Dynamic PET Reveals Compartmentalized Brain and Lung Tissue Antibiotic Exposures.

Tuberculosis (TB) remains a leading cause of death, but antibiotic treatments for tuberculous meningitis, the deadliest form of TB, are based on those developed for pulmonary TB and not optimized for brain penetration. Here, we performed first-in-human dynamic 18F-pretomanid positron emission tomography (PET) studies in eight human subjects for three-dimensional, multi-compartmental in situ visualization of antibiotic concentration-time exposures (area under the curve - AUC), demonstrating preferential brain (AUCtissue/plasma 2.25) versus lung (AUCtissue/plasma 0.97) tissue partitioning. Preferential, antibiotic-specific partitioning into brain or lung tissues of antibiotics active against MDR strains were confirmed in experimentally-infected mice and rabbits, using dynamic PET with chemically identical antibiotic radioanalogs, and postmortem mass spectrometry measurements. PET-facilitated pharmacokinetic modeling predicted human dosing necessary to attain therapeutic brain exposures in human subjects. These data were used to design optimized, pretomanid-based regimens which were evaluated at human equipotent dosing in a mouse model of TB meningitis, demonstrating excellent bactericidal activity without an increase in intracerebral inflammation or brain injury. Importantly, several antibiotic regimens demonstrated discordant activities in brain and lung tissues in the same animal, correlating with the compartmentalized tissue exposures of the component antibiotics. These data provide a mechanistic basis for the compartmentalized activities of antibiotic regimens, with important implications for the development of antimicrobial regimens for meningitis and other infections in compartments with unique antibiotic penetration.

Randomized Controlled Trial of Clinical Guidelines Versus Interactive Decision-Support for Improving Medical Trainees' Confidence with Latent Tuberculosis Care.

BACKGROUND: In order to eliminate tuberculosis (TB) in the USA, primary care providers must take on an expanded role in the diagnosis and management of latent tuberculosis infection (LTBI). Clinical practice guidelines and recommendations exist for LTBI management, but there is a need for innovative tools to improve medical students' and residents' knowledge of evidence-based practices for LTBI testing and treatment. OBJECTIVE: To assess the impact of LTBI-ASSIST, a free online decision support aid, as a novel educational tool and mechanism of delivering clinical practice guidelines for medical trainees. DESIGN: A single site, randomized controlled trial of trainees delivered by electronic survey. INTERVENTIONS: Medical students and Internal Medicine residents at the Johns Hopkins University School of Medicine. PARTICIPANTS: Participants were randomized in 1:1 ratio to receive the US clinical practice guidelines and recommendations for Latent TB management (control arm) or the guidelines plus an introduction to LTBI-ASSIST (LTBI-ASSIST arm) as they completed a case-based knowledge assessment and reported confidence with domains of LTBI care. MAIN MEASURES: (1) Proportion of questions answered correctly on a case-based knowledge assessment; (2) change in reported confidence with domains of LTBI care. KEY RESULTS: One hundred and thirty participants completed the knowledge assessment. Those randomized to receive the LTBI-ASSIST Tool performed better on the case-based knowledge assessment with a mean score of 75.9% (95% CI: 70.6-81.1), compared to 57.4% (52.8-62.0) in the group that received the guidelines only (p <0.001). Similarly, the LTBI-ASSIST group reported a higher change in confidence (measured as post-assessment confidence minus pre-assessment confidence), compared to the control group, in six of the seven domains of LTBI care. CONCLUSIONS: LTBI-ASSIST can be an effective supplement to existing guidelines in educating medical trainees and helping providers find evidence-based, guideline-supported answers for questions encountered in clinical practice. TRIAL REGISTRATION: NIH Clinical Trial Registry No. NCT05772065.

A National HIV Provider Survey of Antiretroviral Therapy Preferences for Management of Treatment-Naive and Experienced Individuals With Drug Resistance.

