Projected Life Expectancy for Adolescents With HIV in the US.

Importance: Life expectancy is a key measure of overall population health. Life expectancy estimates for youth with HIV in the US are needed in the current HIV care and treatment context to guide health policies and resource allocation. Objective: To compare life expectancy between 18-year-old youth with perinatally acquired HIV (PHIV), youth with nonperinatally acquired HIV (NPHIV), and youth without HIV. Design, Setting, and Participants: Using a US-focused adolescent-specific Monte Carlo state-transition HIV model, we simulated individuals from age 18 years until death. We estimated probabilities of HIV treatment and care engagement, HIV progression, clinical events, and mortality from observational cohorts and clinical trials for model input parameters. The simulated individuals were 18-year-old race and ethnicity-matched youth with PHIV, youth with NPHIV, and youth without HIV; 47%, 85%, and 50% were assigned male sex at birth, respectively. Individuals were categorized by US Centers for Disease Control and Prevention-defined HIV acquisition risk: men who have sex with men, people who ever injected drugs, heterosexually active individuals at increased risk for HIV infection, or average risk for HIV infection. Distributions were 3%, 2%, 12%, and 83% for youth with PHIV and youth without HIV, and 80%, 6%, 14%, and 0% for youth with NPHIV, respectively. Among the simulated youth in this analysis, individuals were 61% Black, 24% Hispanic, and 15% White, respectively. Exposures: HIV status by timing of acquisition. Main Outcomes: Life expectancy loss for youth with PHIV and youth with NPHIV: difference between mean projected life expectancy under current and ideal HIV care scenarios compared with youth without HIV. Uncertainty intervals reflect varying adolescent HIV-related mortality inputs (95% CIs). Results: Compared with youth without HIV (life expectancy: male, 76.3 years; female, 81.7 years), male youth with PHIV and youth with NPHIV had projected life expectancy losses of 10.4 years (95% CI, 5.5-18.1) and 15.0 years (95% CI, 9.3-26.8); female youth with PHIV and youth with NPHIV had projected life expectancy losses of 11.8 years (95% CI, 6.4-20.2) and 19.5 years (95% CI, 13.8-31.6), respectively. When receiving ideal HIV care, life expectancy losses were projected to improve for youth with PHIV (male: 0.5 years [95% CI, 0.3-1.8]: female: 0.6 years [95% CI, 0.4-2.1]) but were projected to persist for youth with NPHIV (male: 6.0 years [95% CI, 5.0-9.1]; female: 10.4 years [95% CI, 9.4-13.6]). Conclusions: This adolescent-focused microsimulation modeling analysis projected that youth with HIV would have shorter life expectancy than youth without HIV. Projected differences were larger for youth with NPHIV compared with youth with PHIV. Differences in mortality by sex at birth, sexual behavior, and injection drug use contributed to lower projected life expectancy among youth with NPHIV. Interventions focused on HIV care and social factors are needed to improve life expectancy for youth with HIV in the US.

Cost-Effectiveness of Strategies for Treatment Timing for Perinatally Acquired Hepatitis C Virus.

Importance: Prevalence of chronic hepatitis C virus (HCV) infection among pregnant people is increasing in the US. HCV is transmitted vertically in 7% to 8% of births. Direct-acting antiviral (DAA) therapy was recently approved for children with HCV who are 3 years or older. The clinical and economic impacts of early DAA therapy for young children with HCV, compared with treating at older ages, are unknown. Objective: To develop a state-transition model to project clinical and economic outcomes for children with perinatally acquired HCV to investigate the cost-effectiveness of treating at various ages. Design, Setting, and Participants: The study team modeled the natural history of perinatally acquired HCV to simulate disease progression and costs of a simulated a cohort of 1000 US children with HCV from 3 years old through death. Added data were analyzed January 5, 2021, through July 1, 2022. Interventions: The study compared strategies offering 8 weeks of DAA therapy at 3, 6, 12, or 18 years old, as well as a comparator of never treating HCV. Main Outcomes and Measures: Outcomes of interest include life expectancy from 3 years and average lifetime per-person health care costs. Other clinical outcomes include cases of cirrhosis, decompensated cirrhosis, and hepatocellular carcinoma (HCC). Results: The study team projected that treating HCV at 3 years old was associated with lower mean lifetime per-person health care costs ($148 162) than deferring treatment until 6 years old ($164 292), 12 years old ($171 909), or 18 years old ($195 374). Projected life expectancy was longest when treating at 3 years old (78.36 life years [LYs]) and decreased with treatment deferral until 6 years old (76.10 LYs), 12 years old (75.99 LYs), and 18 years old (75.46 LYs). In a cohort of 1000 children with perinatally acquired HCV, treating at 3 years old prevented 89 projected cases of cirrhosis, 27 cases of HCC, and 74 liver-related deaths compared with deferring treatment until 6 years old. In sensitivity analyses, increasing loss to follow-up led to even greater clinical benefits and cost savings with earlier treatment. Conclusions and Relevance: These study results showed that DAA therapy for 3-year-old children was projected to reduce health care costs and increase survival compared with deferral until age 6 years or older. Measures to increase DAA access for young children will be important to realizing these benefits.

Projecting the Clinical and Economic Impacts of Changes to HIV Care Among Adolescents and Young Adults in the United States: Lessons From the COVID-19 Pandemic.

