Project description:BackgroundTuberculosis (TB) is the most common cause of death in people living with HIV (PLHIV), yet TB often goes undiagnosed since many patients are not able to produce a sputum specimen, and traditional diagnostics are costly or unavailable. A novel, rapid lateral flow assay, Fujifilm SILVAMP TB LAM (SILVAMP-LAM), detects the presence of TB lipoarabinomannan (LAM) in urine, and is substantially more sensitive for diagnosing TB in PLHIV than an earlier LAM assay (Alere Determine TB LAM lateral flow assay [LF-LAM]). Here, we present an individual participant data meta-analysis of the diagnostic accuracy of SILVAMP-LAM in adult PLHIV, including both published and unpublished data.Methods and findingsAdult PLHIV (≥18 years) were assessed in 5 prospective cohort studies in South Africa (3 cohorts), Vietnam, and Ghana, carried out during 2012 to 2017. Of the 1,595 PLHIV who met eligibility criteria, the majority (61%) were inpatients, median age was 37 years (IQR 30-43), 43% had a CD4 count ≤ 100 cells/μl, and 35% were receiving antiretroviral therapy. Most participants (94%) had a positive WHO symptom screen for TB on enrollment, and 45% were diagnosed with microbiologically confirmed TB, using mycobacterial culture or Xpert MTB/RIF testing of sputum, urine, or blood. Previously published data from inpatients were combined with unpublished data from outpatients. Biobanked urine samples were tested, using blinded double reading, with SILVAMP-LAM and LF-LAM. Applying a microbiological reference standard for assessment of sensitivity, the overall sensitivity for TB detection was 70.7% (95% CI 59.0%-80.8%) for SILVAMP-LAM compared to 34.9% (95% CI 19.5%-50.9%) for LF-LAM. Using a composite reference standard (which included patients with both microbiologically confirmed as well as clinically diagnosed TB), SILVAMP-LAM sensitivity was 65.8% (95% CI 55.9%-74.6%), and that of LF-LAM 31.4% (95% CI 19.1%-43.7%). In patients with CD4 count ≤ 100 cells/μl, SILVAMP-LAM sensitivity was 87.1% (95% CI 79.3%-93.6%), compared to 56.0% (95% CI 43.9%-64.9%) for LF-LAM. In patients with CD4 count 101-200 cells/μl, SILVAMP-LAM sensitivity was 62.7% (95% CI 52.4%-71.9%), compared to 25.3% (95% CI 15.8%-34.9%) for LF-LAM. In those with CD4 count > 200 cells/μl, SILVAMP-LAM sensitivity was 43.9% (95% CI 34.3%-53.9%), compared to 10.9% (95% CI 5.2%-18.4%) for LF-LAM. Using a microbiological reference standard, the specificity of SILVAMP-LAM was 90.9% (95% CI 87.2%-93.7%), and that of LF-LAM 95.3% (95% CI 92.2%-97.7%). Limitations of this study include the use of biobanked, rather than fresh urine samples, and testing by skilled laboratory technicians in research laboratories, rather than at the point of care.ConclusionsIn this study, we found that SILVAMP-LAM identified a substantially higher proportion of TB patients in PLHIV than LF-LAM. The sensitivity of SILVAMP-LAM was highest in patients with CD4 count ≤ 100 cells/μl. Further work is needed to demonstrate accuracy when implemented as a point-of-care test.

