Displaying publications 21 - 40 of 307 in total

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  1. Al-Darraji H, Hill P, Sharples K, Altice FL, Kamarulzaman A
    Int J Prison Health, 2023 Jan 11.
    PMID: 36622107 DOI: 10.1108/IJPH-01-2022-0001
    PURPOSE: This intensified case finding study aimed to evaluate the prevalence of tuberculosis (TB) disease among people with HIV entering the largest prison in Malaysia.

    DESIGN/METHODOLOGY/APPROACH: The study was conducted in Kajang prison, starting in July 2013 in the men's prison and June 2015 in the women's prison. Individuals tested positive for HIV infection, during the mandatory HIV testing at the prison entry, were consecutively recruited over five months at each prison. Consented participants were interviewed using a structured questionnaire and asked to submit two sputum samples that were assessed using GeneXpert MTB/RIF (Xpert) and culture, irrespective of clinical presentation. Factors associated with active TB (defined as a positive result on either Xpert or culture) were assessed using regression analyses.

    FINDINGS: Overall, 214 incarcerated people with HIV were recruited. Most were men (84.6%), Malaysians (84.1%) and people who inject drugs (67.8%). The mean age was 37.5 (SD 8.2) years, and median CD4 lymphocyte count was 376 cells/mL (IQR 232-526). Overall, 27 (12.6%) TB cases were identified, which was independently associated with scores of five or more on the World Health Organization clinical scoring system for prisons (ARR 2.90 [95% CI 1.48-5.68]).

    ORIGINALITY/VALUE: Limited data exists about the prevalence of TB disease at prison entry, globally and none from Malaysia. The reported high prevalence of TB disease in the study adds an important and highly needed information to design comprehensive TB control programmes in prisons.

  2. Mohd Sani N, Aziz Z, Kamarulzaman A
    BioDrugs, 2023 Jan;37(1):109-120.
    PMID: 36571697 DOI: 10.1007/s40259-022-00571-5
    BACKGROUND: With the increasing availability biosimilars, the role of pharmacists as drug information specialists has expanded to include promoting biosimilar acceptance among prescribers.

    OBJECTIVES: Our study aimed to determine Malaysian hospital pharmacists' perspectives on biosimilars and to identify factors influencing the successful promotion of biosimilars to prescribers.

    METHODS: This was a cross-sectional, web-based survey of hospital pharmacists across Malaysia. Multivariate logistic regression analysis was used to identify factors associated with pharmacists successfully promoting biosimilar use.

    RESULTS: Of the 913 responses, over 60% of pharmacists believed that patients may safely be switched from the originator product to a biosimilar and would have the same clinical outcome. Many lacked training in biosimilars (62.8%); yet most (80.6%) perceived pharmacists to play a critical role in promoting biosimilar prescribing. Multivariate logistic regression analysis showed that the strongest factor associated with pharmacists' successful promotion of biosimilars to prescribers was having confidence (odds ratio [OR], 3.33; 95% confidence interval [CI] 2.10-5.26). Respondents who had prior experience handling biosimilars were more likely to be successful in promoting biosimilar use than those without (OR, 1.76; 95% CI 1.16-2.66). The pharmacists' top perceived barrier to promote biosimilars in clinical practice was efficacy concerns.

    CONCLUSION: Although Malaysian pharmacists are in favour of biosimilars, they lack training to promote biosimilar use. Among the factors associated with successful promotion of biosimilars to prescribers are pharmacist confidence, their previous experience handling biosimilars, and prior biosimilar training.

