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Of new sexually transmitted infections (STIs) in the United States, 50% occur among youth aged 15 to 24 years. Previous studies among youth with HIV (YHIV) do not distinguish STI trends among individuals with perinatally (YPHIV) and nonperinatally (YNPHIV) acquired HIV.Among 3 Adolescent Medicine Trials Network for HIV/AIDS Interventions (ATN) studies conducted between 2009 and 2015, we estimated incident diagnoses of trichomonal, bacterial, viral, and overall STIs stratified by sex assigned at birth, mode of HIV acquisition (perinatal [YPHIV] and nonperinatal [YNPHIV]), age (13-17 and 18-24 years), CD4 count (200, 200-499, and ≥500/μL), and HIV viral load (VL) (400 and ≥400 copies/mL).Among 3131 YHIV, across the 3 studies, mean (SD) age was 20.6 (2.6) years, 888 (28%) were female, 2498 (80%) had nonperinatal HIV acquisition recorded, and 2298 (73%) were African American/Black. Mean follow-up was 0.9 (0.3) years. Compared with YPHIV, YNPHIV spent less person-time with VL400 copies/mL (47% vs. 53%) and more time off antiretroviral therapy (49% vs. 15%), and had higher overall STI rates (males, 65.9 vs. 8.5/100 person-years [PY]; females, 54.7 vs. 17.2/100 PY). Among YPHIV, bacterial STIs were higher during person-time spent with VL ≥400 vs.400 copies/mL (male YPHIV, 10.9 vs. 0.6/100 PY; female YPHIV, 11.2 vs. 2.9/100 PY); no difference was observed among YNPHIV, which may be due to concurrent acquisition of HIV and other STIs and limited follow-up.Compared with YPHIV, YNPHIV spent less time on antiretroviral therapy and virologically suppressed; YNPHIV also had higher STI diagnosis rates. Very high STI diagnosis rates among YHIV, including among those without virologic suppression, highlight the importance of youth-focused efforts to support durable virologic suppression and identify and treat STIs.

A Pregnant Woman with Fever, Abdominal Pain, and Headache A 33-year-old pregnant woman with ulcerative colitis presented at 10 weeks of gestation with fever, nausea, vomiting, abdominal pain, and h...

Background Isolation of hospitalized persons under investigation (PUIs) for coronavirus disease 2019 (COVID-19) reduces nosocomial transmission risk. Efficient evaluation of PUIs is needed to preserve scarce healthcare resources. We describe the development, implementation, and outcomes of an inpatient diagnostic algorithm and clinical decision support system (CDSS) to evaluate PUIs. Methods We conducted a pre-post study of CORAL (COvid Risk cALculator), a CDSS that guides frontline clinicians through a risk-stratified COVID-19 diagnostic workup, removes transmission-based precautions when workup is complete and negative, and triages complex cases to infectious diseases (ID) physician review. Before CORAL, ID physicians reviewed all PUI records to guide workup and precautions. After CORAL, frontline clinicians evaluated PUIs directly using CORAL. We compared pre- and post-CORAL frequency of repeated severe acute respiratory syndrome coronavirus 2 nucleic acid amplification tests (NAATs), time from NAAT result to PUI status discontinuation, total duration of PUI status, and ID physician work hours, using linear and logistic regression, adjusted for COVID-19 incidence. Results Fewer PUIs underwent repeated testing after an initial negative NAAT after CORAL than before CORAL (54% vs 67%, respectively; adjusted odd ratio, 0.53 [95% confidence interval, .44–.63]; P Conclusions CORAL is an efficient and effective CDSS to guide frontline clinicians through the diagnostic evaluation of PUIs and safe discontinuation of precautions.

The Adolescent Medicine Trials Network for HIV/AIDS Interventions is evaluating treatment adherence interventions (AI) to improve virologic suppression (VS) among youth with HIV (YWH). Using a microsimulation model, we compared two strategies: standard-of-care (SOC) and a hypothetical 12-month AI that increased cohort-level VS in YWH in care by an absolute ten percentage points and cost $100/month/person. Projected outcomes included primary HIV transmissions, deaths and life-expectancy, lifetime HIV-related costs, and incremental cost-effectiveness ratios (ICERs, $/quality-adjusted life-year [QALY]). Compared to SOC, AI would reduce HIV transmissions by 15% and deaths by 12% at 12 months. AI would improve discounted life expectancy/person by 8 months at an added lifetime cost/person of $5,300, resulting in an ICER of $7,900/QALY. AI would be cost-effective at $2,000/month/person or with efficacies as low as a 1 percentage point increase in VS. YWH-targeted adherence interventions with even modest efficacy could improve life expectancy, prevent onward HIV transmissions, and be cost-effective.La Red de Ensayos Médicos sobre Adolescentes para Realizar Intervenciones sobre el VIH/SIDA está evaluando intervenciones de adherencia (IAs) al tratamiento para mejorar la supresión virológica (SV) entre los jóvenes con VIH (JCV). Usando un modelo de microsimulación, comparamos dos estrategias: cuidado convencional (CC) y una intervención de adherencia hipotética durando 12 meses que aumentaría la SV a nivel de cohorte entre JCV en tratamiento por 10 puntos de porcentuales y que costaría US$ 100/mes/persona. Resultados proyectados incluyeron transmisiones de VIH primarias, muertes y esperanza de vida, costos de por vida asociados con el VIH, y razones incrementales de costo-efectividad (RICEs, $/año de vida ajustado por la calidad [AVAC]). Comparado al CC, la IA reduciría transmisiones de VIH por 15% y muertes por 12% a los 12 meses. La IA mejoraría esperanza de vida descontada/persona por 8 meses a un costo de por vida adicional/persona de US$ 5.300, resultando en una RICE de US$ 7.900/AVAC. La IA sería costo-efectiva a un costo de US$ 2.000/mes/persona o si mejorara SV por al menos un punto porcentual. Intervenciones de adherencia dirigidas a jóvenes con una eficacia incluso modesta podrían mejorar esperanza de vida, prevenir transmisiones de VIH, y ser costo-efectivas.

Background While studies from large cities affected by coronavirus disease 2019 (COVID-19) have reported on the prevalence of SARS-CoV-2 in the context of universal testing during admission for delivery, the patient demographic, social and clinical factors associated with SARS-CoV-2 infection in pregnant women are not fully understood. Objective To evaluate the epidemiological factors associated with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in women admitted for labour and delivery, in the context of universal screening at four Boston-area hospitals. Methods In this prospective cohort study, we reviewed the health records of all women admitted for labour and delivery at four hospitals from the largest health system in Massachusetts between 19 April 2020 and 27 June 2020. We calculated the risk of SARS-CoV-2 infection, including asymptomatic infection. We calculated associations between SARS-CoV-2 infection and demographic and clinical characteristics. Results A total of 93 patients (3.2%, 95% confidence interval 2.5, 3.8) tested positive for SARS-CoV-2 infection on admission for labour and delivery out of 2945 patients included in the analysis; 80 (86.0%) of the patients who tested positive were asymptomatic at the time of testing. Factors associated with SARS-CoV-2 infection included the following: younger age, obesity, African American or Hispanic race/ethnicity, residence in heavily affected communities (as measured in cases reported per capita), presence of a household member with known SARS-CoV-2 infection, non-health care essential worker occupation and MassHealth or Medicaid insurance compared to commercial insurance. 93.8% of patients testing positive for SARS-CoV-2 on admission had one or more identifiable factors associated with disease acquisition. Conclusions In this large sample of deliveries during the height of the surge in infections during the spring of 2020, SARS-CoV-2 infection was largely concentrated in patients with distinct demographic characteristics, those largely from disadvantaged communities. Racial disparities seen in pregnancy persist with respect to SARS-CoV-2 infection.