Project description:BackgroundSymptom-based screening for tuberculosis is recommended for all people living with HIV. This recommendation results in unnecessary Xpert MTB/RIF testing in many individuals living in tuberculosis-endemic areas and thus poor implementation of intensified case finding and tuberculosis preventive therapy. Novel approaches to tuberculosis screening are needed to help achieve global targets for tuberculosis elimination. We assessed the performance of C-reactive protein (CRP) measured with a point-of-care assay as a screening tool for active pulmonary tuberculosis.MethodsFor this prospective study, we enrolled adults (aged ≥18 years) living with HIV with CD4 cell count less than or equal to 350 cells per μL who were initiating antiretroviral therapy (ART) from two HIV/AIDS clinics in Uganda. CRP concentrations were measured at study entry with a point-of-care assay using whole blood obtained by fingerprick (concentration ≥10 mg/L defined as screen positive for tuberculosis). Sputum samples were collected for Xpert MTB/RIF testing and culture. We calculated the sensitivity and specificity of point-of-care CRP and WHO symptom-based screening in reference to culture results. We repeated the sensitivity analysis with Xpert MTB/RIF as the reference standard.FindingsBetween July 8, 2013, and Dec 15, 2015, 1237 HIV-infected adults were enrolled and underwent point-of-care CRP testing. 60 (5%) patients with incomplete or contaminated cultures were excluded from the analysis. Of the remaining 1177 patients (median CD4 count 165 cells per μL [IQR 75-271]), 163 (14%) had culture-confirmed tuberculosis. Point-of-care CRP testing had 89% sensitivity (145 of 163, 95% CI 83-93) and 72% specificity (731 of 1014, 95% CI 69-75) for culture-confirmed tuberculosis. Compared with WHO symptom-based screening, point-of-care CRP testing had lower sensitivity (difference -7%, 95% CI -12 to -2; p=0·002) but substantially higher specificity (difference 58%, 95% CI 55 to 61; p<0·0001). When Xpert MTB/RIF results were used as the reference standard, sensitivity of point-of-care CRP and WHO symptom-based screening were similar (94% [79 of 84] vs 99% [83 of 84], respectively; difference -5%, 95% CI -12 to 2; p=0·10).InterpretationThe performance characteristics of CRP support its use as a tuberculosis screening test for people living with HIV with CD4 count less than or equal to 350 cells per μL who are initiating ART. HIV/AIDS programmes should consider point-of-care CRP-based tuberculosis screening to improve the efficiency of intensified case finding and increase uptake of tuberculosis preventive therapy.FundingNational Institutes of Health; President's Emergency Plan for AIDS Relief; University of California, San Francisco, Nina Ireland Program for Lung Health.

Project description:BackgroundMost tuberculosis-related deaths in people with HIV could be prevented with earlier diagnosis and treatment. The only commercially available tuberculosis point-of-care test (Alere Determine TB LAM Ag [AlereLAM]) has suboptimal sensitivity, which restricts its use in clinical practice. The novel Fujifilm SILVAMP TB LAM (FujiLAM) assay has been developed to improve the sensitivity of AlereLAM. We assessed the diagnostic accuracy of the FujiLAM assay for the detection of tuberculosis in hospital inpatients with HIV compared with the AlereLAM assay.MethodsFor this diagnostic accuracy study, we assessed biobanked urine samples obtained from the FIND Specimen Bank and the University of Cape Town Biobank, which had been collected from hospital inpatients (aged ≥18 years) with HIV during three independent prospective cohort studies done at two South African hospitals. Urine samples were tested using FujiLAM and AlereLAM assays. The conduct and reporting of each test was done blind to other test results. The primary objective was to assess the diagnostic accuracy of FujiLAM compared with AlereLAM, against microbiological and composite reference standards (including clinical diagnoses).FindingsBetween April 18, 2018, and May 3, 2018, urine samples from 968 hospital inpatients with HIV were evaluated. The prevalence of microbiologically-confirmed tuberculosis was 62% and the median CD4 count was 86 cells per μL. Using the microbiological reference standard, the estimated sensitivity of FujiLAM was 70·4% (95% CI 53·0 to 83·1) compared with 42·3% (31·7 to 51·8) for AlereLAM (difference 28·1%) and the estimated specificity of FujiLAM was 90·8% (86·0 to 94·4) and 95·0% (87·7-98·8) for AlereLAM (difference -4·2%). Against the composite reference standard, the specificity of both assays was higher (95·7% [92·0 to 98·0] for FujiLAM vs 98·2% [95·7 to 99·6] for AlereLAM; difference -2·5%), but the sensitivity of both assays was lower (64·9% [50·1 to 76·7] for FujiLAM vs 38·2% [28·1 to 47·3] for AlereLAM; difference 26·7%).InterpretationIn comparison to AlereLAM, FujiLAM offers superior diagnostic sensitivity, while maintaining specificity, and could transform rapid point-of-care tuberculosis diagnosis for hospital inpatients with HIV. The applicability of FujiLAM for settings of intended use requires prospective assessment.FundingGlobal Health Innovative Technology Fund, UK Department for International Development, Dutch Ministry of Foreign Affairs, Bill & Melinda Gates Foundation, German Federal Ministry of Education and Research, Australian Department of Foreign Affairs and Trade, Wellcome Trust, Department of Science and Technology and National Research Foundation of South Africa, and South African Medical Research Council.