Background: HIV clinical practice guidelines outline broad treatment principles but offer less explicit recommendations by permutations of encountered viral resistance. We hypothesize that there is variability in antiretroviral (ARV) regimen decision making among providers when considering HIV drug resistance (HIVDR). Methods: US HIV providers provided ARV regimen recommendations for case vignettes in a series of electronic surveys encompassing variations of HIVDR. Responses were characterized by drugs and classes selected and anticipated activity based on genotypic susceptibility. Heterogeneity was defined as the proportion of unique ARV regimens from total responses. Results: An overall 119 providers from the United States participated. Among case vignettes with isolated M184V and viremia, 85.9% selected a regimen with 2 nucleoside reverse transcriptase inhibitors (NRTIs) + integrase strand transfer inhibitor (INSTI); 9.9% selected regimens with >3 ARVs. Alternatively, in scenarios of viremia with moderate to high-level NRTI resistance, >50% of providers selected an NRTI-sparing regimen, while a minority recommended 2 NRTIs + INSTI (21/123, 17%). In moderate to high-level INSTI resistance, there was response heterogeneity, with no common unifying approach to management (127 unique regimens/181 responses, 70% heterogeneity). Providers used cabotegravir/rilpivirine for treatment simplification in suppressed cases, despite a history of treatment failure (37/205, 36%). Conclusions: Our national survey of US HIV providers revealed a consensus to management of HIV resistance with potential alternative options in cases with low heterogeneity. Providers selected cabotegravir/rilpivirine as a viable treatment simplification strategy in suppressed cases with a history of treatment failure. The responses to the case vignettes could be used an education tool for ARV decision making in HIVDR.

Tuberculosis treatment adherence in the era of COVID-19.

BACKGROUND: In-person directly observed therapy (DOT) is commonly used for tuberculosis (TB) treatment monitoring in the US, with increasing usage of video-DOT (vDOT). We evaluated the impact of COVID-19 on TB treatment adherence, and utilization and effectiveness of vDOT. METHODS: We abstracted routinely collected data on individuals treated for TB disease in Baltimore, Maryland between April 2019 and April 2021. Our primary outcomes were to assess vDOT utilization and treatment adherence, defined as the proportion of prescribed doses (7 days/week) verified by observation (in-person versus video-DOT), comparing individuals in the pre-COVID and COVID (April 2020) periods. RESULTS: Among 52 individuals with TB disease, 24 (46%) received treatment during the COVID-19 pandemic. vDOT utilization significantly increased in the COVID period (18/24[75%]) compared to pre-COVID (12/28[43%], p = 0.02). Overall, median verified adherence was similar pre-COVID and COVID periods (65% versus 68%, respectively, p = 0.96). Adherence was significantly higher overall when using vDOT (median 86% [IQR 70-98%]) compared to DOT (median 59% [IQR 55-64%], p < 0.01); this improved adherence with vDOT was evident in both the pre-COVID (median 98% vs. 58%, p < 0.01) and COVID period (median 80% vs. 62%, p = 0.01). CONCLUSION: vDOT utilization increased during the COVID period and was more effective than in-person DOT at verifying ingestion of prescribed treatment.

Tuberculosis treatment adherence in the era of COVID-19.

BACKGROUND In-person directly observed therapy (DOT) is commonly used for tuberculosis (TB) treatment monitoring in the US, with increasing usage of video-DOT (vDOT). We evaluated the impact of COVID-19 on TB treatment adherence, and utilization and effectiveness of vDOT. METHODS We abstracted routinely collected data on individuals treated for TB disease in Baltimore, Maryland between April 2019 and April 2021. Our primary outcomes were to assess vDOT utilization and treatment adherence, defined as the proportion of prescribed doses (7 days/week) verified by observation (in-person versus video-DOT), comparing individuals in the pre- and post-COVID (April 2020) periods. RESULTS Among 52 individuals with TB disease, 24 (46%) received treatment during the COVID-19 pandemic. vDOT utilization significantly increased post-COVID (18/24[75%]) compared to pre-COVID (12/28[43%], p=0.02). Overall, median verified adherence was similar pre- and post-COVID (65% versus 68%, respectively, p=0.96). Adherence was significantly higher overall when using vDOT (median 86% [IQR 70-98%]) compared to DOT (median 59% [IQR 55%-64%], p<0.01); this improved adherence with vDOT was evident in both the pre-COVID (median 98% vs 58%, p<0.01) and post-COVID period (median 80% vs 62%, p=0.01). CONCLUSION vDOT utilization increased post-COVID and was more effective than in-person DOT at verifying ingestion of prescribed treatment.