To compare the unit and total costs of three models of ART care for mother-infant pairs during the postpartum phase from provider and patient's perspectives: (i) local standard of care with women in general ART services and infants at well-baby clinics; (ii) women and infants continue to receive care through an integrated maternal and child care approach during the postpartum breastfeeding period; and (iii) referral of women directly to community adherence clubs with their infants receiving care at well-baby clinics.Capital and recurrent cost data (relating to buildings, furniture, equipment, personnel, overheads, maintenance, medication, diagnostic tests and immunisations) were collected from a provider's perspective at six sites in Cape Town, South Africa. Patient time, collected via time-and-motion observation and questionnaires, was used to estimate patient perspective costs and is comprised of lost productivity time, time spent travelling and the direct cost of travelling.The cost of postpartum ART visits under models I, II and III was US $13, US $10 and US $7 per visit for a mother-infant pair, respectively, in 2018 US$. The annual costs for the mother-infant pair utilising the average visit frequencies (a mean of 4.5, 6.9 and 6.7 visits postpartum for models I, II and III, respectively) including costs for infant immunisations, visits, medication and diagnostic tests for both mothers and infants were: I - US $222, II - US $335 and III - US $249. Sensitivity analysis to assess the impact of visit frequency on visit cost showed that Model I annual costs would be most costly if visit frequency was equalised.This comparative analysis of three models of care provides novel data on unit costs and insight into the costs to provide ART and care to mother-infant pairs during the delicate postpartum phase. These costs may be used to help make decisions around integrated services models and differentiated service delivery for postpartum WLH and their children.Comparer le coût et unitaire et total de trois modèles de soins ART pour les paires mère-enfant pendant la phase post-partum selon les perspectives du fournisseur et du patient: (I) - normes locales des soins avec les femmes dans les services généraux de l'ART et les nourrissons dans les cliniques de bien-être pour bébés; (II) - les femmes et les nourrissons continuent de recevoir des soins via une approche intégrée de soins maternels et infantiles pendant la période d'allaitement post-partum; et (III) - orientation des femmes directement vers les clubs d'adhésion communautaires, leurs nourrissons recevant des soins dans les cliniques de bien-être pour bébés pour bébés. MÉTHODES: Les données sur les coûts d'investissement et les coûts récurrents (relatifs aux bâtiments, au mobilier, à l'équipement, au personnel, aux frais généraux, à l'entretien, aux médicaments, aux tests de diagnostic et aux vaccinations) ont été recueillies selon le point de vue du prestataire sur six sites à Cape Town, en Afrique du Sud. Le temps du patient, recueilli via l'observation du temps et des mouvements et des questionnaires, a été utilisé pour estimer les coûts selon le point de vue du patient, et comprend le temps de productivité perdu, le temps passé en déplacement et le coût direct du déplacement. RÉSULTATS: Le coût des visites ART post-partum dans les modèles I, II et III était respectivement de 13 USD, 10 USD et 7 USD par visite pour une paire mère-enfant en USD de 2018. Les coûts annuels pour la paire mère-enfant en utilisant la fréquence moyenne des visites (une moyenne de 4,5 ; 6,9 et 6,7 visites post-partum pour les modèles I, II et III respectivement), y compris les coûts des vaccinations infantiles, des visites, des médicaments et des tests diagnostiques pour les mères et les nourrissons étaient: I - 222 USD, II - 335 USD et III - 249 USD. L'analyse de sensibilité pour évaluer l'impact de la fréquence des visites sur le coût des visites a montré que les coûts annuels du modèle I seraient les plus élevés si la fréquence des visites était égalisée.Cette analyse comparative de trois modèles de soins fournit de nouvelles données sur les coûts unitaires et un aperçu des coûts de fourniture de l’ART et de soins aux paires mère-enfant pendant la phase délicate du post-partum. Ces coûts peuvent être utilisés pour aider à la prise des décisions concernant les modèles de services intégrés et la prestation de services différenciés pour les femmes en période de post-partum et leurs enfants.

Scaling up of point-of-care testing (POCT) for early infant diagnosis of HIV (EID) could reduce the large gap in infant testing. However, suboptimal POCT EID could have limited impact and potentially high avoidable costs. This study models the cost-effectiveness of a quality assurance system to address testing performance and screening interruptions, due to, for example, supply stockouts, in Kenya, Senegal, South Africa, Uganda and Zimbabwe, with varying HIV epidemics and different health systems.We modelled a quality assurance system-raised EID quality from suboptimal levels: that is, from misdiagnosis rates of 5%, 10% and 20% and EID testing interruptions in months, to uninterrupted optimal performance (98.5% sensitivity, 99.9% specificity). For each country, we estimated the 1-year impact and cost-effectiveness (US$/DALY averted) of improved scenarios in averting missed HIV infections and unneeded HIV treatment costs for false-positive diagnoses.The modelled 1-year costs of a national POCT quality assurance system range from US$ 69 359 in South Africa to US$ 334 341 in Zimbabwe. At the country level, quality assurance systems could potentially avert between 36 and 711 missed infections (i.e. false negatives) per year and unneeded treatment costs between US$ 5808 and US$ 739 030.The model estimates adding effective quality assurance systems are cost-saving in four of the five countries within the first year. Starting EQA requires an initial investment but will provide a positive return on investment within five years by averting the costs of misdiagnoses and would be even more efficient if implemented across multiple applications of POCT.L'intensification du dépistage au point des soins (DPS) pour le diagnostic précoce du VIH chez le nourrisson (DPVN) pourrait réduire le grand écart dans le dépistage des nourrissons. Cependant, un DPVN DPS sous-optimal pourrait avoir un impact limité et des coûts évitables potentiellement élevés. Cette étude modélise la rentabilité d'un système d'assurance qualité pour traiter les performances des tests et les interruptions de dépistage, dues par exemple à des ruptures de stock, au Kenya, au Sénégal, en Afrique du Sud, en Ouganda et au Zimbabwe, avec des épidémies variables du VIH et des systèmes de santé différents. MÉTHODES: Nous avons modélisé une qualité de DPVN soulevée par le système d'assurance qualité à partir de niveaux sous-optimaux: c'est-à-dire des taux d'erreurs de diagnostic de 5%, 10% et 20% et des interruptions des tests de DPVN en mois, à des performances optimales ininterrompues (sensibilité de 98,5%, spécificité de 99,9%). Pour chaque pays, nous avons estimé l'impact sur un an et la rentabilité (en USD/DALY évitée) de scénarios améliorés pour éviter les infections à VIH manquées et les coûts inutiles de traitement du VIH pour les diagnostics faux positifs. RÉSULTATS: Les coûts modélisés sur un an d'un système national d'assurance qualité DPS vont de 69.359 USD en Afrique du Sud à 334.341 USD au Zimbabwe. Au niveau des pays, les systèmes d'assurance de la qualité pourraient potentiellement éviter entre 36 et 711 infections manquées (c'est-à-dire des faux négatifs) par an et des coûts de traitement inutiles entre 5.808 et 739.030 USD.Le modèle estime que l'ajout de systèmes d'assurance qualité efficaces permet de réaliser des économies dans quatre des cinq pays au cours de la première année. Le lancement de l'assurance qualité nécessite un investissement initial, mais fournira un retour sur investissement positif dans les cinq ans en évitant les coûts des diagnostics erronés et serait encore plus efficace s'il était mis en œuvre dans plusieurs applications de DPS.

We describe an approach to the evaluation and isolation of hospitalized persons under investigation (PUIs) for coronavirus disease 2019 (COVID-19) at a large US academic medical center. Only a small proportion (2.9%) of PUIs with 1 or more repeated severe acute respiratory coronavirus virus 2 (SARS-CoV-2) nucleic acid amplification tests (NAATs) after a negative NAAT were diagnosed with COVID-19.

Background Of new HIV infections in the US, 20% occur among young men who have sex with men (YMSM, ages 13–24), but >50% of YMSM with HIV are unaware of their status. Using Adolescent Medicine Trials Network for HIV/AIDS Interventions (ATN) data, we projected the clinical benefit and cost-effectiveness of frequent HIV screening among high-risk YMSM from age 15. Methods Using a mathematical simulation, we examined 3 screening strategies: Yearly, 6-monthly, and 3-monthly, each in addition to the Status quo (SQ, 0.7–10.3% screened/year, stratified by age). We used published data (YMSM-specific when available) including: HIV incidences (0.91–6.41/100PY); screen acceptance (80%), linkage-to-care/antiretroviral therapy (ART) initiation (76%), HIV transmission (0.3–86.1/100PY, by HIV RNA), monthly ART costs ($2290-$3780), and HIV per-screen costs ($38). Projected outcomes included CD4 count at diagnosis, primary HIV transmissions from ages 15–30, quality-adjusted life expectancy, costs, and incremental cost-effectiveness ratios (ICERs, $/quality-adjusted life-year saved [QALY]; threshold ≤$100 000/QALY). Results Compared to SQ, all strategies increased projected CD4 at diagnosis (296 to 477–515 cells/µL) and quality-adjusted life expectancy from age 15 (44.4 to 48.3–48.7 years) among YMSM acquiring HIV. Compared to SQ, all strategies increased discounted lifetime cost for the entire population ($170 800 to $178 100-$185 000/person). Screening 3-monthly was cost-effective (ICER: $4500/QALY) compared to SQ and reduced primary transmissions through age 30 by 40%. Results were most sensitive to transmission rates; excluding the impact of transmissions, screening Yearly was ≤$100 000/QALY (ICER: $70 900/QALY). Conclusions For high-risk YMSM in the US, HIV screening 3-monthly compared to less frequent screening will improve clinical outcomes and be cost-effective.