  3. Ni Z, Shrestha R, Earnshaw VA, Tee YC, Altice FL, Azwa I, et al.
    LGBT Health, 2023;10(2):169-175.
    PMID: 36251945 DOI: 10.1089/lgbt.2021.0452
    Purpose: Gay, bisexual, and other men who have sex with men (MSM) experience high levels of stigma and discrimination. Minimizing the stigma and discrimination is critical to fostering an inclusive environment for care and optimizing health outcomes. This study aimed at exploring the factors related to physicians' intention to discriminate against MSM in Malaysia. Methods: Physicians (N = 542) from two university-affiliated hospitals in Kuala Lumpur, Malaysia, completed an online cross-sectional survey between January and March 2016. Measures included sociodemographic and clinical characteristics, intention to discriminate against MSM, and several stigma-related constructs. Bivariate and multivariable linear regressions were used to evaluate independent correlates of discrimination intent against MSM. Results: Physicians' intention to discriminate against MSM was low (mean [M] = 1.9, standard deviation [SD] = 0.7), but most physicians (70.6%) had a mean score greater than 1.0, indicating that most physicians expressed some degree of intention to discriminate against MSM. A minority of physicians (10.7%), however, had a score of 3.0 or higher, revealing some physicians holding a moderate to high level of discrimination intent toward MSM. The multivariable model demonstrated that physicians who expressed greater prejudice (B = 0.30, p 
  4. Woodward M, Ramasubramanian V, Kamarulzaman A, Tantawichien T, Wang M, Song JY, et al.
    Clin Interv Aging, 2023;18:869-880.
    PMID: 37284594 DOI: 10.2147/CIA.S406601
    The impact of vaccinating the older population against vaccine-preventable diseases in terms of health, social and economic benefits has been increasingly recognised. However, there is a gap in the utilisation of vaccines worldwide. The population is ageing at an unprecedented pace in the Asia-Pacific (APAC) region, with the number of persons older than 65 years set to double by 2050 to around 1.3 billion. More than 18% of the population in Japan, Hong Kong, and China is over the age of 65 years. This highlights the importance of prioritising resources to address societal obligations toward the needs of the ageing generation. This review provides an overview of the challenges to adult vaccination in APAC, drivers to increase vaccination coverage, vaccination insights gained through the COVID-19 pandemic, and potential measures to increase the uptake of adult vaccines in the region.
  5. Tackett S, Jenn Ng C, Sugarman J, Daniel EGS, Gopalan N, Tivyashinee, et al.
    Ethics Hum Res, 2023;45(3):29-39.
    PMID: 37167475 DOI: 10.1002/eahr.500166
    Educational programs are integral to building health research ethics (HRE) capacity, but no outcomes framework exists to guide them. We empirically developed a competency framework for health research ethics education-the Framework for Research Ethics Studies Competencies and Outcomes (FRESCO)-using mixed methods, including group concept mapping and a survey of international experts. FRESCO includes seven competency domains: (1) Foundational Knowledge; (2) Laws, Regulations, Guidelines, and Policies for Research Oversight; (3) Ethical-Issue Identification, Analysis, and Resolution; (4) Engagement, Communication, and Advocacy; (5) Lifelong Learning, Education, Research, and Scholarship; (6) Coordination, Stewardship, and Responsiveness in HRE Systems; and (7) Impartiality, Honesty, and Responsibility. These domains are detailed in 27 subdomains. Survey respondents rated FRESCO's relevance to HRE highly. FRESCO can be adapted and implemented in educational programs to refine recruitment and selection processes, educational and assessment methods, and performance measures to ensure that HRE educational programs have their intended effects.
  6. Shrestha R, Wickersham JA, Khati A, Azwa I, Ni Z, Kamarulzaman A, et al.
    JMIR Res Protoc, 2022 Dec 21;11(12):e43318.
    PMID: 36542425 DOI: 10.2196/43318
    BACKGROUND: Men who have sex with men (MSM) are disproportionately affected by the HIV epidemic in Malaysia and globally. Cross-cutting prevention strategies such as mobile health (mHealth), particularly smartphone apps, hold great promise for HIV prevention efforts among Malaysian MSM, especially when linked to HIV testing and pre-exposure prophylaxis (PrEP).

    OBJECTIVE: This study aims to adapt an existing app to create and test a clinic-integrated app (JomPrEP), a virtual platform to deliver HIV testing and PrEP services for MSM in Malaysia.