Programmatic Adoption and Implementation of Video-Observed Therapy in Minnesota: Prospective Observational Cohort Study.

BACKGROUND: In-person directly observed therapy (DOT) is standard of care for tuberculosis (TB) treatment adherence monitoring in the US, with increasing use of video-DOT (vDOT). In Minneapolis, vDOT became available in 2019. OBJECTIVE: In this paper, we aimed to evaluate the use and effectiveness of vDOT in a program setting, including comparison of verified adherence among those receiving vDOT and in-person DOT. We also sought to understand the impact of COVID-19 on TB treatment adherence and technology adoption. METHODS: We abstracted routinely collected data on individuals receiving therapy for TB in Minneapolis, MN, between September 2019 and June 2021. Our primary outcomes were to assess vDOT use and treatment adherence, defined as the proportion of prescribed doses (7 days per week) verified by observation (in person versus video-DOT), and to compare individuals receiving therapy in the pre-COVID-19 (before March 2020), and post-COVID-19 (after March 2020) periods; within the post-COVID-19 period, we evaluated early COVID-19 (March-August 2020), and intra-COVID-19 (after August 2020) periods. RESULTS: Among 49 patients with TB (mean age 41, SD 19; n=27, 55% female and n=47, 96% non-US born), 18 (36.7%) received treatment during the post-COVID-19 period. Overall, verified adherence (proportion of observed doses) was significantly higher when using vDOT (mean 81%, SD 17.4) compared to in-person DOT (mean 54.5%, SD 10.9; P=.001). The adoption of vDOT increased significantly from 35% (11/31) of patients with TB in the pre-COVID-19 period to 67% (12/18) in the post-COVID-19 period (P=.04). Consequently, overall verified (ie, observed) adherence among all patients with TB in the clinic improved across the study periods (56%, 67%, and 79%, P=.001 for the pre-, early, and intra-COVID-19 periods, respectively). CONCLUSIONS: vDOT use increased after the COVID-19 period, was more effective than in-person DOT at verifying ingestion of prescribed treatment, and led to overall increased verified adherence in the clinic despite the onset of the COVID-19 pandemic.

Projected Impact of Expanded Long-Acting Injectable PrEP Use Among Men Who Have Sex With Men on Local HIV Epidemics.

BACKGROUND: Pre-exposure prophylaxis (PrEP) is a key component in helping to reduce HIV incidence in the United States. Long-acting injectable (LAI) PrEP is a new alternative to oral PrEP; its potential to affect local HIV epidemics remains unclear. METHODS: The Johns Hopkins HIV Economic Epidemiological model (JHEEM) is a dynamic model of HIV transmission in 32 US urban areas. We used JHEEM to project the HIV incidence among men who have sex with men (MSM) from 2020 to 2030 under a range of interventions aimed at increasing PrEP use. RESULTS: In the absence of any intervention (ie, current levels of oral PrEP and HIV care engagement), we projected a 19% reduction (95% credible interval, CrI 1% to 36%) in HIV incidence among MSM from 2020 to 2030 across all 32 cities. Adding 10% LAI PrEP uptake (above a base case of all oral PrEP) reduced the incidence by 36% (95% CrI 23% to 50%) by year 2030. This effect varied between cities, ranging from 22% in Atlanta to 51% in San Francisco. At 25% additional LAI PrEP uptake, this incidence reduction increased to 54% (95% CrI 45% to 64%). Reductions in incidence after introducing LAI PrEP were driven primarily by increased uptake and sustained usage rather than increased efficacy. CONCLUSIONS: LAI PrEP has the potential to substantially reduce HIV incidence among MSM, particularly if it increases PrEP uptake and continued use beyond existing levels. Because potential effects vary by city, the effectiveness of expanding PrEP use is dependent on local dynamics.

