CROI 2024: Tuberculosis, Mpox, and Other Infectious Complications in People With HIV.

Several novel antituberculosis agents, including long-acting injectable agents in mouse models, have shown promise in preclinical and early clinical studies. This encouraging news is offset by the failures of a tuberculosis (TB) vaccine to prevent disease recurrence and a 3-month clofazimine-based treatment regimen for drug-susceptible TB. Clinically focused insights regarding TB, mpox, and other HIV-associated infectious complications that were presented at the 2024 Conference on Retroviruses and Opportunistic Infections (CROI) are summarized in this review.

Mapping the existing body of knowledge on new and repurposed TB vaccine implementation: A scoping review.

There is global consensus on the urgent need for a safe and effective TB vaccine for adults and adolescents to improve global TB control, and encouragingly, several promising candidates have advanced to late-stage trials. Significant gaps remain in understanding the critical factors that will facilitate the successful implementation of new and repurposed TB vaccines in low- and middle-income countries (LMICs), once available. By synthesizing the existing body of knowledge, this review offers comprehensive insights into the current state of research on implementation of these adult and adolescent vaccines. This review explores four key dimensions: (1) epidemiological impact, (2) costing, cost-effectiveness, and/or economic impact, (3) acceptability, and the (4) feasibility of implementation; this includes implementation strategies of target populations, and health system capabilities. Results indicate that current research primarily consists of epidemiological and costing/cost-effectiveness/economic studies in India, China, and South Africa, mainly modelling with M72/AS01, BCG revaccination, and hypothetical vaccines. Varying endpoints, vaccine efficacies, and vaccination coverages were used. Globally, new, and repurposed TB vaccines are estimated to save millions of lives. Economically, these vaccines also demonstrate promise with expected cost-effectiveness in most countries. Projected outcomes were dependent on vaccine characteristics, target population, implementation strategy, timing of roll out, TB burden/country context, and vaccination coverage. Potential barriers for vaccine acceptability included TB-related stigma, need for a second dose, and cost, while low pricing, community and civil society engagement and heightened public TB awareness were potential enablers in China, India, and South Africa. Potential implementation strategies considered spanned from mass campaigns to integration within existing vaccine programs and the primary target group studied was the general population, and adults and adolescents. In conclusion, future research must have broader geographical representations to better understand what is needed to inform tailored vaccine programs to accommodate diverse country contexts and population groups to achieve optimal implementation and impact. Furthermore, this review underscores the scarcity of research on acceptability of new and repurposed TB vaccines and their delivery among potential beneficiaries, the most promising implementation strategies, and the health system capabilities necessary for implementation. The absence of this knowledge in these areas emphasizes the crucial need for future research to ensure effective TB vaccine implementation in high burden settings worldwide.

A prospective evaluation of the diagnostic accuracy of the point-of-care VISITECT CD4 Advanced Disease test in seven countries.

BACKGROUND: CD4 measurement is pivotal in the management of advanced HIV disease. VISITECT® CD4 Advanced Disease (AccuBio Limited, Alva, UK; VISITECT) is an instrument-free, point-of-care, semi-quantitative test allowing visual identification of a CD4 ≤200 cells/µl, or >200 cells/µl from finger-prick or venous blood. METHODS: As part of a diagnostic accuracy study of FUJIFILM SILVAMP TB LAM (clinicaltrials.gov: NCT04089423), people living with HIV of ≥18 years old were prospectively recruited in seven countries from outpatient departments if a tuberculosis symptom was present, and from inpatient departments. Participants provided venous blood for CD4 measurement using flow cytometry (reference standard) and finger-prick blood for VISITECT (index text), performed at point-of-care. Sensitivity, specificity, and positive and negative predictive values of VISITECT to determine a CD4 ≤200 cells/µl were evaluated. RESULTS: Among 1604 participants, the median flow cytometry CD4 was 367 (IQR 128-626) cells/µl and 521 (32.5%) had a CD4 ≤200 cells/µl. VISITECT sensitivity was 92.7% (483/521, 95% CI 90.1-94.7%) and specificity was 61.4% (665/1083, 95% CI 58.4-64.3%). For participants with a CD4 between 0-100, 101-200, 201-300, 301-500, and >500 cells/µl, VISITECT misclassified 4.5% (95% CI 2.5-7.2%), 12.5 (95% CI 8.0-18.2%), 74.1% (95% CI 67.0-80.5%), 48.0% (95% CI 42.5-53.6%), and 22.6% (95% CI 19.3-26.3%), respectively. CONCLUSIONS: VISITECT's sensitivity, but not specificity, met the World Health Organization's minimal sensitivity and specificity threshold of 80% for point-of-care CD4 tests. VISITECT's quality needs to be assessed and its accuracy optimized. VISITECT´s utility as CD4 triage test should be investigated.