BACKGROUND: During the COVID-19 pandemic, many US youth with HIV (YHIV) used telehealth services; others experienced disruptions in clinic and antiretroviral therapy (ART) access. METHODS: Using the Cost-effectiveness of Preventing AIDS Complications (CEPAC)-Adolescent HIV microsimulation model, we evaluated 3 scenarios: 1) Clinic: in-person care; 2) Telehealth: virtual visits, without CD4 or viral load monitoring for 12 months, followed by return to usual care; and 3) Interruption: complete care interruption with no ART access or laboratory monitoring for 6 months (maximum clinic closure time), followed by return to usual care for 80%. We assigned higher 1-year retention (87% vs 80%) and lower cost/visit ($49 vs $56) for Telehealth vs Clinic. We modeled 2 YHIV cohorts with non-perinatal (YNPHIV) and perinatal (YPHIV) HIV, which differed by mean age (22 vs 16 years), sex at birth (85% vs 47% male), starting CD4 count (527/µL vs 635/µL), ART, mortality, and HIV-related costs. We projected life months (LMs) and costs/100 YHIV over 10 years. RESULTS: Over 10 years, LMs in Clinic and Telehealth would be similar (YNPHIV: 11 350 vs 11 360 LMs; YPHIV: 11 680 LMs for both strategies); costs would be $0.3M (YNPHIV) and $0.4M (YPHIV) more for Telehealth than Clinic. Interruption would be less effective (YNPHIV: 11 230 LMs; YPHIV: 11 620 LMs) and less costly (YNPHIV: $1.3M less; YPHIV: $0.2M less) than Clinic. Higher retention in Telehealth led to increased ART use and thus higher costs. CONCLUSIONS: Telehealth could be as effective as in-person care for some YHIV, at slightly increased cost. Short interruptions to ART and laboratory monitoring may have negative long-term clinical implications.

Daily Oral HIV Pre-exposure Prophylaxis Among Young Men Who Have Sex With Men in the United States: Cost-saving at Generic Drug Price.

BACKGROUND: Adherence and retention concerns raise questions about the effectiveness and cost-effectiveness of oral HIV pre-exposure prophylaxis (PrEP) in young men who have sex with men (YMSM). METHODS: Using an adolescent-focused simulation model, we compared annual HIV screening alone with tenofovir disoproxil fumarate/emtricitabine-based oral PrEP with every 3-month HIV screening in YMSM (aged 15-24) at increased risk of HIV. Data derived from published sources included: age-stratified HIV incidence/100 person-years (PY) on- or off-PrEP (0.6-10.1 or 0.4-6.4), PrEP retention at 6 years (28%), transmissions by HIV RNA level (0.0-78.4/100PY) and annual costs of antiretroviral therapy ($32 000-69 000), HIV care ($3100-34 600), and PrEP program/generic drug ($900/360). Outcomes included transmissions (percent of cohort infected), quality-adjusted life-years (QALYs), costs ($), and incremental cost-effectiveness ratios ($/QALY). We explored the sensitivity of findings to variation in HIV incidence and drug prices. RESULTS: Compared with annual screening alone, PrEP would increase QALYs (9.58 to 9.67), reduce new infections (37% to 30%), and decrease costs (by $5000) over 10 years. PrEP would remain cost-saving for HIV incidence off-PrEP ≥5.1/100PY or annual PrEP price ≤$1200. Over a lifetime horizon, PrEP would be cost-saving for HIV incidence off-PrEP ≥1.0/100PY, across all retention assumptions examined. PrEP would not be cost-effective at HIV incidence ≤0.1/100PY, regardless of drug price, due to programmatic costs. CONCLUSIONS: In US YMSM at increased risk of HIV, generic oral PrEP and every-3-month screening would be cost-saving compared with annual screening alone, even with high discontinuation and low adherence, over a range of HIV incidences.

Projected Life Expectancy Gains From Improvements in HIV Care in Black and White Men Who Have Sex With Men.

Importance: Substantial racial inequities exist across the HIV care continuum between non-Hispanic Black and White men who have sex with men (MSM) in the US. Objectives: To project years of life gained (YLG) with improving the HIV care continuum among Black MSM and White MSM in the US and to determine the outcomes of achieving health equity goals. Design, Setting, and Participants: The Cost-Effectiveness of Preventing AIDS Complications microsimulation model was used and populated with 2021 race-specific data to simulate HIV care among Black MSM and White MSM in the US who have acquired HIV. Analyses were completed from July 2021 to October 2023. Intervention: The study simulated status quo care using race-specific estimates: age at infection, time to diagnosis, receipt of care, and virologic suppression. The study next projected the outcomes of attaining equity-centered vs non-equity-centered goals by simulating 2 equal improvements in care goals: (10-point increased receipt of care and 5-point increased virologic suppression), 3 equity-centered goals (annual HIV testing, 95% receiving HIV care, and 95% virologic suppression) and lastly, an equitable care continuum that achieves annual HIV testing, 95% receiving care, and 95% virologic suppression in Black MSM and White MSM. One-way and multiway sensitivity and scenario analyses were conducted. Main Outcomes and Measures: Mean age at death and YLG. Results: In the simulated cohort, the mean (SD) age at HIV infection was 27.0 (10.8) years for Black MSM and 35.5 (13.6) years for White MSM. In status quo, mean age at death would be 68.8 years for Black MSM and 75.6 years for White MSM. The equal improvements in care goals would result in 0.5 YLG for Black MSM and 0.5 to 0.9 YLG for White MSM. Achieving any 1 equity-centered goal would result in 0.5 to 1.7 YLG for Black MSM and 0.4 to 1.3 YLG for White MSM. With an equitable care continuum compared with the nationally reported status quo, Black MSM and White MSM would gain 3.5 and 2.1 life-years, respectively. If the status quo HIV testing was every 6 years with 75% retained in care and 75% virologically suppressed, Black MSM would gain 4.2 life-years with an equitable care continuum. Conclusions and Relevance: In this simulation modeling study of HIV care goals, equal improvements in HIV care for Black and White MSM maintained or worsened inequities. These results suggest that equity-centered goals for the HIV care continuum are critical to mitigate long-standing inequities in HIV outcomes.

