 Oct 2.

Aix Marseille Univ, INSERM, IRD, SESSTIM, Sciences Economiques & Sociales de la Santé et Traitement de l'Information Médicale, Marseille, France.

Objectives: To investigate whether adherence to antiretroviral treatment (ART) can be explained not only by individual factors but also by health care facilities' characteristics, among a sample of people living with HIV (PLWH) treated with PI-based regimens in Cambodia.

Methods: The ANRS 12276 2PICAM cross-sectional survey was conducted between February 2013 and April 2014 among PLWH followed up in 13 health care facilities. The 1316 patients in this analysis corresponded to 90% of the total number of adult patients treated with 2nd-line PI-based regimens in Cambodia in the study period. A variable indicating whether patients were non-adherent (=1) or completely adherent (=0) was constructed. Health care facilities and individual characteristics were included in a two-level logistic model to investigate their influence on patients' adherence to ART.

Results: A total of 17% of participants did not adhere to ART. Patients in health care facilities outside the capital Phnom Penh were six times more likely to be non-adherent than those treated in health care facilities in the capital (OR: 6.15, 95% CI [1.47, 25.79]). Providing psychosocial care (provided by psychologist counsellors and/or full-time coaches) was found to be a structural facilitator of adherence, as the probability of non-adherence fell by 38.5% per each additional psychological worker present in health care facilities (OR: 0.62, 95% CI [0.43, 0.89]). Financial constraints were the main individual factor preventing adherence.

Conclusions: Our results suggest that inefficiencies in health care delivery are detrimental to PLWH health and to the exceptional progress currently being made by Cambodia in response to HIV. Policy makers should focus on increasing the number of psychosocial workers, especially in areas outside the capital.
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http://dx.doi.org/10.1111/tmi.12975DOI Listing
November 2017

HIV-infected children in the Asia-Pacific region with baseline severe anemia: antiretroviral therapy and outcomes.

Asian Biomed (Res Rev News) 2016 Jun;10(3):229-234

The Kirby Institute, University of New South Wales, Sydney, NSW 2052, Australia.

Background: Severe anemia is common among children infected with human immunodeficiency virus (HIV). The choice of antiretroviral (ART) regimen needs careful consideration. No information is available regarding the initial ART regimens used in the Asia-Pacific region and the rate of switch of ART regimens in HIV-infected children with severe anemia.

Objectives: To study the initial ART regimens and the rate of switch of ART regimens used during the first 36 months in HIV-infected children with severe anemia and to evaluate their clinical and laboratory outcomes.

Methods: We analyzed regional cohort data of 130 Asian children aged <18 years with baseline severe anemia (hemoglobin <7.5 g/dl) who started antiretroviral therapy (ART) between January 2003 and September 2013.

Results: At ART initiation, median age was 3.5 years old (interquartile range (IQR) 1.7 to 6.3) and median hemoglobin was 6.7 g/dL (IQR 5.9-7.1, range 3.0-7.4). Initial ART regimens included stavudine (85.4%), zidovudine (13.8%), and abacavir (0.8%). In 81 children with available hemoglobin data after 6 months of ART, 90% recovered from severe anemia with a median hemoglobin of 10.7 g/dL (IQR 9.6-11.7, range 4.4-13.5). Those starting AZT-based ART had a mortality rate of 10.8 (95% confidence interval (CI) 4.8-23.9) per 100 patient-years compared to 2.7 (95% CI 1.6-4.6) per 100 patient-years among those who started d4T-based ART.

Conclusions: With the phase-out of stavudine, age-appropriate non-zidovudine options are needed for younger Asian children with severe anemia.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5321077PMC
June 2016

Cluster of HIV Infections Associated With Unsafe Injection Practices in a Rural Village in Cambodia.

J Acquir Immune Defic Syndr 2017 Jul;75(3):e82-e86

*University of Health Sciences, Phnom Penh, Cambodia †World Health Organization, Phnom Penh, Cambodia ‡Cambodian National Center for HIV/AIDS, Dermatology and Sexually Transmitted Diseases, Ministry of Health, Phnom Penh, Cambodia §Centers for Disease Control and Prevention, Cambodia Office, Phnom Penh, Cambodia ‖HIV/Hepatitis Unit, Institut Pasteur du Cambodge, Phnom Penh, Cambodia ¶KHANA, Phnom Penh, Cambodia #World Health Organization, Regional Office for the Western Pacific, Manila, Philippines.