Lessons from a decade of adult vaccine rollout in low- and middle-income countries: a scoping review.

INTRODUCTION: The historical focus of vaccines on child health coupled with the advent of novel vaccines targeting adult populations necessitates exploring strategies for adult vaccine implementation. AREAS COVERED: This scoping review extracts insights from the past decade's experiences introducing adult vaccines in low- and middle-income countries. Among 25 papers reviewed, 19 focused on oral cholera vaccine, 2 on Meningococcal A vaccines, 2 on tetanus toxoid vaccine, 1 on typhoid vaccine, and 1 on Ebola vaccine. Aligned with WHO's Global Framework for New TB Vaccines for Adults and Adolescents, our findings center on vaccine availability, accessibility, and acceptance. EXPERT OPINION: Availability findings underscore the importance of understanding disease burden for prioritization, multi-sectoral collaboration during planning, and strategic resource allocation and coordination. Accessibility results highlight the benefits of leveraging existing health infrastructure and adequately training healthcare workers, and contextually tailoring vaccine delivery approaches to reach challenging sub-groups like working male adults. Central to fostering acceptance, resonant sensitization, and communication campaigns engaging the communities and utilizing trusted local leaders countered rumors and increased awareness and uptake. As we approach the introduction of a new adult TB vaccine, insights from this review equips decision-makers with key evidence-based recommendations to support successful and equitable vaccinations targeting adults.

Diagnostic yield as an important metric for the evaluation of novel tuberculosis tests: rationale and guidance for future research.

Better access to tuberculosis testing is a key priority for fighting tuberculosis, the leading cause of infectious disease deaths in people. Despite the roll-out of molecular WHO-recommended rapid diagnostics to replace sputum smear microscopy over the past decade, a large diagnostic gap remains. Of the estimated 10·6 million people who developed tuberculosis globally in 2022, more than 3·1 million were not diagnosed. An exclusive focus on improving tuberculosis test accuracy alone will not be sufficient to close the diagnostic gap for tuberculosis. Diagnostic yield, which we define as the proportion of people in whom a diagnostic test identifies tuberculosis among all people we attempt to test for tuberculosis, is an important metric not adequately explored. Diagnostic yield is particularly relevant for subpopulations unable to produce sputum such as young children, people living with HIV, and people with subclinical tuberculosis. As more accessible non-sputum specimens (eg, urine, oral swabs, saliva, capillary blood, and breath) are being explored for point-of-care tuberculosis testing, the concept of yield will be of growing importance. Using the example of urine lipoarabinomannan testing, we illustrate how even tests with limited sensitivity can diagnose more people with tuberculosis if they enable increased diagnostic yield. Using tongue swab-based molecular tuberculosis testing as another example, we provide definitions and guidance for the design and conduct of pragmatic studies that assess diagnostic yield. Lastly, we show how diagnostic yield and other important test characteristics, such as cost and implementation feasibility, are essential for increased effective population coverage, which is required for optimal clinical care and transmission impact. We are calling for diagnostic yield to be incorporated into tuberculosis test evaluation processes, including the WHO Grading of Recommendations, Assessment, Development, and Evaluations process, providing a crucial real-life implementation metric that complements traditional accuracy measures.

Prospective multicentre accuracy evaluation of the FUJIFILM SILVAMP TB LAM test for the diagnosis of tuberculosis in people living with HIV demonstrates lot-to-lot variability.

There is an urgent need for rapid, non-sputum point-of-care diagnostics to detect tuberculosis. This prospective trial in seven high tuberculosis burden countries evaluated the diagnostic accuracy of the point-of-care urine-based lipoarabinomannan assay FUJIFILM SILVAMP TB LAM (FujiLAM) among inpatients and outpatients living with HIV. Diagnostic performance of FujiLAM was assessed against a mycobacterial reference standard (sputum culture, blood culture, and Xpert Ultra from urine and sputum at enrollment, and additional sputum culture ≤7 days from enrollment), an extended mycobacterial reference standard (eMRS), and a composite reference standard including clinical evaluation. Of 1637 participants considered for the analysis, 296 (18%) were tuberculosis positive by eMRS. Median age was 40 years, median CD4 cell count was 369 cells/ul, and 52% were female. Overall FujiLAM sensitivity was 54·4% (95% CI: 48·7-60·0), overall specificity was 85·2% (83·2-87·0) against eMRS. Sensitivity and specificity estimates varied between sites, ranging from 26·5% (95% CI: 17·4%-38·0%) to 73·2% (60·4%-83·0%), and 75·0 (65·0%-82·9%) to 96·5 (92·1%-98·5%), respectively. Post-hoc exploratory analysis identified significant variability in the performance of the six FujiLAM lots used in this study. Lot variability limited interpretation of FujiLAM test performance. Although results with the current version of FujiLAM are too variable for clinical decision-making, the lipoarabinomannan biomarker still holds promise for tuberculosis diagnostics. The trial is registered at clinicaltrials.gov (NCT04089423).