Cost-effectiveness of broadly neutralizing antibodies for infant HIV prophylaxis in settings with high HIV burdens: a simulation modeling study.

Introduction: Approximately 130 000 infants acquire HIV annually despite global maternal antiretroviral therapy scale-up. We evaluated the potential clinical impact and cost-effectiveness of offering long-acting, anti-HIV broadly neutralizing antibody (bNAb) prophylaxis to infants in three distinct settings. Methods: We simulated infants in Côte d'Ivoire, South Africa, and Zimbabwe using the Cost-Effectiveness of Preventing AIDS Complications-Pediatric (CEPAC-P) model. We modeled strategies offering a three-bNAb combination in addition to WHO-recommended standard-of-care oral prophylaxis to infants: a) with known, WHO-defined high-risk HIV exposure at birth (HR-HIVE); b) with known HIV exposure at birth (HIVE); or c) with or without known HIV exposure (ALL). Modeled infants received 1-dose, 2-doses, or Extended (every 3 months through 18 months) bNAb dosing. Base case model inputs included 70% bNAb efficacy (sensitivity analysis range: 10-100%), 3-month efficacy duration/dosing interval (1-6 months), and $20/dose cost ($5-$100/dose). Outcomes included pediatric HIV infections, life expectancy, lifetime HIV-related costs, and incremental cost-effectiveness ratios (ICERs, in US$/year-of-life-saved [YLS], assuming a ≤50% GDP per capita cost-effectiveness threshold). Results: The base case model projects that bNAb strategies targeting HIVE and ALL infants would prevent 7-26% and 10-42% additional pediatric HIV infections, respectively, compared to standard-of-care alone, ranging by dosing approach. HIVE-Extended would be cost-effective (cost-saving compared to standard-of-care) in Côte d'Ivoire and Zimbabwe; ALL-Extended would be cost-effective in South Africa (ICER: $882/YLS). BNAb strategies targeting HR-HIVE infants would result in greater lifetime costs and smaller life expectancy gains than HIVE-Extended. Throughout most bNAb efficacies and costs evaluated in sensitivity analyses, targeting HIVE infants would be cost-effective in Côte d'Ivoire and Zimbabwe, and targeting ALL infants would be cost-effective in South Africa. Discussion: Adding long-acting bNAbs to current standard-of-care prophylaxis would be cost-effective, assuming plausible efficacies and costs. The cost-effective target population would vary by setting, largely driven by maternal antenatal HIV prevalence and postpartum incidence.

Need for open data on COVID-19 vaccine uptake among pregnant people in the Caribbean: a call to action.

Pregnant people with coronavirus disease 2019 (COVID-19) have a higher risk of adverse maternal and fetal outcomes compared with pregnant people without COVID-19. In 2021, large increases in maternal mortality were reported in Jamaica, almost half of which were attributable to COVID-19. COVID-19 vaccination has been shown to reduce these risks, but low- and middle-income countries lack free, publicly available data, known as open data, on COVID-19 vaccine uptake for their pregnant populations. The objectives of this paper were to: review how high-income countries use open data to detect trends in COVID-19 vaccine uptake among pregnant people and develop vaccination distribution strategies; outline barriers to making open data available for maternal COVID-19 vaccination in the Caribbean; and propose a multipronged strategy that would increase the availability of open data on maternal COVID-19 vaccination in the Caribbean. A multipronged strategy to fill the data void would involve: (i) utilizing existing Caribbean maternal immunization data collection entities; (ii) adapting digital software tools to establish maternal electronic immunization registries; and (iii) collaborating with local partners skilled in data analytics. Making open data available for COVID-19 vaccine uptake among pregnant people in the Caribbean could offer substantial benefits, including the development of measurable maternal COVID-19 vaccination goals and the facilitation of vaccine decision-making discussions between providers and pregnant people.

Las embarazadas con la enfermedad por coronavirus del 2019 (COVID-19) tienen un mayor riesgo de resultados maternos y fetales adversos que aquellas libres de la enfermedad. En el 2021, en Jamaica se notificó un gran aumento de la mortalidad materna, del cual casi la mitad fue atribuible a la COVID-19. Se ha demostrado que la vacunación contra la COVID-19 reduce tales riesgos, pero los países de ingresos bajos y medianos carecen de datos gratuitos y de carácter público, conocidos como datos abiertos, sobre la aceptación de la vacuna contra la COVID-19 por parte de las mujeres durante el embarazo. Los objetivos del presente artículo consistieron en examinar cómo los países de ingresos altos utilizan los datos abiertos para detectar las tendencias de aceptación de la vacuna contra la COVID-19 entre las mujeres durante el embarazo y formular estrategias de distribución de las vacunas; señalar los obstáculos que dificultan la disponibilidad de los datos abiertos sobre la vacunación materna contra la COVID-19 en el Caribe; y proponer una estrategia múltiple que permita aumentar la disponibilidad de datos abiertos sobre la vacunación materna contra la COVID-19 en el Caribe. Una estrategia múltiple para llenar este vacío de información implicaría: a) utilizar las entidades de recopilación de datos sobre inmunización materna ya existentes en el Caribe; b) adaptar las herramientas informáticas digitales para crear registros electrónicos de vacunación materna; y c) colaborar con asociados locales especializados en el análisis de datos. Facilitar el acceso a los datos abiertos sobre la aceptación de la vacuna contra la COVID-19 entre las mujeres durante el embarazo en el Caribe podría ofrecer beneficios considerables, tales como el establecimiento de objetivos cuantificables en materia de vacunación materna contra la COVID-19, y propiciar las deliberaciones sobre la toma de decisiones en materia de vacunación entre los prestadores de atención de salud y las embarazadas.