    METHODS: The JomPrEP project involves developing and testing an app-based platform for HIV prevention among Malaysian MSM and will be conducted in 2 phases. In phase I (development phase), we will adapt an existing mHealth app (HealthMindr) to create a new clinic-integrated app called "JomPrEP" to deliver holistic HIV prevention services (eg, HIV testing, PrEP, support services for mental health and substance use) among MSM in Malaysia. During phase II (testing phase), we will use a type I hybrid implementation science trial design to test the efficacy of JomPrEP while gathering information on implementation factors to guide future scale-up in real-world settings.

    RESULTS: As of September 2022, we have completed phase I of the proposed study. Based on a series of formative work completed during phase I, we developed a fully functional, clinic-integrated JomPrEP app, which provides a virtual platform for MSM in Malaysia to facilitate their engagement in HIV prevention in a fast and convenient manner. Based on participant feedback provided during phase I, we are currently optimizing JomPrEP and the research protocols for a large-scale efficacy trial (phase II), which will commence in January 2023.

    CONCLUSIONS: Scant HIV prevention resources coupled with entrenched stigma, discrimination, and criminalization of same-sex sexual behavior and substance use hamper access to HIV prevention services in Malaysia. If found efficacious, JomPrEP can be easily adapted for a range of health outcomes and health care delivery services for MSM, including adaptation to other low- and middle-income countries.

    TRIAL REGISTRATION: ClinicalTrials.gov NCT05325476; https://clinicaltrials.gov/ct2/show/NCT05325476.

    INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/43318.

  7. Gatechompol S, Kittanamongkolchai W, Ketloy C, Prompetchara E, Thitithanyanont A, Jongkaewwattana A, et al.
    Nat Microbiol, 2022 Dec;7(12):1987-1995.
    PMID: 36376393 DOI: 10.1038/s41564-022-01271-0
    Effective mRNA SARS-CoV-2 vaccines are available but need to be stored in freezers, limiting their use to countries that have appropriate storage capacity. ChulaCov19 is a prefusion non-stabilized SARS-CoV-2 spike-protein-encoding, nucleoside-modified mRNA, lipid nanoparticle encapsulated vaccine that we report to be stable when stored at 2-8 °C for up to 3 months. Here we report safety and immunogenicity data from a phase I open-label, dose escalation, first-in-human trial of the ChulaCov19 vaccine (NCT04566276). Seventy-two eligible volunteers, 36 of whom were aged 18-55 (adults) and 36 aged 56-75 (elderly), were enroled. Two doses of vaccine were administered 21 d apart at 10, 25 or 50 μg per dose (12 per group). The primary outcome was safety and the secondary outcome was immunogenicity. All three dosages of ChulaCov19 were well tolerated and elicited robust dose-dependent and age-dependent B- and T-cell responses. Transient mild/moderate injection site pain, fever, chills, fatigue and headache were more common after the second dose. Four weeks after the second dose, in the adult cohort, MicroVNT-50 geometric mean titre against wild-type SARS-CoV-2 was 848 (95% CI, 483-1,489), 736 (459-1,183) and 1,140 (854-1,522) IU ml-1 at 10, 25 and 50 μg doses, respectively, versus 285 (196-413) IU ml-1 for human convalescent sera. All dose levels elicited 100% seroconversion, with geometric mean titre ratios 4-8-fold higher than for human convalescent sera (P 
  8. Bazazi AR, Culbert GJ, Wegman MP, Heimer R, Kamarulzaman A, Altice FL
    BMC Infect Dis, 2022 Nov 11;22(1):837.
    PMID: 36368939 DOI: 10.1186/s12879-022-07804-6
    INTRODUCTION: Mortality is elevated after prison release and may be higher in people with HIV and opioid use disorder (OUD). Maintenance with opioid agonist therapy (OAT) like methadone or buprenorphine reduces mortality in people with OUD and may confer benefits to people with OUD and HIV leaving prison. Survival benefits of OAT, however, have not been evaluated prospectively in people with OUD and HIV leaving prison.