Supplemental Digital Content is Available in the Text., Background: To improve early infant HIV diagnosis (EID) programs, options include replacing laboratory-based tests with point-of-care (POC) assays or investing in strengthened systems for sample transport and result return. Setting: We used the CEPAC-Pediatric model to examine clinical benefits and costs of 3 EID strategies in Zimbabwe for infants 6 weeks of age. Methods: We examined (1) laboratory-based EID (LAB), (2) strengthened laboratory-based EID (S-LAB), and (3) POC EID (POC). LAB/S-LAB and POC assays differed in sensitivity (LAB/S-LAB 100%, POC 96.9%) and specificity (LAB/S-LAB 99.6%, POC 99.9%). LAB/S-LAB/POC algorithms also differed in: probability of result return (79%/91%/98%), time until result return (61/53/1 days), probability of initiating antiretroviral therapy (ART) after positive result (52%/71%/86%), and total cost/test ($18.10/$30.47/$30.71). We projected life expectancy (LE) and average lifetime per-person cost for all HIV-exposed infants. We calculated incremental cost-effectiveness ratios (ICERs) from discounted (3%/year) LE and costs in $/year-of-life saved (YLS), defining cost effective as an ICER

BACKGROUND Adolescents and young adults (AYA) with HIV experience poorer health outcomes compared with adults. To improve care for AYA with HIV, information about patterns of costly health care resource utilization is needed. METHODS Among 13-30 year olds in the US HIV Research Network, we stratified outpatient visits, emergency department (ED) visits, and inpatient days/person-year (PY) by HIV acquisition model [perinatal (PHIVY) and nonperinatal (NPHIVY)], age (13-17, 18-23, and 24-30 years), CD4 strata (

SARS-CoV-2 transmission in K-12 schools was rare during in 2020-2021; few studies included CDC-recommended screening of asymptomatic individuals. We conduct a prospective observational study of SARS-CoV-2 screening in a mid-sized suburban public school district, to evaluate the incidence of asymptomatic COVID-19, document frequency of in-school transmission, and characterize barriers and facilitators to asymptomatic screening in schools. Staff and students undergo weekly pooled testing using home-collected saliva samples. Identification of >1 case in a school prompts investigation for in-school transmission and enhancement of safety strategies. With layered mitigation measures, in-school transmission even before student or staff vaccination is rare. Screening identifies a single cluster with in-school staff-to-staff transmission, informing decisions about in-person learning. The proportion of survey respondents self-reporting comfort with in-person learning before versus after implementation of screening increases. Costs exceed $260,000 for assays alone; staff and volunteers spend 135-145 hours per week implementing screening., Graphical Abstract, Reports of rare SARS-CoV-2 transmission in K-12 schools are limited by lack of asymptomatic screening. Doron et al. report that public-school screening for asymptomatic SARS-CoV-2 in 2020-21 provides valuable data about in-school transmission risk and informs decisions about in-person learning, but human and financial resource requirements are high.

IntroductionThe SARS-CoV-2 secondary attack rate (SAR) in schools is low when mitigation measures are adopted, Data on the relative impact of such strategies are limited. We evaluated the SARS-CoV-2 SAR in Massachusetts schools during 2020-21 and factors associated with transmission risk. MethodsIn a convenience sample of 25 Massachusetts public K-12 school districts, de-identified information about SARS-CoV-2 cases and their school-based contacts was reported using a standardized contact-tracing tool. Index cases were included if they were in school while infectious. SAR was defined as the proportion of in-school contacts acquiring SARS-CoV-2 infection and designated as possible or probable in-school transmission by school-based teams. We compared exposure-specific SAR using unadjusted risk ratios (RR) with 95% confidence intervals (CI); p-values were calculated using Fishers exact tests. ResultsEight districts (70 schools with >33,000 enrolled students) participated. There were 435 index cases and 1,771 school-based contacts (Table 1). Most contacts (1327/1771 [75%]) underwent SARS-CoV-2 testing and 39/1327 (2.9%) contacts tested positive. Of 39 positive contacts, 10 (25.6%) had clear out-of-school exposures and were deemed not in-school transmissions, so were excluded from further calculations. Twenty-nine (74.4%) contacts were deemed possible or probable in-school transmissions, resulting in an in-school SAR of 2.2%. Of the 29 in-school transmissions, 6 (20.7%) were staff-to-staff, 7 (24.1%) were staff-to-student, 3 (10.3%) were student-to-staff, and 13 (44.8%) were student-to-student; 6 (20.7%) occurred from index cases attending work/school while symptomatic. The unadjusted SAR (Table 2) was significantly higher if the index case was a staff member versus a student (RR 2.18, 95% CI 1.06-4.49; p=0.030), if the index case was identified via in-school contact tracing versus via school-based asymptomatic testing (RR 8.44, 95% CI 1.98-36.06; p=0.001), if the exposure occurred at lunch versus elsewhere (RR 5.74, 95% CI 2.11-15.63; p

BackgroundWhile CDC guidance for K-12 schools recommends indoor masking regardless of vaccination status, final decisions about masking in schools will be made at the local and state level. The impact of the removal of mask restrictions, however, on COVID-19 outcomes for elementary students, educators/staff, and their households is not well known.MethodsWe used a previously published agent-based dynamic transmission model of SARS-CoV-2 in K-12 schools to simulate an elementary school with 638 students across 12 scenarios: combinations of three viral infectiousness levels (reflecting wild-type virus, alpha variant, and delta variant) and four student vaccination levels (0%, 25%, 50% and 70% coverage). For each scenario, we varied observed community COVID-19 incidence (0 to 50 cases/100,000 people/day) and mitigation effectiveness (0-100% reduction to in-school secondary attack rate), and evaluated two outcomes over a 30 day period: (1) the probability of at least one in-school transmission, and (2) average increase in total infections among students, educators/staff, and their household members associated with moving from more to less intensive mitigation measures.ResultsOver 30 days in the simulated elementary school, the probability of at least one in-school SARS-CoV-2 transmission and the number of estimated additional infections in the immediate school community associated with changes in mitigation measures varied widely. In one scenario with the delta variant and no student vaccination, assuming that baseline mitigation measures of simple ventilation and handwashing reduce the secondary attack rate by 40%, if decision-makers seek to keep the monthly probability of an in-school transmission below 50%, additional mitigation (e.g., masking) would need to be added at a community incidence of approximately 2/100,000/day. Once students are vaccinated, thresholds shift substantially higher.LimitationsThe interpretation of model results should be limited by the uncertainty in many of the parameters, including the effectiveness of individual mitigation interventions and vaccine efficacy against the delta variant, and the limited scope of the model beyond the school community. Additionally, the assumed case detection rate (33% of cases detected) may be too high in areas with decreased testing capacity.ConclusionDespite the assumption of high adult vaccination, the risks of both in-school SARS-CoV-2 transmission and resulting infections among students, educators/staff, and their household members remain high when the delta variant predominates and students are unvaccinated. Mitigation measures or vaccinations for students can substantially reduce these risks. These findings underscore the potential role for responsive plans, where mitigation is deployed based on local COVID-19 incidence and vaccine uptake.

Summary Background New point-of-care (POC) assays for early infant HIV diagnosis are costlier than conventional total nucleic acid assays, but could increase access to testing, shorten time to results, and expedite initiation of antiretroviral therapy. We aimed to assess the clinical benefits and cost-effectiveness of incorporating these POC assays into early infant diagnosis programmes in Zimbabwe. Methods We used the Cost Effectiveness of Preventing AIDS Complications (CEPAC)—Pediatric model to examine the clinical benefits, costs, and cost-effectiveness of replacing conventional assays for early infant HIV diagnosis with POC assays at age 6 weeks in Zimbabwe. We simulated two strategies for early infant HIV diagnosis: conventional and POC. Modelled assays differed in sensitivity; specificity; time to, and probability of, return of results; and cost. Model outcomes included survival, life expectancy, and mean lifetime per-person treatment cost, which were reported separately for all HIV-exposed infants and all infants with HIV. We calculated incremental cost-effectiveness ratios with discounted (3% per year) costs and life expectancy from a health-care system perspective for all HIV-exposed infants. We judged incremental cost-effectiveness ratios of $1010 (Zimbabwe's annual gross domestic product per person) or less per year of life saved to be cost-effective. Findings When conventional assays were used for early infant diagnosis, projected undiscounted life expectancy was 22·7 years for infants with HIV and 62·5 years for all HIV-exposed infants, at a cost of $610 per HIV-exposed infant. Use of POC assays for early infant HIV diagnosis improved projected undiscounted life expectancy to 25·5 years among infants with HIV and 62·6 years among HIV-exposed infants at a cost of $690 per HIV-exposed infant. At age 12 weeks, survival among all infants with HIV was 76·1% with the conventional testing strategy and 83·5% with the POC testing strategy. The incremental cost-effectiveness ratio of POC assays versus conventional assays for early infant diagnosis was $680 per year of life saved. When conventional assay characteristics remained constant, this ratio remained under the cost-effectiveness threshold as long as the specificity and sensitivity of the POC assay were greater than 92% and 65%, respectively. Our results were robust to plausible variations in POC assay cost, the probability of ART initiation, and probability of return of the results of POC testing. Interpretation Compared with conventional assays, POC assays for early infant HIV diagnosis in Zimbabwe will improve survival, extend life expectancy, and be cost-effective for HIV-exposed infants. Funding Elizabeth Glaser Pediatric AIDS Foundation, US National Institute of Allergy and Infectious Diseases, Eunice Kennedy Shriver National Institute of Child Health and Human Development, and Unitaid.

In-person learning provides substantial benefits for K-12 school students. Risk of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection among educators, staff, students, and household members can be markedly reduced by mitigation measures including masking, ventilation, and hygiene. In addition to these measures, where community transmission is moderate to high, regular SARS-CoV-2 screening testing is recommended by recent Centers for Disease Control and Prevention (CDC) guidance for unvaccinated K-12 students and staff, and supported financially by CDC and Department of Health and Human Services initiatives. Screening can provides an added layer of risk reduction, as well as data and reassurance about in-school transmission. Financial and logistical constraints have challenged implementation of screening in public schools. We report lessons learned from a collaborative of public K-12 schools implementing and evaluating screening programs, including details of population screened, site of specimen collection, assay selection, pooled testing, and resources needed. This work supported the development of a state-wide screening program and led to dissemination of online technical resources that may support other public schools in implementing CDC guidance.