Gestantes com a doença pelo coronavírus 2019 (COVID-19) têm maior risco de desfechos maternos e fetais adversos em comparação com gestantes sem COVID-19. Em 2021, foi registrado um aumento acentuado da mortalidade materna na Jamaica, e quase metade era atribuível à COVID-19. Foi demonstrado que a vacinação contra a COVID-19 reduz esses riscos, mas os países de baixa e média renda não dispõem de dados gratuitos e publicamente disponíveis (os chamados dados abertos) sobre a adesão à vacina contra a COVID-19 entre gestantes. Os objetivos deste estudo foram: analisar como os países de alta renda usam dados abertos para detectar tendências na adesão à vacina contra a COVID-19 entre gestantes e desenvolver estratégias de distribuição da vacina; descrever os obstáculos para disponibilizar dados abertos sobre a vacinação materna contra a COVID-19 no Caribe; e propor uma estratégia multifacetada que aumente a disponibilidade de dados abertos sobre a vacinação materna contra a COVID-19 no Caribe. Uma estratégia multifacetada para obter dados a fim de preencher essa lacuna envolveria: (i) utilização das entidades existentes que coletam dados de imunização materna no Caribe; (ii) adaptação de ferramentas de software para estabelecer registros eletrônicos de imunização materna; e (iii) colaboração com parceiros locais especializados em análise de dados. A disponibilização de dados abertos sobre a adesão de gestantes à vacinação contra a COVID-19 no Caribe poderia oferecer benefícios substanciais, incluindo o desenvolvimento de metas mensuráveis de vacinação materna contra a COVID-19, e facilitar discussões entre profissionais de saúde e gestantes para a tomada de decisões sobre vacinas.

Centers for AIDS Research (CFAR) Diversity, Equity, and Inclusion Pathway Initiative (CDEIPI): Developing Career Pathways for Early-Stage Scholars From Racial and Ethnic Groups Underrepresented in HIV Science and Medicine.

BACKGROUND: There is an urgent need to increase diversity among scientific investigators in the HIV research field to be more reflective of communities highly affected by the HIV epidemic. Thus, it is critical to promote the inclusion and advancement of early-stage scholars from racial and ethnic groups underrepresented in HIV science and medicine. METHODS: To widen the HIV research career pathway for early-stage scholars from underrepresented minority groups, the National Institutes of Health supported the development of the Centers for AIDS Research (CFAR) Diversity, Equity, and Inclusion Pathway Initiative (CDEIPI). This program was created through partnerships between CFARs and Historically Black Colleges and Universities and other Minority Serving Institutions throughout the United States. RESULTS: Seventeen CFARs and more than 20 Historically Black Colleges and Universities and Minority Serving Institutions have participated in this initiative to date. Programs were designed for the high school (8), undergraduate (13), post baccalaureate (2), graduate (12), and postdoctoral (4) levels. Various pedagogical approaches were used including didactic seminar series, intensive multiday workshops, summer residential programs, and mentored research internship opportunities. During the first 18 months of the initiative, 257 student scholars participated in CDEIPI programs including 150 high school, 73 undergraduate, 3 post baccalaureate, 27 graduate, and 4 postdoctoral students. CONCLUSION: Numerous student scholars from a wide range of educational levels, geographic backgrounds, and racial and ethnic minority groups have engaged in CDEIPI programs. Timely and comprehensive program evaluation data will be critical to support a long-term commitment to this unique training initiative.

Pathways and Intersections: Multifaceted Approaches to Engage Individuals From Underrepresented and Marginalized Communities in HIV Research and Career Development.

BACKGROUND: The underrepresentation of historically marginalized groups in the HIV research workforce is a barrier to reaching national Ending the Epidemic goals. SETTING: The Harvard University Center for AIDS Research (HU CFAR) Diversity Equity and Inclusion Working Group (DEI WG) uses a multifaceted approach to enhance the field's diversity. METHODS: We established a DEI WG to improve the recruitment, inclusion, and retention of underrepresented minorities (URMs) in HIV research. We use community-based, participatory processes to establish and expand education and outreach programs about HIV care and research to better connect the HU CFAR to communities affected by HIV. This article reports on the development of the WG in July 2022, progress in its first year, and future plans. RESULTS: We have built a network of >50 investigators across the university for monthly meetings; partnered with existing research pathway programs for high school, undergraduate, and graduate students, directly supporting 7 new trainees and linking CFAR investigators to additional mentorship opportunities; and created 2-year Scholar Awards for 5 URM investigators in HIV. Planned work includes needs assessments for early-stage investigators to understand factors contributing to inclusion and retention and new pathway and outreach programming being developed with community partner minority-serving institutions. CONCLUSIONS: The HU CFAR DEI WG strives to ensure that individuals from underrepresented, marginalized, and minoritized communities have an opportunity to contribute to HIV research and that research is informed by the needs of the communities affected by the epidemic. An intersectional approach should be incorporated into HIV research pathway initiatives.

Projected Benefits of Long-Acting Antiretroviral Therapy in Nonsuppressed People With Human Immunodeficiency Virus Experiencing Adherence Barriers.