    METHODS: This study prospectively evaluated mortality after prison release and whether methadone initiated before release increased survival after release in a sample of men with HIV and OUD (n = 291). We linked national death records to data from a controlled trial of prerelease methadone initiation conducted from 2010 to 2014 with men with HIV and OUD imprisoned in Malaysia. Vital statistics were collected through 2015. Allocation to prerelease methadone was by randomization (n = 64) and participant choice (n = 246). Cox proportional hazards models were used to estimate treatment effects of prerelease methadone on postrelease survival.

    RESULTS: Overall, 62 deaths occurred over 872.5 person-years (PY) of postrelease follow-up, a crude mortality rate of 71.1 deaths per 1000 PY (95% confidence interval [CI] 54.5-89.4). Most deaths were of infectious etiology, mostly related to HIV. In a modified intention-to-treat analysis, the impact of prerelease methadone on postrelease mortality was consistent with a null effect in unadjusted (hazard ratio [HR] 1.3, 95% CI 0.6-3.1) and covariate-adjusted (HR 1.2, 95% CI 0.5-2.8) models. Predictors of mortality were educational level (HR 1.4, 95% CI 1.0-1.8), pre-incarceration alcohol use (HR 2.0, 95% CI 1.1-3.9), and lower CD4+ T-lymphocyte count (HR 0.8 per 100-cell/mL increase, 95% CI 0.7-1.0).

    CONCLUSIONS: Postrelease mortality in this sample of men with HIV and OUD was extraordinarily high, and most deaths were likely of infectious etiology. No effect of prerelease methadone on postrelease mortality was observed, which may be due to study limitations or an epidemiological context in which inadequately treated HIV, and not inadequately treated OUD, is the main cause of death after prison release.

    TRIAL REGISTRATION: NCT02396979. Retrospectively registered 24/03/2015.