CROI 2023: Tuberculosis and Infectious Complications in Persons With HIV.

Novel implementation strategies to increase uptake and adherence to tuberculosis (TB) preventive therapy hold promise for reducing TB incidence in persons with HIV in high-burden settings. In persons who develop drug-susceptible TB, progress to shorten TB treatment continues to be made with the introduction of new drugs and novel treatment strategies that could allow for treatment shortening to 2 months for most people. A global case series provided powerful evidence that mpox should be considered an HIV-related opportunistic infection given its severe manifestations and poor outcomes. Studies of TB and infectious complications in people with HIV presented at the 2023 Conference on Retroviruses and Opportunistic Infections (CROI) are summarized herein.

Preferences of people living with HIV for features of tuberculosis preventive treatment regimens - a discrete choice experiment.

Background: Tuberculosis (TB) preventive treatment (TPT) is recommended for people living with HIV (PLHIV) in high TB burden settings. While 6 months of daily isoniazid remains widely used, shorter regimens are now available. However, little is known about preferences of PLHIV for key features of TPT regimens. Methods: We conducted a discrete choice experiment among adult PLHIV engaged in care at an urban HIV clinic in Kampala, Uganda. In nine random choice tasks, participants chose between two hypothetical TPT regimens with different features (pills per dose, frequency, duration, need for adjusted antiretroviral therapy [ART] dosage and side effects). We analyzed preferences using hierarchical Bayesian estimation, latent class analysis, and willingness-to-trade simulations. Results: Of 400 PLHIV, 392 (median age 44, 72% female, 91% TPT-experienced) had high quality choice task responses. Pills per dose was the most important attribute (relative importance 32.4%, 95% confidence interval [CI] 31.6 - 33.2), followed by frequency (20.5% [95% CI 19.7 - 21.3]), duration (19.5% [95% CI 18.6 - 20.5]), and need for ART dosage adjustment (18.2% [95% CI 17.2 - 19.2]). Latent class analysis identified three preference groups: one prioritized less frequent, weekly dosing (N=222; 57%); another was averse to ART dosage adjustment (N=107; 27%); and the last prioritized short and tolerable regimens (N=63; 16%). All groups highly valued fewer pills per dose. Participants were willing to accept a regimen of 2.8 months' additional duration [95% CI: 2.4 - 3.2] to reduce pills per dose from five to one, 3.6 [95% CI 2.4 - 4.8] months for weekly rather than daily dosing, and 2.2 [95% CI 1.3 - 3.0] months to avoid ART dosage adjustment. Conclusions: To align with preferences of PLHIV, decision-makers should prioritize the development and implementation of TPT regimens with fewer pills, less frequent dosing, and no need for ART dosage adjustment, rather than focus primarily on duration of treatment.

Improving measurement of tuberculosis care cascades to enhance people-centred care.

Care cascades represent the proportion of people reaching milestones in care for a disease and are widely used to track progress towards global targets for HIV and other diseases. Despite recent progress in estimating care cascades for tuberculosis (TB) disease, they have not been routinely applied at national and subnational levels, representing a lost opportunity for public health impact. As researchers who have estimated TB care cascades in high-incidence countries (India, Madagascar, Nigeria, Peru, South Africa, and Zambia), we describe the utility of care cascades and identify measurement challenges, including the lack of population-based disease burden data and electronic data capture, the under-reporting of people with TB navigating fragmented and privatised health systems, the heterogeneity of TB tests, and the lack of post-treatment follow-up. We outline an agenda for rectifying these gaps and argue that improving care cascade measurement is crucial to enhancing people-centred care and achieving the End TB goals.

Strategies to increase childhood tuberculosis case detection at the primary health care level: Lessons from an active case finding study in Zambia.