Background: In a demonstration project, long-acting, injectable cabotegravir-rilpivirine (CAB-RPV) achieved viral suppression in a high proportion of people with HIV (PWH) who were virologically nonsuppressed with adherence barriers. We projected the long-term impact of CAB-RPV for nonsuppressed PWH experiencing adherence barriers. Methods: Using the Cost-Effectiveness of Preventing AIDS Complications (CEPAC) model, we compared 3 strategies: (1) standard of care oral integrase inhibitor-based ART (INSTI); (2) INSTI-based ART with supportive social services ("wraparound services" [WS]) (INSTI/WS); and (3) CAB-RPV with WS (CAB-RPV/WS). Model outcomes included viral suppression (%) and engagement in care (%) at 3 years, and life expectancy (life-years [LYs]). Base case cohort characteristics included mean age of 47y (standard deviation [SD], 10y), 90% male at birth, and baseline mean CD4 count 150/µL (SD, 75/µL). Viral suppression at 3 months was 13% (INSTI), 28% (INSTI/WS), and 60% (CAB-RPV/WS). Mean loss to follow-up was 28/100 person-years (PY) (SD, 2/100 PY) without WS and 16/100 PY (SD, 1/100 PY) with WS. Results: Projected viral suppression at 3 years would vary widely: 16% (INSTI), 38% (INSTI/WS), and 44% (CAB-RPV/WS). Life expectancy would be 7.4 LY (INSTI), 9.0 LY (INSTI/WS), and 9.4 LY (CAB-RPV/WS). Projected benefits over oral ART would be greater for PWH initiating CAB-RPV/WS at lower CD4 counts. Across plausible key parameter ranges, CAB-RPV/WS would improve viral suppression and life expectancy compared with oral INSTI strategies. Conclusions: These model-based results support that long-acting injectable CAB-RPV with extensive support services for nonsuppressed PWH experiencing adherence barriers is likely to increase viral suppression and improve survival. A prospective study to provide further evidence is needed.

Prevalence and Risk Factors for School-Associated Transmission of SARS-CoV-2.

Importance: School-associated SARS-CoV-2 transmission is described as uncommon, although the true transmission rate is unknown. Objective: To identify the SARS-CoV-2 secondary attack rate (SAR) in schools and factors associated with transmission. Design, Setting, and Participants: This cohort study examined the risk of school-based transmission of SARS-CoV-2 among kindergarten through grade 12 students and staff in 10 Massachusetts school districts during 2 periods: fall 2020/spring 2021 (F20/S21) and fall 2021 (F21). School staff collected data on SARS-CoV-2 index cases and school-based contacts, and SAR was defined as the proportion of contacts acquiring SARS-CoV-2 infection. Exposure: SARS-CoV-2. Main Outcomes and Measures: Potential factors associated with transmission, including grade level, masking, exposure location, vaccination history, and Social Vulnerability Index (SVI), were analyzed using univariable and multivariable logistic regression models. Results: For F20/S21, 8 school districts (70 schools, >33 000 students) were included and reported 435 index cases (151 staff, 216 students, and 68 missing role) with 1771 school-based contacts (278 staff, 1492 students, and 1 missing role). For F21, 5 districts (34 schools, >18 000 students) participated and reported 309 index cases (37 staff, 207 students, and 65 missing role) with 1673 school-based contacts (107 staff and 1566 students). The F20/S21 SAR was 2.2% (lower bound, 1.6%; upper bound, 26.7%), and the F21 SAR was 2.8% (lower bound, 2.6%; upper bound, 7.4%). In multivariable analysis, during F20/S21, masking was associated with a lower odds of transmission compared with not masking (odds radio [OR], 0.12; 95% CI, 0.04-0.40; P < .001). In F21, classroom exposure vs out-of-classroom exposure was associated with increased odds of transmission (OR, 2.47; 95% CI, 1.07-5.66; P = .02); a fully vaccinated vs unvaccinated contact was associated with a lower odds of transmission (OR, 0.04; 95% CI, 0.00-0.62; P < .001). In both periods, a higher SVI was associated with a greater odds of transmission. Conclusions and Relevance: In this study of Massachusetts schools, the SAR for SARS-CoV-2 among school-based contacts was low during 2 periods, and factors associated with transmission risk varied over time. These findings suggest that ongoing surveillance efforts may be essential to ensure that both targeted resources and mitigation practices remain optimal and relevant for disease prevention.

The association between all-cause mortality and HIV acquisition risk groups in the United States, 2001-2014.

OBJECTIVE: To investigate associations between all-cause mortality and human immunodeficiency virus (HIV) acquisition risk groups among people without HIV in the United States. METHODS: We used data from 23,657 (NHANES) participants (2001-2014) and the Linked Mortality File to classify individuals without known HIV into HIV acquisition risk groups: people who ever injected drugs (ever-PWID); men who have sex with men (MSM); heterosexually active people at increased risk for HIV (HIH), using low income as a proxy for increased risk. We used Cox proportional hazards models to estimate adjusted and unadjusted all-cause mortality hazard ratios (HR) with 95% confidence intervals (CI). RESULTS: Compared with sex-specific heterosexually active people at average risk for HIV (HAH), the adjusted HR (95% CI) were: male ever-PWID 1.67 (1.14, 2.46), female ever-PWID 3.50 (2.04, 6.01), MSM 1.51 (1.00, 2.27), male HIH 1.68 (1.04, 2.06), female HIH 2.35 (1.87, 2.95), and male ever-PWID 1.67 (1.14, 2.46). CONCLUSIONS: Most people at increased risk for HIV in the US experience higher all-cause mortality than people at average risk. Strategies addressing social determinants that increase HIV risk should be incorporated into HIV prevention and other health promotion programs.

A multimorbidity model for estimating health outcomes from the syndemic of injection drug use and associated infections in the United States.