  9. Chan YT, Cheong HC, Tang TF, Rajasuriar R, Cheng KK, Looi CY, et al.
    Biomedicines, 2022 Nov 04;10(11).
    PMID: 36359329 DOI: 10.3390/biomedicines10112809
    The progressive decline of CD8+ cytotoxic T cells in human immunodeficiency virus (HIV)-infected patients due to infection-triggered cell exhaustion and cell death is significantly correlated with disease severity and progression into the life-threatening acquired immunodeficiency syndrome (AIDS) stage. T cell exhaustion is a condition of cell dysfunction despite antigen engagement, characterized by augmented surface expression of immune checkpoint molecules such as programmed cell death protein 1 (PD-1), which suppress T cell receptor (TCR) signaling and negatively impact the proliferative and effector activities of T cells. T cell function is tightly modulated by cellular glucose metabolism, which produces adequate energy to support a robust reaction when battling pathogen infection. The transition of the T cells from an active to an exhausted state following pathogen persistence involves a drastic change in metabolic activity. This review highlights the interplay between immune checkpoint molecules and glucose metabolism that contributes to T cell exhaustion in the context of chronic HIV infection, which could deliver an insight into the rational design of a novel therapeutic strategy.
  10. Isbell M, Bekker LG, Grinsztejn B, Kates J, Kamarulzaman A, Lewin SR, et al.
    BMJ Glob Health, 2022 Nov;7(11).
    PMID: 36446447 DOI: 10.1136/bmjgh-2022-010854
  11. Rupasinghe D, Choi JY, Yunihastuti E, Kiertiburanakul S, Ross J, Ly PS, et al.
    J Med Virol, 2022 Nov;94(11):5451-5464.
    PMID: 35869413 DOI: 10.1002/jmv.28019
    Liver disease is a growing burden among people living with HIV (PLHIV) in resource-limited settings. As an indicator of liver disease, risk factors of high alanine aminotransferase (ALT) and cirrhosis were assessed among PLHIV in the TREAT Asia HIV Observational Database (TAHOD). Patients on combination antiretroviral therapy (cART) with a pre-cART ALT measurement and at least one follow-up ALT measurement were included. Factors associated with high ALT (ALT levels > 5 times its upper limit of normal) were analyzed using repeated measure logistic regression over a 10-year follow-up period. Liver cirrhosis was defined as having an AST to Platelet Ratio Index score > 1.5, fibrosis-4 score > 3.25, or a clinical diagnosis of cirrhosis. Cox regression analysis stratified by site was used to analyze factors associated with cirrhosis among those in follow-up after 2015. Of 5182 patients, 101 patients (1.9%) had high ALT levels with hepatitis C virus (HCV) antibody positive (odds ratio [OR]: 4.98, 95% confidence interval [CI]: 2.82-8.77, p 
  12. Lazarus JV, Romero D, Kopka CJ, Karim SA, Abu-Raddad LJ, Almeida G, et al.
    Nature, 2022 Nov;611(7935):332-345.
    PMID: 36329272 DOI: 10.1038/s41586-022-05398-2
    Despite notable scientific and medical advances, broader political, socioeconomic and behavioural factors continue to undercut the response to the COVID-19 pandemic1,2. Here we convened, as part of this Delphi study, a diverse, multidisciplinary panel of 386 academic, health, non-governmental organization, government and other experts in COVID-19 response from 112 countries and territories to recommend specific actions to end this persistent global threat to public health. The panel developed a set of 41 consensus statements and 57 recommendations to governments, health systems, industry and other key stakeholders across six domains: communication; health systems; vaccination; prevention; treatment and care; and inequities. In the wake of nearly three years of fragmented global and national responses, it is instructive to note that three of the highest-ranked recommendations call for the adoption of whole-of-society and whole-of-government approaches1, while maintaining proven prevention measures using a vaccines-plus approach2 that employs a range of public health and financial support measures to complement vaccination. Other recommendations with at least 99% combined agreement advise governments and other stakeholders to improve communication, rebuild public trust and engage communities3 in the management of pandemic responses. The findings of the study, which have been further endorsed by 184 organizations globally, include points of unanimous agreement, as well as six recommendations with >5% disagreement, that provide health and social policy actions to address inadequacies in the pandemic response and help to bring this public health threat to an end.
  13. Kamarulzaman A, Ramnarayan K, Mocumbi AO
    Lancet, 2022 Oct 29;400(10362):1492-1494.
    PMID: 36522198 DOI: 10.1016/S0140-6736(22)02087-6
  14. Peng ML, Wickersham JA, Altice FL, Shrestha R, Azwa I, Zhou X, et al.
    JMIR Form Res, 2022 Oct 06;6(10):e42055.
    PMID: 36201390 DOI: 10.2196/42055
    BACKGROUND: Mobile technologies are being increasingly developed to support the practice of medicine, nursing, and public health, including HIV testing and prevention. Chatbots using artificial intelligence (AI) are novel mobile health strategies that can promote HIV testing and prevention among men who have sex with men (MSM) in Malaysia, a hard-to-reach population at elevated risk of HIV, yet little is known about the features that are important to this key population.

    OBJECTIVE: The aim of this study was to identify the barriers to and facilitators of Malaysian MSM's acceptance of an AI chatbot designed to assist in HIV testing and prevention in relation to its perceived benefits, limitations, and preferred features among potential users.

    METHODS: We conducted 5 structured web-based focus group interviews with 31 MSM in Malaysia between July 2021 and September 2021. The interviews were first recorded, transcribed, coded, and thematically analyzed using NVivo (version 9; QSR International). Subsequently, the unified theory of acceptance and use of technology was used to guide data analysis to map emerging themes related to the barriers to and facilitators of chatbot acceptance onto its 4 domains: performance expectancy, effort expectancy, facilitating conditions, and social influence.