Project description:PurposeThe NCDzz study is a prospective cohort of people living with and without HIV attending primary care clinics in Zambia and Zimbabwe and was established in 2019 to understand the intersection between noncommunicable diseases (NCDs) and HIV in Southern Africa. Here, we describe the study design and population and evaluate their ideal cardiovascular health (ICVH) using the Life's Simple 7 (LS7) score according to the American Heart Association.ParticipantsAntiretroviral therapy-naïve people living with HIV (PLWH) and people living without HIV (PLWOH) 30 years or older were recruited from three primary care clinics in Lusaka and Harare, and underwent comprehensive clinical, laboratory and behavioural assessments. All study measurements are repeated during yearly follow-up visits. PLWOH were recruited from the same neighbourhoods and had similar socioeconomic conditions as PLWH.Findings to dateBetween August 2019 and March 2023, we included 1100 adults, of whom 618 (56%) were females and 539 (49%) were PLWH. The median age at enrolment was 39 years (IQR 34-46 years). Among 1013 participants (92%) with complete data, the median LS7 score was 11/14 (IQR 10-12). Overall, 60% of participants met the criteria of ICVH metrics (5-7 ideal components) and among individual components of the LS7, more females had poor body mass index (BMI) than males, regardless of HIV status (27% vs 3%, p<0.001). Our data show no apparent difference in cardiovascular health determinants between men and women, but high BMI in women and overall high hypertension prevalence need detailed investigation. Untreated HIV (OR: 1.36 (IQR 1.05-1.78)) and being a Zambian participant (OR: 1.81 (IQR 1.31-2.51)) were associated with having ICVH metrics, whereas age older than 50 years (OR: 0.46 (IQR 0.32-0.65)) was associated with not having ICVH metrics.Future plansOur study will be regularly updated with upcoming analyses using prospective data including a focus on arterial hypertension and vascular function. We plan to enrich the work through conducting in-depth assessments on the determinants of cardiovascular, liver and kidney end-organ disease outcomes yearly. Additionally, we seek to pilot NCD interventions using novel methodologies like the trials within cohorts. Beyond the initial funding support, we aim to collect at minimum yearly data for an additional 5-year period.