INTRODUCTION: In high TB burden settings, it is estimated that 10-20% of total notifications should be children, however, currently only 6-8% of the total TB notifications in Zambia are children. We assessed whether the implementation of a multicomponent strategy, at primary healthcare facilities, that systematically targets barriers at each step of the childhood TB diagnostic cascade can increase childhood TB case detection. METHODS: We conducted a controlled, interrupted time series analysis to compare childhood TB case notifications before (January 2018-December 2019), and during implementation (January 2020-September 2021) in two intervention and two control Level 1 hospitals in Lusaka, Zambia. At each of the intervention facilities, we implemented a multicomponent strategy constituting: (1) capacity development on childhood TB and interpretation of chest x-ray, (2) TB awareness-raising and demand creation activities, (3) setting up fast track TB services, (4) strengthening of household contact tracing, and (5) improving access to digital chest X-ray for TB screening and Xpert MTB/Rif Ultra for TB diagnosis, through strengthening sample collection in children. FINDINGS: Among 5,150 children < 15 years screened at the two intervention facilities during the study period, 503 (9.8% yield) were diagnosed with TB. Of these, 433 (86.1%) were identified through facility-based activities (10.5% yield) and 70 (13.9%) were identified through household contact tracing (6.9% yield). Overall, 446 children (88.7%) children with TB were clinically diagnosed. Following implementation of the multicomponent strategy, the proportion children contributed to total TB notifications immediately changed by +1.5% (95%CI: -3.5, 6.6) and -4.4% (95%CI: -7.5, 1.4) at the intervention and control sites, respectively (difference 6.0% [95%CI: -0.7, 12.7]), p = 0.08); the proportion of childhood notifications increased 0.9% (95%CI: -0.7, 2.5%) each quarter at the intervention sites relative to pre-implementation trends, while declining 1.2% (-95%CI: -1.8, -0.6) at the control sites (difference 2.1% [95%CI: 0.1, 4.2] per quarter between, p = 0.046); this translated into 352 additional and 85 fewer childhood TB notifications at the intervention and control sites, respectively, compared to the pre-implementation period. CONCLUSION: A standardized package of strategies to improve childhood TB detection at primary healthcare facilities was feasible to implement and was associated with a sustained improvement in childhood TB notifications.

Clinical utility of WHO-recommended screening tools and development and validation of novel clinical prediction models for pulmonary tuberculosis screening among outpatients living with HIV: an individual participant data meta-analysis.

BACKGROUND: The World Health Organization (WHO) recommends that outpatient people living with HIV (PLHIV) undergo tuberculosis screening with the WHO four-symptom screen (W4SS) or C-reactive protein (CRP) (5 mg·L-1 cut-off) followed by confirmatory testing if screen positive. We conducted an individual participant data meta-analysis to determine the performance of WHO-recommended screening tools and two newly developed clinical prediction models (CPMs). METHODS: Following a systematic review, we identified studies that recruited adult outpatient PLHIV irrespective of tuberculosis signs and symptoms or with a positive W4SS, evaluated CRP and collected sputum for culture. We used logistic regression to develop an extended CPM (which included CRP and other predictors) and a CRP-only CPM. We used internal-external cross-validation to evaluate performance. RESULTS: We pooled data from eight cohorts (n=4315 participants). The extended CPM had excellent discrimination (C-statistic 0.81); the CRP-only CPM had similar discrimination. The C-statistics for WHO-recommended tools were lower. Both CPMs had equivalent or higher net benefit compared with the WHO-recommended tools. Compared with both CPMs, CRP (5 mg·L-1 cut-off) had equivalent net benefit across a clinically useful range of threshold probabilities, while the W4SS had a lower net benefit. The W4SS would capture 91% of tuberculosis cases and require confirmatory testing for 78% of participants. CRP (5 mg·L-1 cut-off), the extended CPM (4.2% threshold) and the CRP-only CPM (3.6% threshold) would capture similar percentages of cases but reduce confirmatory tests required by 24, 27 and 36%, respectively. CONCLUSIONS: CRP sets the standard for tuberculosis screening among outpatient PLHIV. The choice between using CRP at 5 mg·L-1 cut-off or in a CPM depends on available resources.

A mixed methods study on men's and women's tuberculosis care journeys in Lusaka, Zambia-Implications for gender-tailored tuberculosis health promotion and case finding strategies.