Evaluation of the Latent Tuberculosis Care Cascade Among Public Health Clinics in the United States.

BACKGROUND: Tuberculosis (TB) elimination within the United States will require scaling up TB preventive services. Many public health departments offer care for latent tuberculosis infection (LTBI), although gaps in the LTBI care cascade are not well quantified. An understanding of these gaps will be required to design targeted public health interventions. METHODS: We conducted a cohort study through the Tuberculosis Epidemiologic Studies Consortium (TBESC) within 15 local health department (LHD) TB clinics across the United States. Data were abstracted on individuals receiving LTBI care during 2016-2017 through chart review. Our primary objective was to quantify the LTBI care cascade, beginning with LTBI testing and extending through treatment completion. RESULTS: Among 23 885 participants tested by LHDs, 46% (11 009) were male with a median age of 31 (interquartile range [IQR] 20-46). A median of 35% of participants were US-born at each site (IQR 11-78). Overall, 16 689 (70%) received a tuberculin skin test (TST), 6993 (29%) received a Quantiferon (QFT), and 1934 (8%) received a T-SPOT.TB; 5% (1190) had more than one test. Among those tested, 2877 (12%) had at least one positive test result (3% among US-born, and 23% among non-US-born, P < .01). Of 2515 (11%) of the total participants diagnosed with LTBI, 1073 (42%) initiated therapy, of whom 817 (76%) completed treatment (32% of those with LTBI diagnosis). CONCLUSIONS: Significant gaps were identified along the LTBI care cascade, with less than half of individuals diagnosed with LTBI initiating therapy. Further research is needed to better characterize the factors impeding LTBI diagnosis, treatment initiation, and treatment completion.

Estimated Transmission Outcomes and Costs of SARS-CoV-2 Diagnostic Testing, Screening, and Surveillance Strategies Among a Simulated Population of Primary School Students.

Importance: In addition to illness, the COVID-19 pandemic has led to historic educational disruptions. In March 2021, the federal government allocated $10 billion for COVID-19 testing in US schools. Objective: Costs and benefits of COVID-19 testing strategies were evaluated in the context of full-time, in-person kindergarten through eighth grade (K-8) education at different community incidence levels. Design, Setting, and Participants: An updated version of a previously published agent-based network model was used to simulate transmission in elementary and middle school communities in the United States. Assuming dominance of the delta SARS-CoV-2 variant, the model simulated an elementary school (638 students in grades K-5, 60 staff) and middle school (460 students grades 6-8, 51 staff). Exposures: Multiple strategies for testing students and faculty/staff, including expanded diagnostic testing (test to stay) designed to avoid symptom-based isolation and contact quarantine, screening (routinely testing asymptomatic individuals to identify infections and contain transmission), and surveillance (testing a random sample of students to identify undetected transmission and trigger additional investigation or interventions). Main Outcomes and Measures: Projections included 30-day cumulative incidence of SARS-CoV-2 infection, proportion of cases detected, proportion of planned and unplanned days out of school, cost of testing programs, and childcare costs associated with different strategies. For screening policies, the cost per SARS-CoV-2 infection averted in students and staff was estimated, and for surveillance, the probability of correctly or falsely triggering an outbreak response was estimated at different incidence and attack rates. Results: Compared with quarantine policies, test-to-stay policies are associated with similar model-projected transmission, with a mean of less than 0.25 student days per month of quarantine or isolation. Weekly universal screening is associated with approximately 50% less in-school transmission at one-seventh to one-half the societal cost of hybrid or remote schooling. The cost per infection averted in students and staff by weekly screening is lowest for schools with less vaccination, fewer other mitigation measures, and higher levels of community transmission. In settings where local student incidence is unknown or rapidly changing, surveillance testing may detect moderate to large in-school outbreaks with fewer resources compared with schoolwide screening. Conclusions and Relevance: In this modeling study of a simulated population of primary school students and simulated transmission of COVID-19, test-to-stay policies and/or screening tests facilitated consistent in-person school attendance with low transmission risk across a range of community incidence. Surveillance was a useful reduced-cost option for detecting outbreaks and identifying school environments that would benefit from increased mitigation.