BackgroundIn 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.MethodsWe 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 measuresWe 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.ResultsAccounting 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.

Background The World Health Organization (WHO) human immunodeficiency virus (HIV) diagnostic strategy requires 6 rapid diagnostic tests (RDTs). Point-of-care nucleic acid tests (POC NATs) are costlier, less sensitive, but more specific than RDTs. Methods We simulated a 1-time screening process in Côte d’Ivoire (CI; undiagnosed prevalence: 1.8%), comparing WHO- and CI-recommended RDT-based strategies (RDT-WHO, RDT-CI) and an alternative: POC NAT to resolve RDT discordancy (NAT-Resolve). Costs included assays (RDT: $1.47; POC NAT: $27.92), antiretroviral therapy ($6–$22/month), and HIV care ($27–$38/month). We modeled 2 sensitivity/specificity scenarios: high-performing (RDT: 99.9%/99.1%; POC NAT: 95.0%/100.0%) and low-performing (RDT: 91.1%/82.9%; POC NAT: 93.3%/99.5%). Outcomes included true-positive (TP), false-positive (FP), true-negative (TN), or false-negative (FN) results; life expectancy; costs; and incremental cost-effectiveness ratios (ICERs: $/year of life saved [YLS]; threshold ≤$1720/YLS [per-capita gross domestic product]). Results Model-projected impacts of misdiagnoses were 4.4 years lost (FN vs TP; range, 3.0–13.0 years) and a $5800 lifetime cost increase (FP vs TN; range, $590–$14 680). In the high-performing scenario, misdiagnoses/10 000 000 tested were lowest for NAT-Resolve vs RDT-based strategies (FN: 409 vs 413–429; FP: 14 vs 21–28). Strategies had similar life expectancy (228 months) and lifetime costs ($220/person) among all tested; ICERs were $3450/YLS (RDT-CI vs RDT-WHO) and $120 910/YLS (NAT-Resolve vs RDT-CI). In the low-performing scenario, misdiagnoses were higher (FN: 22 845–30 357; FP: 83 724–112 702) and NAT-Resolve was cost-saving. Conclusions We projected substantial clinical and economic impacts of misdiagnoses. Using POC NAT to resolve RDT discordancy generated the fewest misdiagnoses and was not cost-effective in high-performing scenarios, but may be an important adjunct to existing RDT-based strategies in low-performing scenarios.

BackgroundData suggest that COVID-19 transmission in K-12 schools is uncommon, but few studies have confirmed this using widespread screening of asymptomatic individuals.ObjectiveTo evaluate the incidence of asymptomatic COVID-19, document the frequency of in-school transmission, and confirm feasibility of widespread asymptomatic screening in schools.DesignProspective observational studySettingSingle mid-sized suburban school district including 10 schools and a central office.ParticipantsDistrict staff and studentsInterventionsAsymptomatic screening PCR for SARS-CoV-2MeasurementsConcurrent with a hybrid model and layered mitigation, weekly pooled testing of staff and secondary students was offered using saliva samples collected at home. Identification of >1 case in a school prompted investigation for possible in-school transmission. Staff and families were surveyed about satisfaction with the screening program.ResultsFrom weeks 1-18, rates of incident COVID-19 in the surrounding community rose steadily. Weekly staff and student screening identified 0-7 asymptomatic cases/week. In week 7, 5 cases were identified among staff who shared an office setting. Enhancements to mitigation strategies were undertaken. The proportion of survey respondents self-reporting comfort with in-person learning before versus after implementation of screening increased.LimitationsBecause screening testing was not mandatory, the results from the participating population might not represent the entire school community.ConclusionsIn this school district with layered mitigation measures, in-school transmission was rare. The program identified a cluster with in-school staff-to-staff transmission and spurred enhancement of safety strategies. A weekly COVID-19 screening program can provide critical data to inform mitigation efforts, and provides school-specific, current data to inform decisions about in-person learning models. Screening provided reassurance and identified asymptomatic cases.FundingThe Wellesley Education Foundation provided funding for the testing.

The COVID-19 pandemic has induced historic disruptions in education. This agent-based network model simulated transmission in elementary and high school communities, including home, school, and interhousehold interactions., Visual Abstract. Model-Based Analysis of Safe School-Reopening Strategies. The COVID-19 pandemic has induced historic disruptions in education. This agent-based network model simulated transmission in elementary and high school communities, including home, school, and interhousehold interactions., Background: The COVID-19 pandemic has induced historic educational disruptions. In April 2021, about 40% of U.S. public school students were not offered full-time in-person education. Objective: To assess the risk for SARS-CoV-2 transmission in schools. Design: An agent-based network model was developed to simulate transmission in elementary and high school communities, including home, school, and interhousehold interactions. Setting: School structure was parametrized to reflect average U.S. classrooms, with elementary schools of 638 students and high schools of 1451 students. Daily local incidence was varied from 1 to 100 cases per 100 000 persons. Participants: Students, faculty, staff, and adult household members. Intervention: Isolation of symptomatic individuals, quarantine of an infected individual's contacts, reduced class sizes, alternative schedules, staff vaccination, and weekly asymptomatic screening. Measurements: Transmission was projected among students, staff, and families after a single infection in school and over an 8-week quarter, contingent on local incidence. Results: School transmission varies according to student age and local incidence and is substantially reduced with mitigation measures. Nevertheless, when transmission occurs, it may be difficult to detect without regular testing because of the subclinical nature of most children's infections. Teacher vaccination can reduce transmission to staff, and asymptomatic screening improves understanding of local circumstances and reduces transmission. Limitation: Uncertainty exists about the susceptibility and infectiousness of children, and precision is low regarding the effectiveness of specific countermeasures, particularly with new variants. Conclusion: With controlled community transmission and moderate mitigation, elementary schools can open safety, but high schools require more intensive mitigation. Asymptomatic screening can facilitate reopening at higher local incidence while minimizing transmission risk. Primary Funding Source: Centers for Disease Control and Prevention through the Council of State and Territorial Epidemiologists, National Institute of Allergy and Infectious Diseases, National Institute on Drug Abuse, and Facebook.

Objective: To measure mortality incidence rates and incidence rate ratios (IRR) in adolescents and youth living with perinatally acquired HIV (YPHIV) compared with those living with nonperinatally acquired HIV (YNPHIV), by region, by sex, and during the ages of 10–14, 15–19, and 20–24 years in IeDEA. Design and methods: All those with a confirmed HIV diagnosis, antiretroviral therapy (ART)-naive at enrollment, and who have post-ART follow-up while aged 10–24 years between 2004 and 2016 were included. We estimated post-ART mortality incidence rates and 95% confidence intervals (95% CI) per 100 person-years for YPHIV (enrolled into care

Background Concerns about false-negative (FN) severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) nucleic acid amplification tests (NAATs) have prompted recommendations for repeat testing if suspicion for coronavirus disease 2019 (COVID-19) infection is moderate to high. However, the frequency of FNs and patient characteristics associated with FNs are poorly understood. Methods We retrospectively reviewed test results from 15 011 adults who underwent ≥1 SARS-CoV-2 NAATs; 2699 had an initial negative NAAT and repeat testing. We defined FNs as ≥1 negative NAATs followed by a positive NAAT within 14 days during the same episode of illness. We stratified subjects with FNs by duration of symptoms before the initial FN test (≤5 days versus >5 days) and examined their clinical, radiologic, and laboratory characteristics. Results Sixty of 2699 subjects (2.2%) had a FN result during the study period. The weekly frequency of FNs among subjects with repeat testing peaked at 4.4%, coinciding with peak NAAT positivity (38%). Most subjects with FNs had symptoms (52 of 60; 87%) and chest radiography (19 of 32; 59%) consistent with COVID-19. Of the FN NAATs, 18 of 60 (30%) were performed early (ie, ≤1 day of symptom onset), and 18 of 60 (30%) were performed late (ie, >7 days after symptom onset) in disease. Among 17 subjects with 2 consecutive FNs on NP NAATs, 9 (53%) provided lower respiratory tract (LRT) specimens for testing, all of which were positive. Conclusions Our findings support repeated NAATs among symptomatic patients, particularly during periods of higher COVID-19 incidence. The LRT testing should be prioritized to increase yield among patients with high clinical suspicion for COVID-19.