Project description:IntroductionNovel point-of-care assays which measure urine tenofovir (TFV) concentrations may have a role in improving adherence monitoring for people living with HIV (PLHIV) receiving antiretroviral therapy (ART). However, further studies of their diagnostic accuracy, and whether results are associated with viraemia and drug resistance, are needed to guide their use, particularly in the context of the global dolutegravir rollout.MethodsWe conducted a cross-sectional evaluation among PLHIV receiving first-line ART containing tenofovir disoproxil fumarate at enrolment into a randomized trial in two South African public sector clinics. We calculated the diagnostic accuracy of the Abbott point-of-care immunoassay to detect urine TFV compared to liquid chromatography-tandem mass spectrometry (LC-MS/MS). We evaluated the association between point-of-care urine TFV results and self-reported adherence, viraemia ≥1000 copies/ml and HIV drug resistance, among people receiving either efavirenz or dolutegravir-based ART.ResultsBetween August 2020 and March 2022, we enrolled 124 participants. The median age was 39 (IQR 34-45) years, 55% were women, 74 (59.7%) were receiving efavirenz and 50 (40.3%) dolutegravir. The sensitivity and specificity of the immunoassay to detect urine TFV ≥1500 ng/ml compared to LC-MS/MS were 96.1% (95% CI 90.0-98.8) and 95.2% (75.3-100.0), respectively. Urine TFV results were associated with short (p<0.001) and medium-term (p = 0.036) self-reported adherence. Overall, 44/124 (35.5%) had viraemia, which was associated with undetectable TFV in those receiving efavirenz (OR 6.01, 1.27-39.0, p = 0.014) and dolutegravir (OR 25.7, 4.20-294.8, p<0.001). However, in those with viraemia while receiving efavirenz, 8/27 (29.6%) had undetectable urine TFV, compared to 11/17 (64.7%) of those receiving dolutegravir. Drug resistance was detected in 23/27 (85.2%) of those receiving efavirenz and only 1/16 (6.3%) of those receiving dolutegravir. There was no association between urine TFV results and drug resistance.ConclusionsAmong PLHIV receiving ART, a rapid urine TFV immunoassay can be used to accurately monitor urine TFV levels compared to the gold standard of LC-MS/MS. Undetectable point-of-care urine TFV results were associated with viraemia, particularly among people receiving dolutegravir.Trial registrationPan-African Clinical Trials Registry: PACTR202001785886049.

Project description:ObjectiveThe burden of non-communicable diseases (NCDs) is increasing among populations living in humanitarian settings. Continuity of care (CoC) involves following an individual over time and across different levels of healthcare (management, longitudinal, informational and interpersonal continuity); it is an essential component of good quality, person-centred NCD care. Providing CoC is particularly challenging in humanitarian crises where health care access may be interrupted or restricted. This paper aimed to explore health actors' experiences of continuity of hypertension and diabetes care for Syrian refugees and vulnerable Lebanese in Lebanon.MethodsWe conducted 20 in-depth qualitative interviews with health actors, including eleven with health care providers at four urban-based health facilities supported by international humanitarian agencies that provide NCD care to Syrian refugees and vulnerable Lebanese, one representative of a governmental institution, one international delegate and seven humanitarian actors. Thematic analysis, combining inductive and deductive approaches, was guided by a conceptual framework for NCD models of care in humanitarian settings. We reported our findings against the conceptual framework's domains relating to health system inputs and intermediate goals, reflecting on their impact on the domains of CoC.FindingsExisting health system weaknesses and novel challenges (the economic crisis, COVID-19 pandemic and Beirut blast) to continuity of NCD care were identified. Health system input challenges: governance and financing (weakened governance, limited central financing, historical dependence on local NGOs for primary healthcare, a dominant private sector), health workforce (exodus of health care providers from the public system), inconsistent medicines and equipment supplies, and limited health information systems (no unified system across institutions or levels of care, lack of formal referral systems, and inconsistent facility-level data collection) contributed to limited public primary care, poorly integrated within a fragile, pluralistic health system. These factors negatively impacted the intermediate health system goals of access, standardisation and quality of NCD care for Syrian refugee and Lebanese patients, and collectively hampered the management, longitudinal, informational and interpersonal continuity of NCD care in Lebanon.ConclusionWe recommend that humanitarian actors continue the work underway with the Lebanese Ministry of Public Health to align with and strengthen health system inputs, including supporting health governance through the accreditation process, exploring new funding mechanisms, strengthening the workforce via task sharing and training, supporting the medication supply chain, improving access to facilities and service quality, and supporting the development, standardisation and interoperability of referral and information systems. In combination, these elements will support better CoC for people living with hypertension and diabetes in Lebanon.

Dataset Information

Diagnostic Accuracy of the Alere Afinion AS100 Point-of-Care Assay to Screen for Noncommunicable Diseases Among People Living With HIV.

Publications

Diagnostic Accuracy of the Alere Afinion AS100 Point-of-Care Assay to Screen for Noncommunicable Diseases Among People Living With HIV.

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