    RESULTS: Multiple barriers and facilitators influencing MSM's acceptance of an AI chatbot were identified for each domain. Performance expectancy (ie, the perceived usefulness of the AI chatbot) was influenced by MSM's concerns about the AI chatbot's ability to deliver accurate information, its effectiveness in information dissemination and problem-solving, and its ability to provide emotional support and raise health awareness. Convenience, cost, and technical errors influenced the AI chatbot's effort expectancy (ie, the perceived ease of use). Efficient linkage to health care professionals and HIV self-testing was reported as a facilitating condition of MSM's receptiveness to using an AI chatbot to access HIV testing. Participants stated that social influence (ie, sociopolitical climate) factors influencing the acceptance of mobile technology that addressed HIV in Malaysia included privacy concerns, pervasive stigma against homosexuality, and the criminalization of same-sex sexual behaviors. Key design strategies that could enhance MSM's acceptance of an HIV prevention AI chatbot included an anonymous user setting; embedding the chatbot in MSM-friendly web-based platforms; and providing user-guiding questions and options related to HIV testing, prevention, and treatment.

    CONCLUSIONS: This study provides important insights into key features and potential implementation strategies central to designing an AI chatbot as a culturally sensitive digital health tool to prevent stigmatized health conditions in vulnerable and systematically marginalized populations. Such features not only are crucial to designing effective user-centered and culturally situated mobile health interventions for MSM in Malaysia but also illuminate the importance of incorporating social stigma considerations into health technology implementation strategies.

  15. Shrestha R, Maviglia F, Altice FL, DiDomizio E, Khati A, Mistler C, et al.
    J Med Internet Res, 2022 Jul 25;24(7):e36917.
    PMID: 35877172 DOI: 10.2196/36917
    BACKGROUND: The growth in mobile technology access, utilization, and services holds great promise in facilitating HIV prevention efforts through mobile health (mHealth) interventions in Malaysia. Despite these promising trends, there is a dearth of evidence on the use of mHealth platforms that addresses HIV prevention among Malaysian men who have sex with men.

    OBJECTIVE: The goal of this study was to gain insight into (1) access and utilization of communication technology (eg, landline phone, internet, mobile phone), (2) acceptability of mHealth-based interventions for HIV prevention services, and (3) preferences regarding the format and frequency of mHealth interventions among Malaysian men who have sex with men.

    METHODS: We conducted a cross-sectional survey with Malaysian men who have sex with men between July 2018 and March 2020. Participants were recruited using respondent-driven sampling in the Greater Kuala Lumpur region of Malaysia. We collected information on demographic characteristics, HIV risk-related behaviors, access to and the frequency of use of communication technology, and acceptability of using mHealth for HIV prevention using a self-administered questionnaire with a 5-point scale (1, never; 2, rarely; 3, sometimes; 4, often; 5, all the time).

    RESULTS: A total of 376 men participated in the survey. Almost all respondents owned or had access to a smartphone with internet access (368/376, 97.9%) and accessed the internet daily (373/376, 99.2%), mainly on a smartphone (334/376, 88.8%). Participants on average used smartphones primarily for social networking (mean 4.5, SD 0.8), followed by sending or receiving emails (mean 4.0, SD 1.0), and searching for health-related information (mean 3.5, SD 0.9). There was high acceptance of the use of mHealth for HIV prevention (mean 4.1, SD 1.5), including for receiving HIV prevention information (345/376, 91.8%), receiving medication reminders (336/376, 89.4%), screening and monitoring sexual activity (306/376, 81.4%) or illicit drug use (281/376, 74.7%), and monitoring drug cravings (280/376, 74.5%). Participants overwhelmingly preferred a smartphone app over other modalities (eg, text, phone call, email) for engaging in mHealth HIV prevention tools. Preference for app notifications ranged from 186/336 (53.9%), for receiving HIV prevention information, to 212/336 (69.3%), for screening and monitoring sexual activity. Acceptance of mHealth was higher for those who were university graduates (P=.003), living in a relationship with a partner (P=.04), engaged in sexualized drug use (P=.01), and engaged in receptive anal sex (P=.006).

    CONCLUSIONS: Findings from this study provide support for developing and deploying mHealth strategies for HIV prevention using a smartphone app in men who have sex with men-a key population with suboptimal engagement in HIV prevention and treatment.