BACKGROUND: Fatal drug overdoses and serious injection-related infections are rising in the US. Multiple concurrent infections in people who inject drugs (PWID) exacerbate poor health outcomes, but little is known about how the synergy among infections compounds clinical outcomes and costs. Injection drug use (IDU) converges multiple epidemics into a syndemic in the US, including opioid use and HIV. Estimated rates of new injection-related infections in the US are limited due to widely varying estimates of the number of PWID in the US, and in the absence of clinical trials and nationally representative longitudinal observational studies of PWID, simulation models provide important insights to policymakers for informed decisions. METHODS: We developed and validated a MultimorbiditY model to Reduce Infections Associated with Drug use (MYRIAD). This microsimulation model of drug use and associated infections (HIV, hepatitis C virus [HCV], and severe bacterial infections) uses inputs derived from published data to estimate national level trends in the US. We used Latin hypercube sampling to calibrate model output against published data from 2015 to 2019 for fatal opioid overdose rates. We internally validated the model for HIV and HCV incidence and bacterial infection hospitalization rates among PWID. We identified best fitting parameter sets that met pre-established goodness-of-fit targets using the Pearson's chi-square test. We externally validated the model by comparing model output to published fatal opioid overdose rates from 2020. RESULTS: Out of 100 sample parameter sets for opioid use, the model produced 3 sets with well-fitting results to key calibration targets for fatal opioid overdose rates with Pearson's chi-square test ranging from 1.56E-5 to 2.65E-5, and 2 sets that met validation targets. The model produced well-fitting results within validation targets for HIV and HCV incidence and serious bacterial infection hospitalization rates. From 2015 to 2019, the model estimated 120,000 injection-related overdose deaths, 17,000 new HIV infections, and 144,000 new HCV infections among PWID. CONCLUSIONS: This multimorbidity microsimulation model, populated with data from national surveillance data and published literature, accurately replicated fatal opioid overdose, incidence of HIV and HCV, and serious bacterial infections hospitalization rates. The MYRIAD model of IDU could be an important tool to assess clinical and economic outcomes related to IDU behavior and infections with serious morbidity and mortality for PWID.

Evaluation of "Test to Return" after COVID-19 Diagnosis in a Massachusetts Public School District.

BACKGROUND: Per Centers for Disease Control and Prevention guidance, students with COVID-19 may end isolation after 5 days if symptoms are improving; some individuals may still be contagious. Rapid antigen testing identifies possibly infectious virus. We report on a test-to-return (TTR) program in a Massachusetts school district to inform policy decisions about return to school after COVID-19. METHODS: During the 2021-2022 Omicron BA.1 surge, students with COVID-19 could return on day 6-10 if they met symptom criteria and had a negative rapid test; students with positive rapid tests and those who declined TTR remained isolated until day 11. TTR positivity rates were compared by grade level, vaccination status, symptom status, and day of infection. RESULTS: 31.4% of students had a positive TTR rapid test; there were no differences by grade or vaccination status. Ever-symptomatic students were more likely to have a positive rapid test (75/174 [43.1%] vs 18/104 [17.3%]). For ever-symptomatic students, TTR positivity decreased by day of infection. CONCLUSIONS: A substantial proportion of students may still be contagious 6 days after onset of COVID-19 infection. TTR programs may increase or reduce missed school days, depending on when return is otherwise allowed (day 6 or 11). The impact of TTR programs on school-associated transmission remains unknown.

Cost-effectiveness of point-of-care versus centralised, laboratory-based nucleic acid testing for diagnosis of HIV in infants: a systematic review of modelling studies.

BACKGROUND: Point-of-care (POC) nucleic acid testing for diagnosis of HIV in infants facilitates earlier initiation of antiretroviral therapy (ART) than with centralised (standard-of-care, SOC) testing, but can be more expensive. We evaluated cost-effectiveness data from mathematical models comparing POC with SOC to provide global policy guidance. METHODS: In this systematic review of modelling studies, we searched PubMed, MEDLINE, Embase, the National Health Service Economic Evaluation Database, Econlit, and conference abstracts, combining terms for "HIV" + "infant"/"early infant diagnosis" + "point-of-care" + "cost-effectiveness" + "mathematical models", without restrictions from database inception to July 15, 2022. We selected reports of mathematical cost-effectiveness models comparing POC with SOC for HIV diagnosis in infants younger than 18 months. Titles and abstracts were independently reviewed, with full-text review for qualifying articles. We extracted data on health and economic outcomes and incremental cost-effectiveness ratios (ICERs) for narrative synthesis. The primary outcomes of interest were ICERs (comparing POC with SOC) for ART initiation and survival of children living with HIV. FINDINGS: Our search identified 75 records through database search. 13 duplicates were excluded, leaving 62 non-duplicate articles. 57 records were excluded and five were reviewed in full text. One article was excluded as it was not a modelling study, and four qualifying studies were included in the review. These four reports were from two mathematical models from two independent modelling groups. Two reports used the Johns Hopkins model to compare POC with SOC for repeat early infant diagnosis testing in the first 6 months in sub-Saharan Africa (first report, simulation of 25 000 children) and Zambia (second report, simulation of 7500 children). In the base scenario, POC versus SOC increased probability of ART initiation within 60 days of testing from 19% to 82% (ICER per additional ART initiation range US$430-1097; 9-month cost horizon) in the first report; and from 28% to 81% in the second ($23-1609, 5-year cost horizon). Two reports compared POC with SOC for testing at 6 weeks in Zimbabwe using the Cost-Effectiveness of Preventing AIDS Complications-Paediatric model (simulation of 30 million children; lifetime horizon). POC increased life expectancy and was considered cost-effective compared with SOC (ICER $711-850 per year of life saved in HIV-exposed children). Results were robust throughout sensitivity and scenario analyses. In most scenarios, platform cost-sharing (co-use with other programmes) resulted in POC being cost-saving compared with SOC. INTERPRETATION: Four reports from two different models suggest that POC is a cost-effective and potentially cost-saving strategy for upscaling of early infant testing compared with SOC. FUNDING: Bill & Melinda Gates Foundation, Unitaid, National Institute of Allergy and Infectious Diseases, National Institute of Child Health and Human Development, WHO, and Massachusetts General Hospital Research Scholars.