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http://dx.doi.org/10.1097/QAI.0000000000001295DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6814627PMC
July 2017

Less research on tuberculosis than HIV and malaria when research agendas are poorly coordinated: a systematic review of research outputs from Cambodia.

Int J Infect Dis 2017 Mar 12;56:25-29. Epub 2016 Dec 12.

London School of Hygiene and Tropical Medicine, Keppel St, London WC1E 7HT, UK; Mahidol University, Ratchathewi District, Bangkok, Thailand.

Objective: Coordination of health interventions and research is often weak during periods of political transition and unprecedented aid inflows, which Cambodia has recently experienced. Although HIV, tuberculosis (TB), and malaria have been a focus of international funding, TB has received much less. This study compares the numbers and methodologies of studies conducted on TB, malaria, and HIV in Cambodia, identifying evidence gaps and future research needs.

Methods: Three electronic databases and the grey literature were searched for studies on HIV, TB, and malaria published between January 2000 and October 2015. Information about the disease focus and methodology was extracted from the studies included.

Results: A total of 2581 unique studies were screened and 712 were included in the analysis. The results of this review demonstrated that despite increasing numbers of publications, there have been fewer studies on TB (16%) than HIV (43%) and malaria (41%). Observational epidemiological studies outnumbered other methodologies (44%) for all three diseases.

Conclusions: Despite substantial investments, important research areas appear to have been neglected in Cambodia; specifically, studies on TB and studies involving economic, qualitative, interventional, and genomics methods. The inter-disease disparity in published research in Cambodia identified, considered alongside disease burden, suggests that an increase in TB research may be needed to inform control strategies.
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http://dx.doi.org/10.1016/j.ijid.2016.11.417DOI Listing
March 2017

Renal Dysfunction during Tenofovir Use in a Regional Cohort of HIV-Infected Individuals in the Asia-Pacific.

PLoS One 2016 25;11(8):e0161562. Epub 2016 Aug 25.

TREAT Asia, amfAR - The Foundation for AIDS Research, Bangkok, Thailand.

Background: In resource-limited settings, routine monitoring of renal function during antiretroviral therapy (ART) has not been recommended. However, concerns for tenofovir disoproxil fumarate (TDF)-related nephrotoxicity persist with increased use.

Methods: We investigated serum creatinine (S-Cr) monitoring rates before and during ART and the incidence and prevalence of renal dysfunction after starting TDF by using data from a regional cohort of HIV-infected individuals in the Asia-Pacific. Time to renal dysfunction was defined as time from TDF initiation to the decline in estimated glomerular filtration rate (eGFR) to <60 ml/min/1.73m2 with >30% reduction from baseline using the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation or the decision to stop TDF for reported TDF-nephrotoxicity. Predictors of S-Cr monitoring rates were assessed by Poisson regression and risk factors for developing renal dysfunction were assessed by Cox regression.

Results: Among 2,425 patients who received TDF, S-Cr monitoring rates increased from 1.01 to 1.84 per person per year after starting TDF (incidence rate ratio 1.68, 95%CI 1.62-1.74, p <0.001). Renal dysfunction on TDF occurred in 103 patients over 5,368 person-years of TDF use (4.2%; incidence 1.75 per 100 person-years). Risk factors for developing renal dysfunction included older age (>50 vs. ≤30, hazard ratio [HR] 5.39, 95%CI 2.52-11.50, p <0.001; and using PI-based regimen (HR 1.93, 95%CI 1.22-3.07, p = 0.005). Having an eGFR prior to TDF (pre-TDF eGFR) of ≥60 ml/min/1.73m2 showed a protective effect (HR 0.38, 95%CI, 0.17-0.85, p = 0.018).