Background Reports of SARS-CoV2 infection have focused on pregnant women hospitalized due to moderate to severe COVID-19 disease or asymptomatic women diagnosed through universal screening at the time of obstetric admission. Many pregnant women who have symptomatic SARS-CoV2 infection may not meet criteria for hospitalization; however, whether and how these women can be managed safely in outpatient setting is not well described. Objective We sought to describe the time to symptom and viral clearance and to identify predictors of hospitalization in order to better understand the safety of monitoring pregnant patients with symptomatic COVID-19 in the outpatient setting. Study Design We performed a retrospective cohort study of pregnant patients with symptomatic, confirmed COVID-19 illness at a large academic medical center. Patients had systematic telehealth follow up by a clinician team to assess for symptoms, provide virtual prenatal care, and arrange in-person visits when appropriate in a dedicated outpatient center. Data was collected via chart abstraction. Results Of 180 pregnant patients presenting with symptoms and undergoing RT-PCR testing, 67 patients with confirmed COVID-19 infection were identified during the study period. Nineteen (28%) required acute care given worsening of COVID-19 symptoms, and 95% of these were directed to this acute care setting due to symptom severity telehealth evaluation. Nine women (13%) were admitted to the hospital given worsening symptoms, 3 required ICU care, 2 required ventilatory support, and 2 required delivery. Women with the presenting symptoms of fever, cough, shortness of breath, chest pain, or nausea and vomiting were more likely to require admission. The median duration from initial positive test to RT-PCR viral clearance was 26 days. Disease progression, time to viral clearance and duration of symptoms did not vary significantly by trimester of infection. Conclusions Management of the majority of pregnant women with symptomatic COVID-19 illness can be accomplished in the outpatient setting with intensive and protocol-driven monitoring for symptom progression.

International audience; Introduction: Evaluating outcomes of paediatric patients with HIV provides crucial data for clinicians and policymakers. We analysed mortality and clinical events rates among children, adolescents, and youth with perinatally acquired HIV (PHIV) aged 0 to 24 years stratified by time‐varying age and CD4, before and after antiretroviral therapy (ART), in the paediatric IeDEA multiregional collaboration (East, West, Central and Southern Africa, Asia‐Pacific, and Central/South America and the Caribbean).Methods: ART‐naïve children with HIV enrolled before age 10 (proxy for perinatal infection) at IeDEA sites between 2004 and 2016, with ≥1 CD4 measurement during follow‐up were included. We estimated incidence rates (IR) and 95% confidence intervals (95% CI) of mortality and first occurrence of WHO‐4 and WHO‐3 events, excluding tuberculosis, during person‐years (PY) spent within different age (19) had increased mortality post‐ART. IRs for first occurrence of WHO‐4 and WHO‐3 events were 1.3/100 PY (95% CI: 1.2 to 1.4) and 2.1/100 PY (95% CI: 2.0 to 2.2) respectively. These were also associated with lower CD4 and younger age strata.Conclusions: Mortality and incidence of clinical events were highest in both younger (19 years) youth with PHIV. Scaling‐up services for 19 years (adolescent‐ and youth‐focused health services) is critical to improve outcomes among PHIVY.

Background We projected the clinical and economic impact of alternative testing strategies on coronavirus disease 2019 (COVID-19) incidence and mortality in Massachusetts using a microsimulation model. Methods We compared 4 testing strategies: (1) hospitalized: polymerase chain reaction (PCR) testing only for patients with severe/critical symptoms warranting hospitalization; (2) symptomatic: PCR for any COVID-19–consistent symptoms, with self-isolation if positive; (3) symptomatic + asymptomatic once: symptomatic and 1-time PCR for the entire population; and (4) symptomatic + asymptomatic monthly: symptomatic with monthly retesting for the entire population. We examined effective reproduction numbers (Re = 0.9–2.0) at which policy conclusions would change. We assumed homogeneous mixing among the Massachusetts population (excluding those residing in long-term care facilities). We used published data on disease progression and mortality, transmission, PCR sensitivity/specificity (70%/100%), and costs. Model-projected outcomes included infections, deaths, tests performed, hospital-days, and costs over 180 days, as well as incremental cost-effectiveness ratios (ICERs, $/quality-adjusted life-year [QALY]). Results At Re = 0.9, symptomatic + asymptomatic monthly vs hospitalized resulted in a 64% reduction in infections and a 46% reduction in deaths, but required >66-fold more tests/day with 5-fold higher costs. Symptomatic + asymptomatic monthly had an ICER Conclusions Testing people with any COVID-19–consistent symptoms would be cost-saving compared to testing only those whose symptoms warrant hospital care. Expanding PCR testing to asymptomatic people would decrease infections, deaths, and hospitalizations. Despite modest sensitivity, low-cost, repeat screening of the entire population could be cost-effective in all epidemic settings.

Many colleges and universities in the United States are attempting to continue undergraduate onsite learning and residential living during the COVID-19 pandemic. Modeling the outcomes, cost, and cost-effectiveness of mitigation strategies, such as social distancing, masking, and laboratory testing, can inform these efforts., Visual Abstract. COVID-19 Mitigation on College Campuses Many colleges and universities in the United States are attempting to continue undergraduate onsite learning and residential living during the COVID-19 pandemic. Modeling the outcomes, cost, and cost-effectiveness of mitigation strategies, such as social distancing, masking, and laboratory testing, can inform these efforts. Visual Abstract. COVID-19 Mitigation on College Campuses Many colleges and universities in the United States are attempting to continue undergraduate onsite learning and residential living during the COVID-19 pandemic. Modeling the outcomes, cost, and cost-effectiveness of mitigation strategies, such as social distancing, masking, and laboratory testing, can inform these efforts., Background: Colleges in the United States are determining how to operate safely amid the coronavirus disease 2019 (COVID-19) pandemic. Objective: To examine the clinical outcomes, cost, and cost-effectiveness of COVID-19 mitigation strategies on college campuses. Design: The Clinical and Economic Analysis of COVID-19 interventions (CEACOV) model, a dynamic microsimulation model, was used to examine alternative mitigation strategies. The CEACOV model tracks infections accrued by students and faculty, accounting for community transmissions. Data Sources: Data from published literature were used to obtain parameters related to COVID-19 and contact-hours. Target Population: Undergraduate students and faculty at U.S. colleges. Time Horizon: One semester (105 days). Perspective: Modified societal. Intervention: COVID-19 mitigation strategies, including social distancing, masks, and routine laboratory screening. Outcome Measures: Infections among students and faculty per 5000 students and per 1000 faculty, isolation days, tests, costs, cost per infection prevented, and cost per quality-adjusted life-year (QALY). Results of Base-Case Analysis: Among students, mitigation strategies reduced COVID-19 cases from 3746 with no mitigation to 493 with extensive social distancing and masks, and further to 151 when laboratory testing was added among asymptomatic persons every 3 days. Among faculty, these values were 164, 28, and 25 cases, respectively. Costs ranged from about $0.4 million for minimal social distancing to about $0.9 million to $2.1 million for strategies involving laboratory testing ($10 per test), depending on testing frequency. Extensive social distancing with masks cost $170 per infection prevented ($49 200 per QALY) compared with masks alone. Adding routine laboratory testing increased cost per infection prevented to between $2010 and $17 210 (cost per QALY gained, $811 400 to $2 804 600). Results of Sensitivity Analysis: Results were most sensitive to test costs. Limitation: Data are from multiple sources. Conclusion: Extensive social distancing with a mandatory mask-wearing policy can prevent most COVID-19 cases on college campuses and is very cost-effective. Routine laboratory testing would prevent 96% of infections and require low-cost tests to be economically attractive. Primary Funding Source: National Institutes of Health.

ImportanceApproximately 356,000 people stay in homeless shelters nightly in the US. These individuals are at high risk for COVID-19.ObjectiveTo assess clinical outcomes, costs, and cost-effectiveness of strategies for COVID-19 prevention and management among sheltered homeless adults.DesignWe developed a dynamic microsimulation model of COVID-19. We modeled sheltered homeless adults in Boston, Massachusetts, using cohort characteristics and costs from Boston Health Care for the Homeless Program. Disease progression, transmission, and clinical outcomes data were from published literature and national databases. We examined surging, growing, and slowing epidemics (effective reproduction numbers [Re] 2.6, 1.3, and 0.9). Costs were from a health care sector perspective; time horizon was 4 months.Setting & ParticipantsSimulated cohort of 2,258 adults residing in homeless shelters in Boston.InterventionsWe assessed combinations of daily symptom screening with same-day polymerase chain reaction (PCR) testing of screen-positive individuals, universal PCR testing every 2 weeks, hospital-based COVID-19 care, alternate care sites [ACSs] for mild/moderate COVID-19 management, and moving people from shelters to temporary housing, compared to no intervention.Main OutcomesInfections, hospital-days, costs, and cost-effectiveness.ResultsCompared to no intervention, daily symptom screening with ACSs for those with pending tests or confirmed COVID-19 and mild/moderate disease leads to 37% fewer infections and 46% lower costs when Re=2.6, 75% fewer infections and 72% lower costs when Re=1.3, and 51% fewer infections and 51% lower costs when Re=0.9. Adding universal PCR testing every 2 weeks further decreases infections in all epidemic scenarios, with incremental cost per case prevented of $1,000 (Re=2.6), $27,000 (Re=1.3), and $71,000 (Re=0.9). In all scenarios, moving shelter residents to temporary housing with universal PCR testing every 2 weeks is most effective but substantially more costly than other options. Results are most sensitive to the cost and sensitivity of PCR testing and the efficacy of ACSs in preventing transmission.Conclusions & RelevanceDaily symptom screening and ACSs for sheltered homeless adults will substantially decrease COVID-19 cases and reduce costs compared to no intervention. In a surging epidemic, adding universal PCR testing every 2 weeks further decreases cases at modest incremental cost and should be considered.Key PointsQuestionWhat are the projected clinical outcomes and costs of strategies for reducing COVID-19 infections among people experiencing sheltered homelessness?FindingsIn this microsimulation modeling study, daily symptom screening with polymerase chain reaction (PCR) testing of screen-positive individuals, paired with non-hospital care site management of people with mild to moderate COVID-19, substantially reduces infections and lowers costs over 4 months compared to no intervention, across a wide range of epidemic scenarios. In a surging epidemic, adding periodic universal PCR testing to symptom screening and non-hospital care site management improves clinical outcomes at modestly increased costs. Periodic universal PCR testing paired with temporary housing further reduces infections but at much higher cost.MeaningDaily symptom screening with PCR testing of screen-positive individuals and use of alternate care sites for COVID-19 management among sheltered homeless people will substantially prevent new cases and reduce costs compared to other strategies.