Men and women with undiagnosed tuberculosis (TB) in high burden countries may have differential factors influencing their healthcare seeking behaviors and access to TB services, which can result in delayed diagnoses and increase TB-related morbidity and mortality. A convergent, parallel, mixed-methods study design was used to explore and evaluate TB care engagement among adults (≥18 years) with newly diagnosed, microbiologically-confirmed TB attending three public health facilities in Lusaka, Zambia. Quantitative structured surveys characterized the TB care pathway (time to initial care-seeking, diagnosis, and treatment initiation) and collected information on factors influencing care engagement. Multinomial multivariable logistic regression was used to determine predicted probabilities of TB health-seeking behaviors and determinants of care engagement. Qualitative in-depth interviews (IDIs; n = 20) were conducted and analyzed using a hybrid approach to identify barriers and facilitators to TB care engagement by gender. Overall, 400 TB patients completed a structured survey, of which 275 (68.8%) and 125 (31.3%) were men and women, respectively. Men were more likely to be unmarried (39.3% and 27.2%), have a higher median daily income (50 and 30 Zambian Kwacha [ZMW]), alcohol use disorder (70.9% [AUDIT-C score ≥4] and 31.2% [AUDIT-C score ≥3]), and a history of smoking (63.3% and 8.8%), while women were more likely to be religious (96.8% and 70.8%) and living with HIV (70.4% and 36.0%). After adjusting for potential confounders, the probability of delayed health-seeking ≥4 weeks after symptom onset did not differ significantly by gender (44.0% and 36.2%, p = 0.14). While the top reasons for delayed healthcare-seeking were largely similar by gender, men were more likely to report initially perceiving their symptoms as not being serious (94.8% and 78.7%, p = 0.032), while women were more likely to report not knowing the symptoms of TB before their diagnosis (89.5% and 74.4%; p = 0.007) and having a prior bad healthcare experience (26.4% and 9.9%; p = 0.036). Notably, women had a higher probability of receiving TB diagnosis ≥2 weeks after initial healthcare seeking (56.5% and 41.0%, p = 0.007). While men and women reported similar acceptability of health-information sources, they emphasized different trusted messengers. Also, men had a higher adjusted probability of stating that no one influenced their health-related decision making (37.9% and 28.3%, p = 0.001). In IDIs, men recommended TB testing sites at convenient community locations, while women endorsed an incentivized, peer-based, case-finding approach. Sensitization and TB testing strategies at bars and churches were highlighted as promising approaches to reach men and women, respectively. This mixed-methods study found important differences between men and women with TB in Zambia. These differences suggest the need for gender-tailored TB health promotion, including addressing harmful alcohol use and smoking among men, and sensitizing HCWs to prolonged delays in TB diagnosis among women, and also using gender-specific approaches as part of community-based, active case-finding strategies to improve TB diagnosis in high burden settings.

Correction: Evaluation of kidney function among people living with HIV initiating antiretroviral therapy in Zambia.

[This corrects the article DOI: 10.1371/journal.pgph.0000124.].

Diagnostic yield of urine lipoarabinomannan and sputum tuberculosis tests in people living with HIV: a systematic review and meta-analysis of individual participant data.