Conclusions: Renal dysfunction on commencing TDF use was not common, however, older age, lower baseline eGFR and PI-based ART were associated with higher risk of renal dysfunction during TDF use in adult HIV-infected individuals in the Asia-Pacific region.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0161562PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4999237PMC
August 2017

Effects of unplanned treatment interruptions on HIV treatment failure - results from TAHOD.

Trop Med Int Health 2016 May 29;21(5):662-74. Epub 2016 Mar 29.

YRGCARE Medical Centre, Chennai, India.

Objectives: 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.

Methods: Patients initiating cART between 2006 and 2013 were included. TI was defined as stopping cART for >1 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 P < 0.10 in univariable analyses were included in multivariable analyses, where P < 0.05 was considered statistically significant.

Results: 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, interruptions >30 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); and >365 days HR = 9.10, 95% CI (4.27-19.38), all P < 0.001, compared to 0-14 days). Reasons for previous TI were not statistically significant (P = 0.158).

Conclusions: 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.
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http://dx.doi.org/10.1111/tmi.12690DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4959847PMC
May 2016

Hepatitis B and C Co-Infection in HIV Patients from the TREAT Asia HIV Observational Database: Analysis of Risk Factors and Survival.

PLoS One 2016 2;11(3):e0150512. Epub 2016 Mar 2.

Center for Infectious Disease and Cancer Research, Kaohsiung Medical University, Kaohsiung, Taiwan.

Background: We assessed the effects of hepatitis B (HBV) or hepatitis C (HCV) co-infection on outcomes of antiretroviral therapy (ART) in HIV-infected patients enrolled in the TREAT Asia HIV Observational Database (TAHOD), a multi-center cohort of HIV-infected patients in the Asia-Pacific region.

Methods: Patients testing HBs antigen (Ag) or HCV antibody (Ab) positive within enrollment into TAHOD were considered HBV or HCV co-infected. Factors associated with HBV and/or HCV co-infection were assessed by logistic regression models. Factors associated with post-ART HIV immunological response (CD4 change after six months) and virological response (HIV RNA <400 copies/ml after 12 months) were also determined. Survival was assessed by the Kaplan-Meier method and log rank test.

Results: A total of 7,455 subjects were recruited by December 2012. Of patients tested, 591/5656 (10.4%) were HBsAg positive, 794/5215 (15.2%) were HCVAb positive, and 88/4966 (1.8%) were positive for both markers. In multivariate analysis, HCV co-infection, age, route of HIV infection, baseline CD4 count, baseline HIV RNA, and HIV-1 subtype were associated with immunological recovery. Age, route of HIV infection, baseline CD4 count, baseline HIV RNA, ART regimen, prior ART and HIV-1 subtype, but not HBV or HCV co-infection, affected HIV RNA suppression. Risk factors affecting mortality included HCV co-infection, age, CDC stage, baseline CD4 count, baseline HIV RNA and prior mono/dual ART. Shortest survival was seen in subjects who were both HBV- and HCV-positive.

Conclusion: In this Asian cohort of HIV-infected patients, HCV co-infection, but not HBV co-infection, was associated with lower CD4 cell recovery after ART and increased mortality.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0150512PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4774987PMC
July 2016

Cluster of HIV Infections Attributed to Unsafe Injection Practices--Cambodia, December 1, 2014-February 28, 2015.

MMWR Morb Mortal Wkly Rep 2016 Feb 19;65(6):142-5. Epub 2016 Feb 19.

In December 2014, local health authorities in Battambang province in northwest Cambodia reported 30 cases of human immunodeficiency virus (HIV) infection in a rural commune (district subdivision) where only four cases had been reported during the preceding year. The majority of cases occurred in residents of Roka commune. The Cambodian National Center for HIV/AIDS (acquired immunodeficiency syndrome), Dermatology and Sexually Transmitted Diseases (NCHADS) investigated the outbreak in collaboration with the University of Health Sciences in Phnom Penh and members of the Roka Cluster Investigation Team. By February 28, 2015, NCHADS had confirmed 242 cases of HIV infection among the 8,893 commune residents, an infection rate of 2.7%. Molecular investigation of the HIV strains present in this outbreak indicated that the majority of cases were linked to a single HIV strain that spread quickly within this community. An NCHADS case-control study identified medical injections and infusions as the most likely modes of transmission. In response to this outbreak, the Government of Cambodia has taken measures to encourage safe injection practices by licensed medical professionals, ban unlicensed medical practitioners, increase local capacity for HIV testing and counseling, and expand access to HIV treatment in Battambang province. Measures to reduce the demand for unnecessary medical injections and the provision of unsafe injections are needed. Estimates of national HIV incidence and prevalence might need to be adjusted to account for unsafe injection as a risk exposure.
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http://dx.doi.org/10.15585/mmwr.mm6506a2DOI Listing
February 2016