  16. Tackett S, Sugarman J, Ng CJ, Kamarulzaman A, Ali J
    J Med Ethics, 2022 Jun;48(6):391-396.
    PMID: 33811112 DOI: 10.1136/medethics-2021-107237
    Health research ethics (HRE) training programmes are being developed and implemented globally, often with a goal of increasing local capacity to assure ethical conduct in health-related research. Yet what it means for there to be sufficient HRE capacity is not well-defined, and there is currently no consensus on outcomes that HRE training programmes should collectively intend to achieve. Without defining the expected outcomes, meaningful evaluation of individual participants and programmes is challenging. In this article, we briefly describe the evolution of formal education in HRE, articulate the need for a framework to define outcomes for HRE training programmes, and provide guidance for developing HRE competency frameworks that define outcomes suited to their contexts. We detail critical questions for developing HRE competency frameworks using a six-step process: (1) define the purposes, intended uses and scope of the framework; (2) describe the context in which practice occurs; (3) gather data using a variety of methods to inform the competency framework; (4) translate the data into competencies that can be used in educational programmes; (5) report on the competency development process and results and (6) evaluate and update the competency framework. We suggest that competency frameworks should be feasible to develop using this process, and such efforts promise to contribute to programmatic advancement.
  17. Dhana A, Hamada Y, Kengne AP, Kerkhoff AD, Rangaka MX, Kredo T, et al.
    Lancet Infect Dis, 2022 Apr;22(4):507-518.
    PMID: 34800394 DOI: 10.1016/S1473-3099(21)00387-X
    BACKGROUND: The WHO-recommended tuberculosis screening and diagnostic algorithm in ambulatory people living with HIV is a four-symptom screen (known as the WHO-recommended four symptom screen [W4SS]) followed by a WHO-recommended molecular rapid diagnostic test (eg Xpert MTB/RIF [hereafter referred to as Xpert]) if W4SS is positive. To inform updated WHO guidelines, we aimed to assess the diagnostic accuracy of alternative screening tests and strategies for tuberculosis in this population.

    METHODS: In this systematic review and individual participant data meta-analysis, we updated a search of PubMed (MEDLINE), Embase, the Cochrane Library, and conference abstracts for publications from Jan 1, 2011, to March 12, 2018, done in a previous systematic review to include the period up to Aug 2, 2019. We screened the reference lists of identified pieces and contacted experts in the field. We included prospective cross-sectional, observational studies and randomised trials among adult and adolescent (age ≥10 years) ambulatory people living with HIV, irrespective of signs and symptoms of tuberculosis. We extracted study-level data using a standardised data extraction form, and we requested individual participant data from study authors. We aimed to compare the W4SS with alternative screening tests and strategies and the WHO-recommended algorithm (ie, W4SS followed by Xpert) with Xpert for all in terms of diagnostic accuracy (sensitivity and specificity), overall and in key subgroups (eg, by antiretroviral therapy [ART] status). The reference standard was culture. This study is registered with PROSPERO, CRD42020155895.

    FINDINGS: We identified 25 studies, and obtained data from 22 studies (including 15 666 participants; 4347 [27·7%] of 15 663 participants with data were on ART). W4SS sensitivity was 82% (95% CI 72-89) and specificity was 42% (29-57). C-reactive protein (≥10 mg/L) had similar sensitivity to (77% [61-88]), but higher specificity (74% [61-83]; n=3571) than, W4SS. Cough (lasting ≥2 weeks), haemoglobin (<10 g/dL), body-mass index (<18·5 kg/m2), and lymphadenopathy had high specificities (80-90%) but low sensitivities (29-43%). The WHO-recommended algorithm had a sensitivity of 58% (50-66) and a specificity of 99% (98-100); Xpert for all had a sensitivity of 68% (57-76) and a specificity of 99% (98-99). In the one study that assessed both, the sensitivity of sputum Xpert Ultra was higher than sputum Xpert (73% [62-81] vs 57% [47-67]) and specificities were similar (98% [96-98] vs 99% [98-100]). Among outpatients on ART (4309 [99·1%] of 4347 people on ART), W4SS sensitivity was 53% (35-71) and specificity was 71% (51-85). In this population, a parallel strategy (two tests done at the same time) of W4SS with any chest x-ray abnormality had higher sensitivity (89% [70-97]) and lower specificity (33% [17-54]; n=2670) than W4SS alone; at a tuberculosis prevalence of 5%, this strategy would require 379 more rapid diagnostic tests per 1000 people living with HIV than W4SS but detect 18 more tuberculosis cases. Among outpatients not on ART (11 160 [71·8%] of 15 541 outpatients), W4SS sensitivity was 85% (76-91) and specificity was 37% (25-51). C-reactive protein (≥10 mg/L) alone had a similar sensitivity to (83% [79-86]), but higher specificity (67% [60-73]; n=3187) than, W4SS and a sequential strategy (both test positive) of W4SS then C-reactive protein (≥5 mg/L) had a similar sensitivity to (84% [75-90]), but higher specificity than (64% [57-71]; n=3187), W4SS alone; at 10% tuberculosis prevalence, these strategies would require 272 and 244 fewer rapid diagnostic tests per 1000 people living with HIV than W4SS but miss two and one more tuberculosis cases, respectively.