BACKGROUND: Sputum is the most widely used sample to diagnose active tuberculosis, but many people living with HIV are unable to produce sputum. Urine, in contrast, is readily available. We hypothesised that sample availability influences the diagnostic yield of various tuberculosis tests. METHODS: In this systematic review and meta-analysis of individual participant data, we compared the diagnostic yield of point-of-care urine-based lipoarabinomannan tests with that of sputum-based nucleic acid amplification tests (NAATs) and sputum smear microscopy (SSM). We used microbiologically confirmed tuberculosis based on positive culture or NAAT from any body site as the denominator and accounted for sample provision. We searched PubMed, Web of Science, Embase, African Journals Online, and clinicaltrials.gov from database inception to Feb 24, 2022 for randomised controlled trials, cross-sectional studies, and cohort studies that assessed urine lipoarabinomannan point-of-care tests and sputum NAATs for active tuberculosis detection in participants irrespective of tuberculosis symptoms, HIV status, CD4 cell count, or study setting. We excluded studies in which recruitment was not consecutive, systematic, or random; provision of sputum or urine was an inclusion criterion; less than 30 participants were diagnosed with tuberculosis; early research assays without clearly defined cutoffs were tested; and humans were not studied. We extracted study-level data, and authors of eligible studies were invited to contribute deidentified individual participant data. The main outcomes were the tuberculosis diagnostic yields of urine lipoarabinomannan tests, sputum NAATs, and SSM. Diagnostic yields were predicted using Bayesian random-effects and mixed-effects meta-analyses. This study is registered with PROSPERO, CRD42021230337. FINDINGS: We identified 844 records, from which 20 datasets and 10 202 participants (4561 [45%] male participants and 5641 [55%] female participants) were included in the meta-analysis. All studies assessed sputum Xpert (MTB/RIF or Ultra, Cepheid, Sunnyvale, CA, USA) and urine Alere Determine TB LAM (AlereLAM, Abbott, Chicago, IL, USA) in people living with HIV aged 15 years or older. Nearly all (9957 [98%] of 10 202) participants provided urine, and 82% (8360 of 10 202) provided sputum within 2 days. In studies that enrolled unselected inpatients irrespective of tuberculosis symptoms, only 54% (1084 of 1993) of participants provided sputum, whereas 99% (1966 of 1993) provided urine. Diagnostic yield was 41% (95% credible interval [CrI] 15-66) for AlereLAM, 61% (95% Crl 25-88) for Xpert, and 32% (95% Crl 10-55) for SSM. Heterogeneity existed across studies in the diagnostic yield, influenced by CD4 cell count, tuberculosis symptoms, and clinical setting. In predefined subgroup analyses, all tests had higher yields in symptomatic participants, and AlereLAM yield was higher in those with low CD4 counts and inpatients. AlereLAM and Xpert yields were similar among inpatients in studies enrolling unselected participants who were not assessed for tuberculosis symptoms (51% vs 47%). AlereLAM and Xpert together had a yield of 71% in unselected inpatients, supporting the implementation of combined testing strategies. INTERPRETATION: AlereLAM, with its rapid turnaround time and simplicity, should be prioritised to inform tuberculosis therapy among inpatients who are HIV-positive, regardless of symptoms or CD4 cell count. The yield of sputum-based tuberculosis tests is undermined by people living with HIV who cannot produce sputum, whereas nearly all participants are able to provide urine. The strengths of this meta-analysis are its large size, the carefully harmonised denominator, and the use of Bayesian random-effects and mixed-effects models to predict yields; however, data were geographically restricted, clinically diagnosed tuberculosis was not considered in the denominator, and little information exists on strategies for obtaining sputum samples. FUNDING: FIND, the Global Alliance for Diagnostics.

The Performance of Computer-Aided Detection Digital Chest X-ray Reading Technologies for Triage of Active Tuberculosis Among Persons With a History of Previous Tuberculosis.

BACKGROUND: Digital chest X-ray (dCXR) computer-aided detection (CAD) technology uses lung shape and texture analysis to determine the probability of tuberculosis (TB). However, many patients with previously treated TB have sequelae, which also distort lung shape and texture. We evaluated the diagnostic performance of 2 CAD systems for triage of active TB in patients with previously treated TB. METHODS: We conducted a retrospective analysis of data from a cross-sectional active TB case finding study. Participants ≥15 years, with ≥1 current TB symptom and complete data on history of previous TB, dCXR, and TB microbiological reference (Xpert MTB/RIF) were included. dCXRs were evaluated using CAD4TB (v.7.0) and qXR (v.3.0). We determined the diagnostic accuracy of both systems, overall and stratified by history of TB, using a single threshold for each system that achieved 90% sensitivity and maximized specificity in the overall population. RESULTS: Of 1884 participants, 452 (24.0%) had a history of previous TB. Prevalence of microbiologically confirmed TB among those with and without history of previous TB was 12.4% and 16.9%, respectively. Using CAD4TB, sensitivity and specificity were 89.3% (95% CI: 78.1-96.0%) and 24.0% (19.9-28.5%) and 90.5% (86.1-93.3%) and 60.3% (57.4-63.0%) among those with and without previous TB, respectively. Using qXR, sensitivity and specificity were 94.6% (95% CI: 85.1-98.9%) and 22.2% (18.2-26.6%) and 89.7% (85.1-93.2%) and 61.8% (58.9-64.5%) among those with and without previous TB, respectively. CONCLUSIONS: The performance of CAD systems as a TB triage tool is decreased among persons previously treated for TB.

A world of choices: preference elicitation methods for improving the delivery and uptake of HIV prevention and treatment.