Increasing the initiation of antiretroviral therapy through optimal placement of diagnostic technologies for pediatric HIV in Zimbabwe: A modeling analysis.

OBJECTIVES: Point-of-care (POC) devices for infant HIV testing provide timely result-return and increase antiretroviral (ART) initiation. We aimed to optimally locate POC devices to increase 30-day ART initiation in Matabeleland South, Zimbabwe. METHODS: We developed an optimization model to identify the locations for limited POC devices at health facilities, maximizing the number of infants who receive HIV test results and initiate ART within 30 days of testing. We compared location-optimization model results to non-model-based decision heuristics, which are more practical and less data-intensive. Heuristics assign POC devices based on demand, test positivity, laboratory result-return probability, and POC machine functionality. RESULTS: With the current placement of 11 existing POC machines, 37% of all tested infants with HIV were projected to receive results and 35% were projected to initiate ART within 30 days of testing. With optimal placement of existing machines, 46% were projected to receive results and 44% to initiate ART within 30 days, retaining three machines in current locations, moving eight to new facilities. Relocation based on the highest POC device functionality would be the best-performing heuristic decision (44% receiving results and 42% initiating ART withing 30 days); although, it still would not perform as well as the optimization-based approach. CONCLUSION: Optimal and ad hoc heuristic relocation of limited POC machines would increase timely result-return and ART initiation, without further, often costly, interventions. Location optimization can enhance decision-making regarding the placement of medical technologies for HIV care.

Cost-effectiveness of broadly neutralizing antibody prophylaxis for HIV-exposed infants in sub-Saharan African settings.

INTRODUCTION: Infant HIV prophylaxis with broadly neutralizing anti-HIV antibodies (bNAbs) could provide long-acting protection against vertical transmission. We sought to estimate the potential clinical impact and cost-effectiveness of hypothetical bNAb prophylaxis programmes for children known to be HIV exposed at birth in three sub-Saharan African settings. METHODS: We conducted a cost-effectiveness analysis using the CEPAC-Pediatric model, simulating cohorts of infants from birth through death in Côte d'Ivoire, South Africa and Zimbabwe. These settings were selected to reflect a broad range of HIV care cascade characteristics, antenatal HIV prevalence and budgetary constraints. We modelled strategies targeting bNAbs to only WHO-designated "high-risk" HIV-exposed infants (HR-HIVE) or to all HIV-exposed infants (HIVE). We compared four prophylaxis approaches within each target population: standard of care oral antiretroviral prophylaxis (SOC), and SOC plus bNAbs at birth (1-dose), at birth and 3 months (2-doses), or every 3 months throughout breastfeeding (Extended). Base-case model inputs included bNAb efficacy (60%/dose), effect duration (3 months/dose) and costs ($60/dose), based on published literature. Outcomes included paediatric HIV incidence and incremental cost-effectiveness ratios (ICERs) calculated from discounted life expectancy and lifetime HIV-related costs. RESULTS: The model projects that bNAbs would reduce absolute infant HIV incidence by 0.3-2.2% (9.6-34.9% relative reduction), varying by country, prophylaxis approach and target population. In all three settings, HR-HIVE-1-dose would be cost-saving compared to SOC. Using a 50% GDP per capita ICER threshold, HIVE-Extended would be cost-effective in all three settings with ICERs of $497/YLS in Côte d'Ivoire, $464/YLS in South Africa and $455/YLS in Zimbabwe. In all three settings, bNAb strategies would remain cost-effective at costs up to $200/dose if efficacy is ≥30%. If the bNAb effect duration were reduced to 1 month, the cost-effective strategy would become HR-HIVE-1-dose in Côte d'Ivoire and Zimbabwe and HR-HIVE-2-doses in South Africa. Findings regarding the cost-effectiveness of bNAb implementation strategies remained robust in sensitivity analyses regarding breastfeeding duration, maternal engagement in postpartum care, early infant diagnosis uptake and antiretroviral treatment costs. CONCLUSIONS: At current efficacy and cost estimates, bNAb prophylaxis for HIV-exposed children in sub-Saharan African settings would be a cost-effective intervention to reduce vertical HIV transmission.

Need for open data on COVID-19 vaccine uptake among pregnant people in the Caribbean: a call to action / Necesidad de datos abiertos sobre la aceptación de la vacuna contra la COVID-19 entre las mujeres durante el embarazo en el Caribe: un llamado a la acción / Necessidade de dados abertos sobre a adesão de gestantes à vacinação contra a COVID-19 no Caribe: um chamado à ação

ABSTRACT Pregnant people with coronavirus disease 2019 (COVID-19) have a higher risk of adverse maternal and fetal outcomes compared with pregnant people without COVID-19. In 2021, large increases in maternal mortality were reported in Jamaica, almost half of which were attributable to COVID-19. COVID-19 vaccination has been shown to reduce these risks, but low- and middle-income countries lack free, publicly available data, known as open data, on COVID-19 vaccine uptake for their pregnant populations. The objectives of this paper were to: review how high-income countries use open data to detect trends in COVID-19 vaccine uptake among pregnant people and develop vaccination distribution strategies; outline barriers to making open data available for maternal COVID-19 vaccination in the Caribbean; and propose a multipronged strategy that would increase the availability of open data on maternal COVID-19 vaccination in the Caribbean. A multipronged strategy to fill the data void would involve: (i) utilizing existing Caribbean maternal immunization data collection entities; (ii) adapting digital software tools to establish maternal electronic immunization registries; and (iii) collaborating with local partners skilled in data analytics. Making open data available for COVID-19 vaccine uptake among pregnant people in the Caribbean could offer substantial benefits, including the development of measurable maternal COVID-19 vaccination goals and the facilitation of vaccine decision-making discussions between providers and pregnant people.