Antiretroviral Therapy in Severely Malnourished, HIV-infected Children in Asia.

Pediatr Infect Dis J 2016 May;35(5):e144-51

From the *The Kirby Institute, UNSW Australia, Sydney, Australia; †Department of Pediatrics, Faculty of Medicine, Chiang Mai University and Research Institute for Health Sciences, Chiang Mai, Thailand; ‡Cipto Mangunkusumo General Hospital, Jakarta, Indonesia; §Hospital Likas, Kota Kinabalu, Malaysia; ¶Division of Infectious Diseases, Department of Pediatrics, Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand; ‖National Centre for HIV/AIDS Dermatology and STDs, Phnom Penh, Cambodia; **Children's Hospital 1, Ho Chi Minh City, Vietnam; ††Chiangrai Prachanukroh Hospital, Chiang Rai, Thailand; ‡‡National Hospital of Pediatrics, Hanoi, Vietnam; §§Children's Hospital 2, Ho Chi Minh City, Vietnam; ¶¶HIV-NAT, the Thai Red Cross AIDS Research Centre, Bangkok, Thailand; ‖‖Department of Pediatrics, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand; ***Hospital Raja Perempuan Zainab II, Kelantan, Malaysia; †††YRGCARE Medical Centre, CART CRS, Chennai, India; ‡‡‡Sanglah Hospital, Udayana University, Bali, Indonesia; §§§Pediatric Institute, Hospital Kuala Lumpur, Kuala Lumpur, Malaysia; and ¶¶¶Members of TREAT Asia Pediatric HIV Observational Database are listed in Appendix.

Background: Information on antiretroviral therapy (ART) use in HIV-infected children with severe malnutrition (SM) is lacking. We investigated long-term ART outcomes in this population.

Methods: Children enrolled in the TREAT Asia Pediatric HIV Observational Database who had SM (weight-for-height or body mass index-for-age Z score less than -3) at ART initiation were analyzed. Generalized estimating equations were used to investigate poor weight recovery (weight-for-age Z score less than -3) and poor CD4% recovery (CD4% <25), and competing risk regression was used to analyze mortality and toxicity-associated treatment modification.

Results: Three hundred fifty-five (11.9%) of 2993 children starting ART had SM. Their median weight-for-age Z score increased from -5.6 at ART initiation to -2.3 after 36 months. Not using trimethoprim-sulfamethoxazole prophylaxis at baseline was associated with poor weight recovery [odds ratio: 2.49 vs. using; 95% confidence interval (CI): 1.66-3.74; P < 0.001]. Median CD4% increased from 3.0 at ART initiation to 27.2 after 36 months, and 56 (15.3%) children died during follow-up. More profound SM was associated with poor CD4% recovery (odds ratio: 1.78 for Z score less than -4.5 vs. -3.5 to less than -3.0; 95% CI: 1.08-2.92; P = 0.023) and mortality (hazard ratio: 2.57 for Z score less than -4.5 vs. -3.5 to less than -3.0; 95% CI: 1.24-5.33; P = 0.011). Twenty-two toxicity-associated ART modifications occurred at a rate of 2.4 per 100 patient-years, and rates did not differ by malnutrition severity.