Navigating Human Immunodeficiency Virus and Primary Care Concerns Specific to the Transgender and Gender-Nonbinary Population.

Human immunodeficiency virus (HIV) prevention and treatment remain critically important to outpatient care among transgender and gender-nonbinary individuals. Epidemiologically, trans men and trans women are significantly more likely to have HIV compared with all adults of reproductive age. Here, we provide an overview of unique primary care considerations affecting transgender and gender-nonbinary individuals, including screening and treatment of HIV and other sexually transmitted infections as well as cancer screening and fertility preservation options. We also seek to review current literature and clinical practice guidelines related to drug-drug interactions between antiretroviral therapy (ART) and gender-affirming hormonal therapy (GAHT). In short, integrase strand transfer inhibitor-based therapy is not expected to have significant drug interactions with most GAHT and is preferred in most transgender individuals, including those on GAHT. Clinicians should also remain aware of current GAHT regimens and consider tailoring ART and GAHT to reduce cardiovascular and other risk factors.

Diagnostic Accuracy of Urine Lipoarabinomannan Testing in Early Morning Urine versus Spot Urine for Diagnosis of Tuberculosis among People with HIV.

The Fujifilm SILVAMP TB LAM (FujiLAM) assay offers improved sensitivity compared to Determine TB LAM Ag (AlereLAM) for detecting tuberculosis (TB) among people with HIV. Here, we examined the diagnostic value of FujiLAM testing on early morning urine versus spot urine and the added value of a two-sample strategy. We assessed the diagnostic accuracy of FujiLAM on cryopreserved urine samples collected and stored as part of a prospective cohort of adults with HIV presenting for antiretroviral treatment in Ghana. We compared FujiLAM sensitivity and specificity in spontaneously voided urine samples collected at inclusion (spot urine) versus in the first voided early morning urine (morning urine) and for a one (spot urine) versus two samples (spot and morning urine) strategy. Diagnostic accuracy was determined against both microbiological (using sputum culture and Xpert MTB/RIF testing of sputum and urine to confirm TB) and composite reference standards (including microbiologically confirmed and probable TB cases). Paired urine samples of spot and morning urine were available for 389 patients. Patients had a median CD4 cell count of 176 cells/µL (interquartile range [IQR], 52 to 361). Forty-three (11.0%) had confirmed TB, and 19 (4.9%) had probable TB. Overall agreement for spot versus morning urine test results was 94.6% (kappa, 0.81). Compared to a microbiological reference standard, the FujiLAM sensitivity (95% confidence interval [CI]) was 67.4% (51.5 to 80.9) for spot and 69.8% (53.9 to 82.8) for morning urine, an absolute difference (95% CI) of 2.4% (-10.2 to 14.8). Specificity was 90.2% (86.5 to 93.1) versus 89.0% (85.2 to 92.1) for spot and morning urine, respectively, a difference of 1.2% (-3.7 to 1.4). A two-sample strategy increased FujiLAM sensitivity from 67.4% (51.5 to 80.9) to 74.4% (58.8 to 86.5), a difference of 7.0% (-3.0 to 16.9), while specificity decreased from 90.2% (86.5 to 93.1) to 87.3% (83.3 to 90.6), a difference of -2.9% (-4.9 to -0.8). This study indicates that FujiLAM testing performs equivalently on spot and early morning urine samples. Sensitivity could be increased with a two-sample strategy but at the risk of lower specificity. These data can inform future guidelines and clinical practice. IMPORTANCE This study indicates that FujiLAM testing performs equivalently on spot and early morning urine samples for detecting tuberculosis among people with HIV. Sensitivity could be increased with a two-sample strategy but at the risk of lower specificity. These data can inform future guidelines and clinical practice around FujiLAM.

Potential Effects of the Coronavirus Disease 2019 (COVID-19) Pandemic on Human Immunodeficiency Virus (HIV) Transmission: A Modeling Study in 32 US Cities.