RESEARCH OBJECTIVE: Point‐of‐care (POC) assays for early infant diagnosis of HIV (EID) increase access to testing, shorten time to results, and expedite initiation of antiretroviral therapy when compared with laboratory‐based (centralized) assays. However, there is a significant gap in our understanding of its human resource impact at the facility‐level. This study evaluated the human resource labor time associated with the use of EID platforms by facility‐based health workers (HWs). STUDY DESIGN: Using time‐motion methodology, we collected direct observation and self‐reported time‐use data on EID tasks performed by HWs at health facilities in Zimbabwe. Data collection occurred at three EID facility types in Zimbabwe—five POC hubs (test samples from the hub and lower‐volume, nearby facilities), nine POC spokes (lower‐volume), and eleven facilities that use centralized laboratories. EID activities were grouped into pre‐result (counseling, administrative, blood sampling, and preparation) and total EID time (counseling to result communication). Total EID time was observed in POC hub facilities. Since EID tests were not performed on‐site at facilities using centralized laboratories and POC spoke facilities, tasks related to logging and communicating results were not observed. Instead, direct observation data were complemented with HW surveys at those facilities. Mean difference comparisons between centralized and POC EID services were performed with a two‐sample t test with allowance for unequal variances. Bootstrapping with 10 000 replicates was used to estimate the bias‐corrected and accelerated 95% confidence intervals for each measure and difference in means test. To assess whether results were robust, group comparison was performed with two‐sided permutation tests with 10 000 replicates, with same inference to those from the bootstrapped two‐sample t tests. A P‐value of

Objective: Little is known about the demographic and clinical factors associated with SARS-CoV-2 infection in pregnant women in the United States. The objective of this study was to evaluate the factors associated with SARS-CoV-2 infection in women admitted for labor and delivery, in the context of universal screening. Design: Prospective cohort study. Setting: Four Boston-area hospitals. Population: Convenience sample of all women admitted for delivery (n= 1,153). Methods: We reviewed the health records of all women admitted for delivery at the largest health system in Massachusetts between April 19-May 16, 2020. Factors evaluated for potential association with SARS-CoV-2 infection included age, BMI, race, co-morbidities, zip code, infection in a household member, number of children in the household, occupation, and insurance type. Main Outcome Measures: Risk of SARS-CoV-2 infection and associations between SARS-CoV-2 infection and clinical characteristics. Results: A total of 32 patients (2.8%, 95% confidence interval 1.9-3.9) tested positive for SARS-CoV-2 infection on admission for delivery; 24 (75.0%) of the patients who tested positive were asymptomatic. Factors associated with SARS-CoV-2 infection included: younger age, obesity, African-American or Hispanic race/ethnicity, residence in heavily affected communities, household member with known infection, essential worker occupation, and Medicaid insurance. 93.5% of patients testing positive for SARS-CoV-2 had one or more factors associated with disease acquisition. Conclusions: In this large sample of deliveries, SARS-CoV-2 infection was largely concentrated in patients with distinct demographic characteristics. Understanding factors associated with infection may inform public health efforts directed towards at risk populations and serve in counseling pregnant women.

Background Point-of-care (POC) assays for early infant diagnosis of HIV (EID) increase access to testing, shorten time to results, and expedite initiation of antiretroviral therapy when compared with laboratory-based assays. However, there is a significant gap in our understanding of its human resource impact at the facility level. This study evaluates front-line health workers' (HWs') time associated with EID. Setting Using time-motion methodology, we collected time-use data on EID tasks performed by HWs at 3 EID facility types in Zimbabwe-5 POC hubs, 9 POC spokes, and 11 facilities that used centralized laboratories. Methods Data collectors observed 30 EID processes and 30 HWs' provided self-reported time. Comparisons of mean differences of HWs' time-use between centralized and POC EID were performed with a 2-sample t test with unequal variances. Results Observed average total labor time per EID test at POC facilities was 28 minutes, 22 seconds [95% confidence interval (CI): 22:51 to 35:48], which was equivalent to the average preresult time at facilities using centralized EID. HWs performed other tasks while the machine processed samples. Observed average preresult time (counseling to sample preparation) was 18 minutes, 6 Supported by seconds (95% CI: 13:00 to 23:42) for POC compared with 27 minutes, 48 seconds (95% CI: 23:48 to 32:50) for facilities using centralized laboratories. The mean difference of 9 minutes, 42 seconds (95% CI: 03:04 to 16:18) was statistically significant. The differences in self-reported average total labor time per EID test between HWs at facilities using centralized laboratories or POC were not statistically significant. Conclusion Use of POC assays did not incur additional human resource time compared with sending dried blood spots to a centralized laboratory for EID.

Zika virus (ZIKV) is a mosquito-borne pathogen with increasing public health significance. To characterize immune responses to ZIKV, here we examine transcriptional signatures of CD4 T, CD8 T, B, and NK cells, monocytes, myeloid dendritic cells (mDCs), and plasmacytoid dendritic cells (pDCs) from three individuals with ZIKV infection. While gene expression patterns from most cell subsets display signs of impaired antiviral immune activity, pDCs from infected host have distinct transcriptional response associated with activation of innate immune recognition and type I interferon signaling pathways, but downregulation of key host factors known to support ZIKV replication steps; meanwhile, pDCs exhibit a unique expression pattern of gene modules that are correlated with alternative cell populations, suggesting collaborative interactions between pDCs and other immune cells, particularly B cells. Together, these results point towards a discrete but integrative function of pDCs in the human immune responses to ZIKV infection., Zika virus (ZIKV) poses a significant public health threat, but the immune landscape changes following ZIKV infection is still unclear. Here, the authors show, using flow cytometry and transcriptomic data, that ZIKV induces a multitude of immune responses, with plasmacytoid dendritic cells poised centrally to interact with other immune cell types.

Introduction Uptake of early infant HIV diagnosis (EID) varies widely across sub-Saharan African settings. We evaluated the potential clinical impact and cost-effectiveness of universal maternal HIV screening at infant immunization visits, with referral to EID and maternal antiretroviral therapy (ART) initiation. Methods Using the CEPAC-Pediatric model, we compared two strategies for infants born in 2017 in Cote d'Ivoire (CI), South Africa (SA), and Zimbabwe: (1) existing EID programmes offering six-week nucleic acid testing (NAT) for infants with known HIV exposure (EID), and (2) EID plus universal maternal HIV screening at six-week infant immunization visits, leading to referral for infant NAT and maternal ART initiation (screen-and-test). Model inputs included published Ivoirian/South African/Zimbabwean data: maternal HIV prevalence (4.8/30.8/16.1%), current uptake of EID (40/95/65%) and six-week immunization attendance (99/74/94%). Referral rates for infant NAT and maternal ART initiation after screen-and-test were 80%. Costs included NAT ($24/infant), maternal screening ($10/mother-infant pair), ART ($5 to 31/month) and HIV care ($15 to 190/month). Model outcomes included mother-to-child transmission of HIV (MTCT) among HIV-exposed infants, and life expectancy (LE) and mean lifetime per-person costs for children with HIV (CWH) and all children born in 2017. We calculated incremental cost-effectiveness ratios (ICERs) using discounted (3%/year) lifetime costs and LE for all children. We considered two cost-effectiveness thresholds in each country: (1) the per-capita GDP ($1720/6380/2150) per year-of-life saved (YLS), and (2) the CEPAC-generated ICER of offering 2 versus 1 lifetime ART regimens (e.g. offering second-line ART; $520/500/580/YLS). Results With EID, projected six-week MTCT was 9.3% (CI), 4.2% (SA) and 5.2% (Zimbabwe). Screen-and-test decreased total MTCT by 0.2% to 0.5%, improved LE by 2.0 to 3.5 years for CWH and 0.03 to 0.07 years for all children, and increased discounted costs by $17 to 22/child (all children). The ICER of screen-and-test compared to EID was $1340/YLS (CI), $650/YLS (SA) and $670/YLS (Zimbabwe), below the per-capita GDP but above the ICER of 2 versus 1 lifetime ART regimens in all countries. Conclusions Universal maternal HIV screening at immunization visits with referral to EID and maternal ART initiation may reduce MTCT, improve paediatric LE, and be of comparable value to current HIV-related interventions in high maternal HIV prevalence settings like SA and Zimbabwe.