Conclusion: Trimethoprim-sulfamethoxazole prophylaxis is important for the recovery of weight-for-age in severely malnourished children starting ART. The extent of SM does not impede weight-for-age recovery or antiretroviral tolerability, but CD4% response is compromised in children with a very low weight-for-height/body mass index-for-age Z score, which may contribute to their high rate of mortality.
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http://dx.doi.org/10.1097/INF.0000000000001074DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4829479PMC
May 2016

Non-Nucleoside Reverse Transcriptase Inhibitor-Based Antiretroviral Therapy in Perinatally HIV-Infected, Treatment-Naïve Adolescents in Asia.

J Adolesc Health 2016 Apr 20;58(4):451-459. Epub 2016 Jan 20.

Faculty of Medicine, The Kirby Institute, UNSW Australia, Sydney, New South Wales, Australia.

Purpose: About a third of untreated, perinatally HIV-infected children reach adolescence. We evaluated the durability and effectiveness of non-nucleoside reverse-transcriptase inhibitor (NNRTI)-based antiretroviral therapy (ART) in this population.

Methods: Data from perinatally HIV-infected, antiretroviral-naïve patients initiated on NNRTI-based ART aged 10-19 years who had ≥6 months of follow-up were analyzed. Competing risk regression was used to assess predictors of NNRTI substitution and clinical failure (World Health Organization Stage 3/4 event or death). Viral suppression was defined as a viral load <400 copies/mL.

Results: Data from 534 adolescents met our inclusion criteria (56.2% female; median age at treatment initiation 11.8 years). After 5 years of treatment, median height-for-age z score increased from -2.3 to -1.6, and median CD4+ cell count increased from 131 to 580 cells/mm(3). The proportion of patients with viral suppression after 6 months was 87.6% and remained >80% up to 5 years of follow-up. NNRTI substitution and clinical failure occurred at rates of 4.9 and 1.4 events per 100 patient-years, respectively. Not using cotrimoxazole prophylaxis at ART initiation was associated with NNRTI substitution (hazard ratio [HR], 1.5 vs. using; 95% confidence interval [CI] = 1.0-2.2; p = .05). Baseline CD4+ count ≤200 cells/mm(3) (HR, 3.3 vs. >200; 95% CI = 1.2-8.9; p = .02) and not using cotrimoxazole prophylaxis at ART initiation (HR, 2.1 vs. using; 95% CI = 1.0-4.6; p = .05) were both associated with clinical failure.

Conclusions: Despite late ART initiation, adolescents achieved good rates of catch-up growth, CD4+ count recovery, and virological suppression. Earlier ART initiation and routine cotrimoxazole prophylaxis in this population may help to reduce current rates of NNRTI substitution and clinical failure.
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http://dx.doi.org/10.1016/j.jadohealth.2015.11.006DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4808326PMC
April 2016

Final Height and Associated Factors in Perinatally HIV-infected Asian Adolescents.

Pediatr Infect Dis J 2016 Feb;35(2):201-4

From the *HIV-NAT, the Thai Red Cross AIDS Research Centre, Bangkok, Thailand; †The Kirby Institute, University of New South Wales, Sydney, Australia; ‡Research Institute for Health Sciences, Chiang Mai University, Chiang Mai, Thailand; §Department of Pediatrics, Siriraj Hospital, Mahidol University, Bangkok, Thailand; ¶Chiangrai Prachanukroh Hospital, Chiang Rai, Thailand; ‖Division of Infectious Diseases, Department of Pediatrics, Khon Kaen University, Khon Kaen, Thailand; **Research Unit, National Centre for HIV/AIDS, Dermatology and STDs, Phnom Penh, Cambodia; ††Department of Public Health, University of Health Sciences, Phnom Penh, Cambodia; ‡‡Pediatric TB/HIV/AIDS Care Department, National Pediatric Hospital, Phnom Penh, Cambodia; §§YR Gaitonde Centre for AIDS Research and Education, Chennai, India; ¶¶Department of Pediatrics, Penang Hospital, Penang, Malaysia; ‖‖Infectious Disease Department, National Hospital of Pediatrics, Hanoi, Vietnam; ***Department of Pediatrics, Hospital Raja Perempuan Zainab II, Kelantan, Malaysia; †††TREAT Asia/amfAR, The Foundation for AIDS Research, Bangkok, Thailand; and ‡‡‡Department of Pediatrics, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand.