BACKGROUND: The degree to which the 2019 novel coronavirus disease (COVID-19) pandemic will affect the US human immunodeficiency virus (HIV) epidemic is unclear. METHODS: We used the Johns Hopkins Epidemiologic and Economic Model to project HIV infections from 2020 to 2025 in 32 US metropolitan statistical areas (MSAs). We sampled a range of effects of the pandemic on sexual transmission (0-50% reduction), viral suppression among people with HIV (0-40% reduction), HIV testing (0-50% reduction), and pre-exposure prophylaxis use (0-30% reduction), and indexed reductions over time to Google Community Mobility Reports. RESULTS: Simulations projected reported diagnoses would drop in 2020 and rebound in 2021 or 2022, regardless of underlying incidence. If sexual transmission normalized by July 2021 and HIV care normalized by January 2022, we projected 1161 (1%) more infections from 2020 to 2025 across all 32 cities than if COVID-19 had not occurred. Among "optimistic" simulations in which sexual transmission was sharply reduced and viral suppression was maintained we projected 8% lower incidence (95% credible interval: 14% lower to no change). Among "pessimistic" simulations where sexual transmission was largely unchanged but viral suppression fell, we projected 11% higher incidence (1-21% higher). MSA-specific projections are available at www.jheem.org?covid. CONCLUSIONS: The effects of COVID-19 on HIV transmission remain uncertain and differ between cities. Reported diagnoses of HIV in 2020-2021 are likely to correlate poorly with underlying incidence. Minimizing disruptions to HIV care is critical to mitigating negative effects of the COVID-19 pandemic on HIV transmission.

What Will It Take to End HIV in the United States? : A Comprehensive, Local-Level Modeling Study.

BACKGROUND: The Ending the HIV Epidemic (EHE) initiative aims to reduce incident HIV infections by 90% over a span of 10 years. The intensity of interventions needed to achieve this for local epidemics is unclear. OBJECTIVE: To estimate the effect of HIV interventions at the city level. DESIGN: A compartmental model of city-level HIV transmission stratified by age, race, sex, and HIV risk factor was developed and calibrated. SETTING: 32 priority metropolitan statistical areas (MSAs). PATIENTS: Simulated populations in each MSA. INTERVENTION: Combinations of HIV testing and preexposure prophylaxis (PrEP) coverage among those at risk for HIV, plus viral suppression in persons with diagnosed HIV infection. MEASUREMENTS: The primary outcome was the projected reduction in incident cases from 2020 to 2030. RESULTS: Absent intervention, HIV incidence was projected to decrease by 19% across all 32 MSAs. Modest increases in testing (1.25-fold per year), PrEP coverage (5 percentage points), and viral suppression (10 percentage points) across the population could achieve reductions of 34% to 67% by 2030. Twenty-five percent PrEP coverage, testing twice a year on average, and 90% viral suppression among young Black and Hispanic men who have sex with men (MSM) achieved similar reductions (13% to 68%). Including all MSM and persons who inject drugs could reduce incidence by 48% to 90%. Thirteen of 32 MSAs could achieve greater than 90% reductions in HIV incidence with large-scale interventions that include heterosexuals. A web application with location-specific results is publicly available (www.jheem.org). LIMITATION: The COVID-19 pandemic was not represented. CONCLUSION: Large reductions in HIV incidence are achievable with substantial investment, but the EHE goals will be difficult to achieve in most locations. An interactive model that can help policymakers maximize the effect in their local environments is presented. PRIMARY FUNDING SOURCE: National Institutes of Health.

Infectious Diseases Learning Unit: Understanding Advances in the Treatment of Latent Tuberculosis Infection Among People With Human Immunodeficiency Virus.