Polymerase chain reaction testing at birth ("birth-testing") is suggested by new World Health Organization guidelines for rapid diagnosis of infants infected with HIV in utero. However, there are few data on the implementation of this approach in sub-Saharan Africa, and whether birth testing affects uptake of subsequent routine early infant diagnosis (EID) testing at 6-10 weeks of age is unknown.We reviewed 575 consecutive infants undergoing targeted high-risk birth testing in Cape Town, South Africa, and matched those testing HIV negative at birth (n = 551) to HIV-exposed infants who did not receive birth testing (n = 551). Maternal and infant clinical and demographic data, including EID testing uptake, were abstracted from routine records.Overall, 3.8% of all birth tests conducted were positive while later EID testing positivity rates were 0.5% for those infants testing HIV negative at birth and 0.4% for those without birth testing. Infants who underwent birth testing were less likely to present for later EID compared with those without a birth test (73% vs. 85%; P0.001). This difference persisted after adjusting for maternal and infant characteristics (adjusted odds ratio, 0.60; 95% confidence interval: 0.41-0.86) and across demographic and clinical subgroups. Infants undergoing birth testing also presented for later EID at a significantly older age (mean age, 60 vs. 50 days; P0.001).While the yield of targeted high-risk birth testing in this setting appears high, neonates testing HIV negative at birth may be less likely to present for subsequent EID testing. For birth testing implementation to contribute to overall EID program goals, structured interventions are required to support follow-up EID services after negative birth test results.

Background Cardiovascular disease (CVD) is an increasing cause of morbidity among persons living with human immunodeficiency virus (HIV; PLWH). We projected cumulative CVD risk in PLWH in care compared to the US general population and persons HIV-uninfected, but at high risk for HIV. Methods We used a mathematical model to project cumulative CVD incidence. We simulated a male and female cohort for each of 3 populations: US general population; HIV-uninfected, at high risk for HIV; and PLWH. We incorporated the higher smoking prevalence and increased CVD risk due to smoking into the HIV-infected and HIV-uninfected, at high risk for HIV populations. We incorporated HIV-attributable CVD risk, independent of smoking. Results For men, life expectancy ranged from 70.2 to 77.5 years and for women from 67.0 to 81.1 years (PLWH, US general population). Without antiretroviral therapy, lifetime CVD risk for HIV-infected males and females was 12.9% and 9.0%. For males, by age 60, cumulative CVD incidence was estimated at 20.5% in PLWH in care, 14.6% in HIV-uninfected high-risk persons, and 12.8% in the US general population. For females, cumulative CVD incidence was projected to be 13.8% in PLWH in care, 9.7% for high-risk HIV-uninfected persons, and 9.4% in the US general population. Lifetime CVD risk was 64.8% for HIV-infected males compared to 54.8% for males in the US general population, but similar among females. Conclusions CVD risks should be a part of treatment evaluation among PLWH. CVD prevention strategies could offer important health benefits for PLWH and should be evaluated.

This article seeks to report on the prevalence of asymptomatic SARS-CoV-2 in women presenting to the labor and delivery units in Boston, another high-prevalence community in the United States The 4 major hospitals affiliated with Mass General Brigham Health provide maternity care to ~14,750 women per year Over 18 days of universal testing on the labor and delivery units, 763 women were admitted and 757 (99 2%) were tested Of those, 139 had symptoms possibly consistent with COVID-19 Of symptomatic women, 11 of 139 (7 9%) tested positive Among asymptomatic women, 9 of 618 (1 5%) tested positive Thus, 9 of 20 patients positive for SARS-CoV-2 at admission (45%) had no symptoms of COVID-19 at presentation The percentage of asymptomatic women who tested positive varied by hospital: 2 7% and 1 5% in the 2 academic hospitals, 1 8% and 0 6% in the 2 community hospitals Across the 4 hospitals, none of the positive asymptomatic women developed COVID-19 symptoms during the delivery hospitalization and all 9 newborns tested negative for SARS-CoV-2 In a large healthcare system in metropolitan Boston, the study identified a low prevalence of COVID-19 infection among asymptomatic pregnant women presenting for admission to the labor and delivery units The incidence of asymptomatic infection amongst women admitted to the labor and delivery units in greater Boston was substantially lower than that of New York City despite similar case counts per capita Notably, the 1%-2% incidence of asymptomatic infection in our population more closely mirrors asymptomatic infection rates in other areas Several theories may explain the lower prevalence of asymptomatic infection in Boston compared to New York City: (1) we began testing >30 days after physical distancing orders were placed by the state and hence were sampling at a time with declining community transmission, the overall population density of greater Boston is lower than New York City, perhaps leading to less community-based transmission, and some New York hospitals transiently stopped or considered stopping birth partners from attending deliveries, which could have led to some women underreporting symptoms

BackgroundImproving maternal antiretroviral therapy (ART) retention and adherence is a critical challenge facing prevention of mother-to-child transmission (PMTCT) of HIV programs. There is an urgent need for evidence-based, cost-effective, and scalable interventions to improve maternal adherence and retention that can be feasibly implemented in overburdened health systems. Brief video-based interventions are a promising but underutilized approach to this crisis. We describe a trial protocol to evaluate the effectiveness and implementation of a standardized educational video-based intervention targeting HIV-infected pregnant women that seeks to optimize their ART retention and adherence by providing a VITAL Start (Video intervention to Inspire Treatment Adherence for Life) before committing to lifelong ART.MethodsThis study is a multisite parallel group, randomized controlled trial assessing the effectiveness of a brief facility-based video intervention to optimize retention and adherence to ART among pregnant women living with HIV in Malawi. A total of 892 pregnant women living with HIV and not yet on ART will be randomized to standard-of-care pre-ART counseling or VITAL Start. The primary outcome is a composite of retention and adherence (viral load DiscussionThis is a robust evaluation of an innovative facility-based video intervention for pregnant women living with HIV, with the potential to improve maternal and infant outcomes.Trial registrationClinicalTrials.gov,NCT03654898. Registered on 31 August 2018.

Maternal Zika virus infection was associated with increased risk of small-for-gestational-age neonates but not with preterm birth in a cohort of New York City women., OBJECTIVE: To evaluate whether antenatal Zika virus infection is associated with risk of having a small-for-gestational-age (SGA) neonate, risk of preterm birth, and lower mean birth weight of term neonates. METHODS: For this retrospective observational study, we linked birth record data for women who delivered liveborn singleton neonates in New York City in 2016 to data for pregnant women with Zika virus infection reported to the New York City Health Department. We restricted the analysis to nonsmoking, nonwhite women and adjusted for maternal characteristics. Among women with antenatal Zika virus infection, we used modified Poisson regression to assess risks of having an SGA neonate and of delivering preterm, and linear regression to assess the association of infection with mean birth weight of term neonates. RESULTS: Of 116,034 deliveries of singleton neonates in New York City in 2016, 251 (0.2%) were to women with antenatal Zika virus infection. A higher percentage of women with Zika virus infection delivered an SGA neonate compared with those without (11.2% vs 5.8%; adjusted relative risk [RR] 1.8; 95% CI 1.3–2.6). There was no difference in preterm birth prevalence for women with and without Zika virus infection (adjusted RR 1.0; 95% CI 0.69–1.6). Mean birth weight of term neonates born to women with Zika virus infection was 47 g less (95% CI −105 to 11 g); this difference was not statistically significant in crude or adjusted analyses. CONCLUSION: For a cohort of New York City women, antenatal Zika virus infection was associated with an increased risk of having an SGA neonate, but not preterm birth or lower mean birth weight of term neonates. This supports a putative association between Zika virus infection during pregnancy and SGA.

Introduction The unexpected identification of a neural tube defect (NTD) safety signal with preconception dolutegravir (DTG) exposure in the Botswana Tsepamo birth outcomes study brought into sharp focus the need for reliable data on use of new antiretrovirals in pregnancy, improved pharmacovigilance systems to evaluate safety of new drugs being introduced into populations including women of reproductive potential, and balanced risk‐benefit messaging when a safety signal is identified. Discussion The Tsepamo study NTD safety signal and accompanying regulatory responses led to uncertainty about the most appropriate approach to DTG use among women of reproductive potential, affecting global DTG roll‐out plans, and limiting DTG use in adolescent girls and women. It also revealed a tension between a public health approach to antiretroviral treatment (ART) and individual choice, and highlighted difficulties interpreting and messaging an unexpected safety signal with uncertainty about risk. This difficulty was compounded by the lack of high‐quality data on pregnancy outcomes from women receiving ART outside the Tsepamo surveillance sites and countries other than Botswana, resulting in a prolonged period of uncertainty while data on additional exposures are evaluated to refute or confirm the initial safety signal. We discuss principles for evaluating and introducing new drugs in the general population that would ensure collection of appropriate data to inform drug safety in adolescent girls and women of reproductive potential and minimize confusion about drug use in this population when a safety signal is identified. Conclusions The response to a signal suggesting a possible safety risk for a drug used in pregnancy or among women who may become pregnant needs to be rapid and comprehensive. It requires the existence of appropriately designed surveillance systems with broad population coverage; data analyses that examine risk‐benefit trade‐offs in a variety of contexts; guidance to transform this risk‐benefit balance into effective and agreed‐upon policy; involvement of the affected community and other key stakeholders; and a communication plan for all levels of knowledge and complexity. Implementation of this proposed framework for responding to safety signals is needed to ensure that any drug used in pregnancy can be rapidly and appropriately evaluated should a serious safety alert arise.