We analyzed final height of 273 perinatally HIV-infected Asian adolescents older than 18 years at their last clinic visit. By the World Health Organization child growth reference, 30% were stunted, but by the Thai child growth reference, 19% were stunted. Half of those who were stunted at antiretroviral therapy initiation remained stunted over time. Being male and having a low baseline height-for-age Z score of less than -1.0 were associated with low final height Z score.
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http://dx.doi.org/10.1097/INF.0000000000000961DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4712093PMC
February 2016

Factors associated with sex work among at-risk female youth in Cambodia: a cross-sectional study.

AIDS Care 2016 19;28(3):339-46. Epub 2015 Oct 19.

a Public Health Program, College of Education and Health Sciences , Touro University California, Vallejo , CA , USA.

In Cambodia, despite great achievements in reducing the prevalence of HIV in the general population, reducing new HIV infections among young at-risk women remains a challenge. This study was designed to examine the prevalence of risky behaviors of sexually active female youth in Cambodia and to explore risk factors associated with engagement in transactional sex. We surveyed sexually active female youth aged 10-24 enrolled at risk "hotspots" in eight provinces in Cambodia. We collected data on demographic factors, sexual behavior, and factors hypothesized to be associated with transactional sex. Multivariable logistic regression was used to identify associations between demographic and sexual behavior and transactional sex. Of the 280 respondents, the mean age was 21.2, and 48.1% had been paid for sex in the past year. After adjustment, at-risk females who were never have been married (adjusted odds ratio (AOR) 3.40, 95% confidence interval (CI) = 1.65-6.97), have completed less than 6 years of school (AOR 3.26, 95% CI = 1.60-6.66), have 1 or more parents who had died (AOR 4.34, 95% CI = 2.00-9.38), be a heavy alcohol drinker (AOR 3.58, 95% CI = 1.78-7.18), have used a condom with their boyfriend during last sexual encounter (AOR 3.50, 95% CI = 1.68-7.32), and have ever had an HIV test (AOR 3.51, 95% CI = 1.68-7.32) were more likely to engage in sex work. Our findings suggest that prevention strategies for female youth at risk of engagement in sex work should include upstream structural interventions that aim to encourage girls' education and empowerment. In addition, tailored sex education and behavior change messaging about the risks of heavy drinking, condom use with romantic partners, and the importance of frequent HIV testing for at-risk youth and sex workers should be designed and delivered to youth currently engaging in sex work.
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http://dx.doi.org/10.1080/09540121.2015.1096893DOI Listing
September 2016

Late Presentation into Care of HIV Disease and Its Associated Factors in Asia: Results of TAHOD.

AIDS Res Hum Retroviruses 2016 Mar 15;32(3):255-61. Epub 2015 Oct 15.

1 Department of Internal Medicine and AIDS Research Institute, Yonsei University College of Medicine , Seoul, Korea.

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 <200 cells/μl or an AIDS-defining event within ±3 months of first positive HIV test) were analyzed in a random effects logistic regression model. Among 3,744 patients, 2,681 (72%) were late presenters. In the multivariable model, older patients were more likely to be late presenters than younger (≤30 years) patients [31-40, 41-50, and ≥51 years: odds ratio (OR) = 1.57, 95% confidence interval (CI) 1.31-1.88; OR = 2.01, 95% CI 1.58-2.56; and OR = 1.69, 95% CI 1.23-2.31, respectively; all p ≤ 0.001]. Injecting drug users (IDU) were more likely (OR = 2.15, 95% CI 1.42-3.27, p < 0.001) and those with homosexual HIV exposure were less likely (OR = 0.45, 95% CI 0.35-0.58, p < 0.001) to be late presenters compared to those with heterosexual HIV exposure. Females were less likely to be late presenters (OR = 0.44, 95% CI 0.36-0.53, p < 0.001). The year of first positive HIV test was not associated with late presentation. Efforts to reduce the patients who first seek HIV care at the late stage are needed. The identified risk factors associated with late presentation should be utilized in formulating targeted public health intervention to improve earlier entry into HIV care.
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http://dx.doi.org/10.1089/AID.2015.0058DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4779961PMC
March 2016