Tuberculosis (TB) remains the leading cause of death among people with human immunodeficiency virus (PWH). The diagnosis of latent TB infection (LTBI) and treatment with TB preventative therapy (TPT) can reduce morbidity and mortality in this population. Historically, isoniazid has been recommended for TPT in PWH due to the absence of drug-drug interactions with most antiretroviral therapy (ART). However, newer rifamycin-based regimens are safer, shorter in duration, associated with improved adherence, and may be as or more effective than isoniazid TPT. Current guidelines have significant heterogeneity in their recommendations for TPT regimens and acceptability of drug interactions with modern ART. In this Infectious Diseases learning unit, we review common questions on diagnosis, treatment, and drug interactions related to the management of LTBI among PWH.

Using Innovation to Address Adolescent and Young Adult Health Disparities in Pelvic Inflammatory Disease: Design of the Technology Enhanced Community Health Precision Nursing (TECH-PN) Trial.

New approaches to pelvic inflammatory disease (PID) care among adolescents and young adults (AYAs) that optimize self-care and personalize treatment are warranted to address age and racial-ethnic PID-related health disparities. Here we describe the 13-month preliminary feasibility and acceptability outcomes of recruitment, retention, and intervention delivery for Technology Enhanced Community Health Precision Nursing (TECH-PN) randomized controlled trial. Urban AYAs 13-25 years assigned female sex at birth with acute mild-moderate PID provided baseline and follow-up interview data and vaginal specimens for sexually transmitted infection (STI), cytokine, and microbiota assessment. All participants received medications and text-messaging support. Participants were block randomized to either control or intervention. Control participants received 1 community nursing visit with self-management for interim care per national guidelines. Intervention participants received unlimited precision care services driven by interim STI and macrolide resistance testing results by an advanced practice provider. In the first 13 months, 75.2% patients were eligible, and 76.1% of eligible patients enrolled. Of the participants, 94% completed the intervention and 96%, 91%, and 89%, respectively, completed their 14-, 30-, and 90-day visits. Baseline laboratory results revealed infection rates that were highest for Mycoplasma genitalium (45%) followed by Chlamydia trachomatis (31%). Preliminary enrollment, STI, intervention delivery, and retention data demonstrate the feasibility and acceptability of the TECH-PN intervention and support rationale for precision care for PID among urban AYAs. ClinicalTrials.gov Identifier. NCT03828994.

SARS-CoV-2 testing strategies to contain school-associated transmission: model-based analysis of impact and cost of diagnostic testing, screening, and surveillance.

Background: In March 2021, the Biden administration allocated $10 billion for COVID-19 testing in schools. We evaluate the costs and benefits of testing strategies to reduce the infection risks of full-time in-person K-8 education at different levels of community incidence. Methods: We used an agent-based network model to simulate transmission in elementary and middle school communities, parameterized to a US school structure and assuming dominance of the delta COVID-19 variant. We assess the value of different strategies for testing students and faculty/staff, including expanded diagnostic testing ("test to stay" policies that take the place of isolation for symptomatic students or quarantine for exposed classrooms); screening (routinely testing asymptomatic individuals to identify infections and contain transmission); and surveillance (testing a random sample of students to signaling undetected transmission and trigger additional investigation or interventions). Main outcome measures: We project 30-day cumulative incidence of SARS-CoV-2 infection; proportion of cases detected; proportion of planned and unplanned days out of school; and the cost of testing programs and of childcare costs associated with different strategies. For screening policies, we further estimate cost per SARS-CoV-2 infection averted in students and staff, and for surveillance, probability of correctly or falsely triggering an outbreak response at different incidence and attack rates. Results: Accounting for programmatic and childcare costs, "test to stay" policies achieve similar model-projected transmission to quarantine policies, with reduced overall costs. Weekly universal screening prevents approximately 50% of in-school transmission, with a lower projected societal cost than hybrid or remote schooling. The cost per infection averted in students and staff by weekly screening is lower for older students and schools with higher mitigation and declines as community transmission rises. In settings where local student incidence is unknown or rapidly changing, surveillance may trigger detection of moderate-to-large in-school outbreaks with fewer resources compared to screening. Conclusions: "Test to stay" policies and/or screening tests can facilitate consistent in-person school attendance with low transmission risk across a range of community incidence. Surveillance may be a useful reduced-cost option for detecting outbreaks and identifying school environments that may benefit from increased mitigation.