Background The NEVEREST-3 (South Africa) and MONOD-ANRS-12206 (Côte d’Ivoire, Burkina Faso) randomized trials found that switching to efavirenz (EFV) in human immunodeficiency virus–infected children >3 years old who were virologically suppressed by ritonavir-boosted lopinavir (LPV/r) was noninferior to continuing o LPV/r. We evaluated the cost-effectiveness of this strategy using the Cost-Effectiveness of Preventing AIDS Complications–Pediatric model. Methods We examined 3 strategies in South African children aged ≥3 years who were virologically suppressed by LPV/r: (1) continued LPV/r, even in case of virologic failure, without second-line regimens; continued on LPV/r with second-line option after observed virologic failure; and preemptive switch to EFV-based antiretroviral therapy (ART), with return to LPV/r after observed virologic failure. We derived data on 24-week suppression (, Using the Cost-Effectiveness of Preventing AIDS Complications–Pediatric model to project clinical outcomes, costs, and cost-effectiveness, we show that preemptively switching to efavirenz in virologically suppressed children >3 years old receiving ritonavir-boosted lopinavir (LPV/r) is cost saving compared with continued LPV/r.

Background Dolutegravir is superior to efavirenz for HIV antiretroviral therapy (ART) but may be associated with an increased risk for neural tube defects (NTDs) in newborns if used by women at conception. Objective To project clinical outcomes of ART policies for women of child-bearing potential in South Africa. Design Model of 3 strategies: efavirenz for all women of child-bearing potential (EFV), dolutegravir for all women of child-bearing potential (DTG), or World Health Organization (WHO)-recommended efavirenz without contraception or dolutegravir with contraception (WHO approach). Data sources Published data on NTD risks (efavirenz, 0.05%; dolutegravir, 0.67% [Tsepamo study]), 48-week ART efficacy with initiation (efavirenz, 60% to 91%; dolutegravir, 96%), and age-stratified fertility rates (2 to 139 per 1000 women). Target population 3.1 million South African women with HIV (aged 15 to 49 years) starting or continuing first-line ART, and their children. Time horizon 5 years. Perspective Societal. Intervention EFV, DTG, and WHO approach. Outcome measures Deaths among women and children, sexual and pediatric HIV transmissions, and NTDs. Results of base-case analysis Compared with EFV, DTG averted 13 700 women's deaths (0.44% decrease) and 57 700 sexual HIV transmissions, but increased total pediatric deaths by 4400 because of more NTDs. The WHO approach offered some benefits compared with EFV, averting 4900 women's deaths and 20 500 sexual transmissions while adding 300 pediatric deaths. Overall, combined deaths among women and children were lowest with DTG (358 000 deaths) compared with the WHO approach (362 800 deaths) or EFV (367 300 deaths). Results of sensitivity analysis Women's deaths averted with DTG exceeded pediatric deaths added with EFV unless dolutegravir-associated NTD risk was 1.5% or greater. Limitation Uncertainty in NTD risks and dolutegravir efficacy in resource-limited settings, each examined in sensitivity analyses. Conclusion Although NTD risks may be higher with dolutegravir than efavirenz, dolutegravir will lead to many fewer deaths among women, as well as fewer overall HIV transmissions. These results argue against a uniform policy of avoiding dolutegravir in women of child-bearing potential. Primary funding source National Institutes of Health, National Institute of Allergy and Infectious Diseases and Eunice Kennedy Shriver National Institute of Child Health and Human Development; Massachusetts General Hospital; and Harvard University Center for AIDS Research.

Background Diagnosis of human immunodeficiency virus (HIV) infection during early infancy (commonly known as "early infant HIV diagnosis" [EID]) followed by prompt initiation of antiretroviral therapy dramatically reduces mortality. EID testing is recommended at 6 weeks of age, but many infant infections are missed. Design/methods We simulated 4 EID testing strategies for HIV-exposed infants in South Africa: no EID (diagnosis only after illness; hereafter, "no EID"), testing once (at birth alone or at 6 weeks of age alone; hereafter, "birth alone" and "6 weeks alone," respectively), and testing twice (at birth and 6 weeks of age; hereafter "birth and 6 weeks"). We calculated incremental cost-effectiveness ratios (ICERs), using discounted costs and life expectancies for all HIV-exposed (infected and uninfected) infants. Results In the base case (guideline-concordant care), the no EID strategy produced a life expectancy of 21.1 years (in the HIV-infected group) and 61.1 years (in the HIV-exposed group); lifetime cost averaged $1430/HIV-exposed infant. The birth and 6 weeks strategy maximized life expectancy (26.5 years in the HIV-infected group and 61.4 years in the HIV-exposed group), costing $1840/infant tested. The ICER of the 6 weeks alone strategy versus the no EID strategy was $1250/year of life saved (19% of South Africa's per capita gross domestic product); the ICER for the birth and 6 weeks strategy versus the 6 weeks alone strategy was $2900/year of life saved (45% of South Africa's per capita gross domestic product). Increasing the proportion of caregivers who receive test results and the linkage of HIV-positive infants to antiretroviral therapy with the 6 weeks alone strategy improved survival more than adding a second test. Conclusions EID at birth and 6 weeks improves outcomes and is cost-effective, compared with EID at 6 weeks alone. If scale-up costs are comparable, programs should add birth testing after strengthening 6-week testing programs.

Background: Prevention of mother-to-child transmission of HIV implementation faces significant challenges globally particularly in the context of universal lifelong antiretroviral therapy (ART) for all HIV-infected pregnant women. Methods: We describe the rationale and methods of the Maternal and Child Health-Antiretroviral Therapy (MCH-ART) study an implementation science project examining strategies for providing HIV care and treatment to HIV-infected women who initiate ART during pregnancy and their HIV-exposed infants. Results: MCH-ART is composed of 3 interrelated study designs across the antenatal and postnatal periods. Phase 1 is a cross-sectional evaluation of consecutive HIV-infected pregnant women seeking antenatal care; phase 2 is an observational cohort of all women from phase 1 who are eligible for initiation of ART following local guidelines; and phase 3 is a randomized trial of strategies for delivering ART to breastfeeding women from phase 2 during the postpartum period. During each phase a set of study measurement visits is carried out separately from antenatal care and ART services; a maximum of 9 visits takes place from the beginning of antenatal care through 12 months postpartum. In parallel in-depth interviews are used to examine issues of ART adherence and retention qualitatively and costs and cost-effectiveness of models of care are examined. Separate substudies examine health outcomes in HIV-uninfected women and their HIV-unexposed infants and the role of the adherence club model for long-term adherence and retention. Discussion: Combining observational and experimental components the MCH-ART study presents a novel approach to understand and optimize ART delivery for MCH. Copyright © 2016 Wolters Kluwer Health Inc.. Open Access.

Background: The United States Centers for Disease Control and Prevention estimates that approximately 60,000 US youth are living with HIV. US youth living with HIV (YLWH) have poorer outcomes compared with adults, including lower rates of diagnosis, engagement, retention, and virologic suppression. With Adolescent Medicine Trials Network for HIV/AIDS Interventions (ATN) support, new trials of youth-centered interventions to improve retention in care and medication adherence among YLWH are underway. Objective: This study aimed to use a computer simulation model, the Cost-Effectiveness of Preventing AIDS Complications (CEPAC)-Adolescent Model, to evaluate selected ongoing and forthcoming ATN interventions to improve viral load suppression among YLWH and to define the benchmarks for uptake, effectiveness, durability of effect, and cost that will make these interventions clinically beneficial and cost-effective. Methods: This protocol, ATN 161, establishes the ATN Modeling Core. The Modeling Core leverages extensive data—already collected by successfully completed National Institutes of Health–supported studies—to develop novel approaches for modeling critical components of HIV disease and care in YLWH. As new data emerge from ongoing ATN trials during the award period about the effectiveness of novel interventions, the CEPAC-Adolescent simulation model will serve as a flexible tool to project their long-term clinical impact and cost-effectiveness. The Modeling Core will derive model input parameters and create a model structure that reflects key aspects of HIV acquisition, progression, and treatment in YLWH. The ATN Modeling Core Steering Committee, with guidance from ATN leadership and scientific experts, will select and prioritize specific model-based analyses as well as provide feedback on derivation of model input parameters and model assumptions. Project-specific teams will help frame research questions for model-based analyses as well as provide feedback regarding project-specific inputs, results, sensitivity analyses, and policy conclusions. Results: This project was funded as of September 2017. Conclusions: The ATN Modeling Core will provide critical information to guide the scale-up of ATN interventions and the translation of ATN data into policy recommendations for YLWH in the United States.