    INTERPRETATION: C-reactive protein reduces the need for further rapid diagnostic tests without compromising sensitivity and has been included in the updated WHO tuberculosis screening guidelines. However, C-reactive protein data were scarce for outpatients on ART, necessitating future research regarding the utility of C-reactive protein in this group. Chest x-ray can be useful in outpatients on ART when combined with W4SS. The WHO-recommended algorithm has suboptimal sensitivity; Xpert for all offers slight sensitivity gains and would have major resource implications.

    FUNDING: World Health Organization.

  18. Stoicescu C, Lataire Q, Peters K, Amon JJ, Kamarulzaman A, Ali R, et al.
    Lancet, 2022 01 29;399(10323):419-421.
    PMID: 35032436 DOI: 10.1016/S0140-6736(22)00003-4
  19. Han F, Gulam MY, Zheng Y, Zulhaimi NS, Sia WR, He D, et al.
    Front Immunol, 2022;13:985385.
    PMID: 36341446 DOI: 10.3389/fimmu.2022.985385
    MAIT cells are persistently depleted and functionally exhausted in HIV-1-infected patients despite long-term combination antiretroviral therapy (cART). IL-7 treatment supports MAIT cell reconstitution in vivo HIV-1-infected individuals and rescues their functionality in vitro. Single-nucleotide polymorphisms (SNPs) of the IL-7RA gene modulate the levels of soluble(s)IL-7Rα (sCD127) levels and influence bioavailability of circulating IL-7. Here we evaluate the potential influence of IL-7RA polymorphisms on MAIT cell numbers and function in healthy control (HC) subjects and HIV-1-infected individuals on long-term cART. Our findings indicate that IL-7RA haplotype 2 (H2*T), defined as T-allele carriers at the tagging SNP rs6897932, affects the size of the peripheral blood MAIT cell pool, as well as their production of cytokines and cytolytic effector proteins in response to bacterial stimulation. H2*T carriers had lower sIL-7Rα levels and higher MAIT cell frequency with enhanced functionality linked to higher expression of MAIT cell-associated transcription factors. Despite an average of 7 years on suppressive cART, MAIT cell levels and function in HIV-1-infected individuals were still significantly lower than those of HC. Notably, we observed a significant correlation between MAIT cell levels and cART duration only in HIV-1-infected individuals carrying IL-7RA haplotype 2. Interestingly, treatment with sIL-7Rα in vitro suppressed IL-7-dependent MAIT cell proliferation and function following cognate stimulations. These observations suggest that sIL-7Rα levels may influence MAIT cell numbers and function in vivo by limiting IL-7 bioavailability to MAIT cells. Collectively, these observations suggest that IL-7RA polymorphisms may play a significant role in MAIT cell biology and influence MAIT cells recovery in HIV-1 infection. The potential links between IL7RA polymorphisms, MAIT cell immunobiology, and HIV-1 infection warrant further studies going forward.
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