PURPOSE OF REVIEW: Despite the growing availability of effective HIV prevention and treatment interventions, there are large gaps in their uptake and sustained use across settings. It is crucial to elicit and apply patients' and stakeholders' preferences to maximize the impact of existing and future interventions. This review summarizes quantitative preference elicitation methods (PEM) and how they can be applied to improve the delivery and uptake of HIV prevention and treatment interventions. RECENT FINDINGS: PEM are increasingly applied in HIV implementation research; however, discrete choice experiments (DCEs) have predominated. Beyond DCEs, there are other underutilized PEM that may improve the reach and effectiveness of HIV prevention and treatment interventions among individuals by prioritizing their barriers to engagement and determining which attributes of interventions and delivery strategies are most valued. PEM can also enhance the adoption and sustained implementation of strategies to deliver HIV prevention and treatment interventions by assessing which attributes are the most acceptable and appropriate to key stakeholders. SUMMARY: Greater attention to and incorporation of patient's and stakeholders' preferences for HIV prevention and treatment interventions and their delivery has the potential to increase the number of persons accessing and retained in HIV prevention and treatment services.

Placing the values and preferences of people most affected by TB at the center of screening and testing: an approach for reaching the unreached.

To reach the millions of people with tuberculosis (TB) undiagnosed each year, there is an important need to provide people-centered screening and testing services. Despite people-centered care being a key pillar of the WHO END-TB Strategy, there have been few attempts to formally characterize and integrate the preferences of people most affected by TB - including those who have increased exposure to TB, limited access to services, and/or are at increased risk for TB - into new tools and strategies to improve screening and diagnosis. This perspective emphasizes the importance of preference research among people most affected by TB, provides an overview of qualitative preference exploration and quantitative preference elicitation research methods, and outlines how preferences can be applied to improve the acceptability, accessibility, and appropriateness of TB screening and testing services via four key opportunities. These include the following: (1) Defining the most preferred features of novel screening, triage, and diagnostic tools, (2) exploring and prioritizing setting-specific barriers and facilitators to screening and testing, (3) understanding what features of community- and facility-based strategies for improving TB detection and treatment are most valued, and (4) identifying the most relevant and resonant communication strategies to increase individual- and community-level awareness and demand. Preference research studies and translation of their findings into policy/guidance and operationalization have enormous potential to close the existing gaps in detection in high burden settings by enhancing the people-centeredness and reach of screening and diagnostic services to people most affected by TB who are currently being missed and left behind.

CROI 2022: tuberculosis and infectious complications in persons With HIV.

Early treatment of anal high-grade squamous intraepithelial lesions compared with active monitoring reduced the risk of anal cancer by 57% in persons with HIV in a landmark randomized trial of 4446 participants. In a multi- country randomized trial, an entirely oral combination regimen consisting of bedaquiline, pretomanid, linezolid, and moxifloxacin for 24 weeks outperformed the World Health Organization-recommended 36- to 96-week standard of care regimen for multidrug-resistant tuberculosis (TB), ushering in a new era of shorter multidrug-resistant TB treatment. These and other studies of TB and coinfections in persons with HIV presented at the 2022 Conference on Retroviruses and Opportunistic Infections pro vided new insights and are summarized herein.

COVID-19 Symptoms and Duration of Rapid Antigen Test Positivity at a Community Testing and Surveillance Site During Pre-Delta, Delta, and Omicron BA.1 Periods.

Importance: Characterizing the clinical symptoms and evolution of community-based SARS-CoV-2 infections may inform health practitioners and public health officials in a rapidly changing landscape of population immunity and viral variants. Objectives: To compare COVID-19 symptoms among people testing positive with a rapid antigen test (RAT) during the Omicron BA.1 variant period (December 1, 2021, to January 30, 2022) with the pre-Delta (January 10 to May 31, 2021) and Delta (June 1 to November 30, 2021) variant periods and to assess the duration of RAT positivity during the Omicron BA.1 surge. Design, Setting, and Participants: This cross-sectional study was conducted from January 10, 2021, to January 31, 2022, at a walk-up community COVID-19 testing site in San Francisco, California. Participants included children and adults seeking COVID-19 testing with an RAT, regardless of age, vaccine status, or symptoms. Main Outcomes and Measures: Fisher exact tests or χ2 tests were used to compare COVID-19 symptoms during the Omicron BA.1 period with the pre-Delta and Delta periods for vaccination status and age group. Among people returning for repeated testing during the Omicron period, the proportion with a positive RAT between 4 and 14 days from symptom onset or since first positive test if asymptomatic was estimated. Results: Among 63 277 persons tested (median [IQR] age, 32 [21-44] years, with 12.0% younger than 12 years; 52.0% women; and 68.5% Latinx), a total of 18 301 people (28.9%) reported symptoms, of whom 4565 (24.9%) tested positive for COVID-19. During the Omicron BA.1 period, 3032 of 7283 symptomatic participants (41.6%) tested positive, and the numbers of these reporting cough and sore throat were higher than during pre-Delta and Delta periods (cough: 2044 [67.4%] vs 546 [51.3%] of 1065 participants, P < .001 for pre-Delta, and 281 [60.0%] of 468 participants, P = .002, for Delta; sore throat: 1316 [43.4%] vs 315 [29.6%] of 1065 participants, P < .001 for pre-Delta, and 136 [29.1%] of 468 participants, P < .001, for Delta). Compared with the 1065 patients with positive test results in the pre-Delta period, congestion among the 3032 with positive results during the Omicron BA.1 period was more common (1177 [38.8%] vs 294 [27.6%] participants, P < .001), and loss of taste or smell (160 [5.3%] vs 183 [17.2%] participants, P < .001) and fever (921 [30.4%] vs 369 [34.7%] participants, P = .01) were less common. In addition, during the Omicron BA.1 period, fever was less common among the people with positive test results who had received a vaccine booster compared with those with positive test results who were unvaccinated (97 [22.5%] of 432 vs 42 [36.2%] of 116 participants, P = .003), and fever and myalgia were less common among participants who had received a booster compared with those with positive results who had received only a primary series (fever: 97 [22.5%] of 432 vs 559 [32.8%] of 1705 participants, P < .001; myalgia: 115 [26.6%] of 432 vs 580 [34.0%] of 1705 participants, P = .003). During the Omicron BA.1 period, 5 days after symptom onset, 507 of 1613 people (31.1%) with COVID-19 stated that their symptoms were similar, and 95 people (5.9%) reported worsening symptoms. Among people testing positive, 80.2% of participants who were symptomatic and retested remained positive 5 days after symptom onset. Conclusions and Relevance: In this cross-sectional study, COVID-19 upper respiratory tract symptoms were more commonly reported during the Omicron BA.1 period than during the pre-Delta and Delta periods, with differences by vaccination status. Rapid antigen test positivity remained high 5 days after symptom onset, supporting guidelines requiring a negative test to inform the length of the isolation period.

Patient Preferences for Strategies to Improve Tuberculosis Diagnostic Services in Zambia.

Importance: Delayed engagement in tuberculosis (TB) services is associated with ongoing transmission and poor clinical outcomes. Objective: To assess whether patients with TB have differential preferences for strategies to improve the public health reach of TB diagnostic services. Design, Setting, and Participants: A cross-sectional study was undertaken in which a discrete choice experiment (DCE) was administered between September 18, 2019, and January 17, 2020, to 401 adults (>18 years of age) with microbiologically confirmed TB in Lusaka, Zambia. The DCE had 7 attributes with 2 to 3 levels per attribute related to TB service enhancements. Latent class analysis was used to identify segments of participants with unique preferences. Multiscenario simulations were used to estimate shares of preferences for different TB service improvement strategies. Main Outcomes and Measures: The main outcomes were patient preference archetypes and estimated shares of preferences for different strategies to improve TB diagnostic services. Collected data were analyzed between January 3, 2022, to July 2, 2022. Results: Among 326 adults with TB (median [IQR] age, 34 [27-42] years; 217 [66.8%] male; 158 [48.8%] HIV positive), 3 groups with distinct preferences for TB service improvements were identified. Group 1 (192 participants [58.9%]) preferred a facility that offered same-day TB test results, shorter wait times, and financial incentives for testing. Group 2 (83 participants [25.4%]) preferred a facility that provided same-day TB results, had greater privacy, and was closer to home. Group 3 (51 participants [15.6%]) had no strong preferences for service improvements and had negative preferences for receiving telephone-based TB test results. Groups 1 and 2 were more likely to report at least a 4-week delay in seeking health care for their current TB episode compared with group 3 (29 [51.3%] in group 1, 95 [35.8%] in group 2, and 10 [19.6%] in group 3; P < .001). Strategies to improve TB diagnostic services most preferred by all participants were same-day TB test results alone (shares of preference, 69.9%) and combined with a small financial testing incentive (shares of preference, 79.3%), shortened wait times (shares of preference, 76.1%), or greater privacy (shares of preference, 75.0%). However, the most preferred service improvement strategies differed substantially by group. Conclusions and Relevance: In this study, patients with TB had heterogenous preferences for TB diagnostic service improvements associated with differential health care-seeking behavior. Tailored strategies that incorporate features most valued by persons with undiagnosed TB, including same-day results, financial incentives, and greater privacy, may optimize reach by overcoming key barriers to timely TB care engagement.