RESUMEN Las embarazadas con la enfermedad por coronavirus del 2019 (COVID-19) tienen un mayor riesgo de resultados maternos y fetales adversos que aquellas libres de la enfermedad. En el 2021, en Jamaica se notificó un gran aumento de la mortalidad materna, del cual casi la mitad fue atribuible a la COVID-19. Se ha demostrado que la vacunación contra la COVID-19 reduce tales riesgos, pero los países de ingresos bajos y medianos carecen de datos gratuitos y de carácter público, conocidos como datos abiertos, sobre la aceptación de la vacuna contra la COVID-19 por parte de las mujeres durante el embarazo. Los objetivos del presente artículo consistieron en examinar cómo los países de ingresos altos utilizan los datos abiertos para detectar las tendencias de aceptación de la vacuna contra la COVID-19 entre las mujeres durante el embarazo y formular estrategias de distribución de las vacunas; señalar los obstáculos que dificultan la disponibilidad de los datos abiertos sobre la vacunación materna contra la COVID-19 en el Caribe; y proponer una estrategia múltiple que permita aumentar la disponibilidad de datos abiertos sobre la vacunación materna contra la COVID-19 en el Caribe. Una estrategia múltiple para llenar este vacío de información implicaría: a) utilizar las entidades de recopilación de datos sobre inmunización materna ya existentes en el Caribe; b) adaptar las herramientas informáticas digitales para crear registros electrónicos de vacunación materna; y c) colaborar con asociados locales especializados en el análisis de datos. Facilitar el acceso a los datos abiertos sobre la aceptación de la vacuna contra la COVID-19 entre las mujeres durante el embarazo en el Caribe podría ofrecer beneficios considerables, tales como el establecimiento de objetivos cuantificables en materia de vacunación materna contra la COVID-19, y propiciar las deliberaciones sobre la toma de decisiones en materia de vacunación entre los prestadores de atención de salud y las embarazadas.

RESUMO Gestantes com a doença pelo coronavírus 2019 (COVID-19) têm maior risco de desfechos maternos e fetais adversos em comparação com gestantes sem COVID-19. Em 2021, foi registrado um aumento acentuado da mortalidade materna na Jamaica, e quase metade era atribuível à COVID-19. Foi demonstrado que a vacinação contra a COVID-19 reduz esses riscos, mas os países de baixa e média renda não dispõem de dados gratuitos e publicamente disponíveis (os chamados dados abertos) sobre a adesão à vacina contra a COVID-19 entre gestantes. Os objetivos deste estudo foram: analisar como os países de alta renda usam dados abertos para detectar tendências na adesão à vacina contra a COVID-19 entre gestantes e desenvolver estratégias de distribuição da vacina; descrever os obstáculos para disponibilizar dados abertos sobre a vacinação materna contra a COVID-19 no Caribe; e propor uma estratégia multifacetada que aumente a disponibilidade de dados abertos sobre a vacinação materna contra a COVID-19 no Caribe. Uma estratégia multifacetada para obter dados a fim de preencher essa lacuna envolveria: (i) utilização das entidades existentes que coletam dados de imunização materna no Caribe; (ii) adaptação de ferramentas de software para estabelecer registros eletrônicos de imunização materna; e (iii) colaboração com parceiros locais especializados em análise de dados. A disponibilização de dados abertos sobre a adesão de gestantes à vacinação contra a COVID-19 no Caribe poderia oferecer benefícios substanciais, incluindo o desenvolvimento de metas mensuráveis de vacinação materna contra a COVID-19, e facilitar discussões entre profissionais de saúde e gestantes para a tomada de decisões sobre vacinas.

Prevalence of undiagnosed HIV among children in South Africa, Côte d'Ivoire and Zimbabwe: a model-based analysis to inform paediatric HIV screening programmes.

INTRODUCTION: To improve the diagnosis and survival of children living with HIV (CLWH), the World Health Organization recommends testing approaches beyond traditional infant HIV testing programmes. Information about undiagnosed HIV prevalence among children of varying ages in the general population is needed to guide innovative national/subnational case-finding and testing approaches. METHODS: We used the Cost-Effectiveness of Preventing AIDS Complications (CEPAC)-Pediatric model to estimate the prevalence of undiagnosed HIV in 2-, 5- and 10-year-old children in South Africa, Côte d'Ivoire and Zimbabwe in 2018. We simulated cohorts of children born in 2008 (10-year-olds), 2013 (5-year-olds) and 2016 (2-year-olds). Country-/year-specific inputs for pregnant/breastfeeding women included: HIV prevalence (4.2-32.3%), HIV incidence (0.03-0.24%/month), knowledge of HIV status (27-89%) and antiretroviral drug coverage (36-95%). Paediatric inputs included early infant testing coverage (6-95%) and breastfeeding duration (0-20 months). We projected the proportion of surviving CLWH in whom HIV remained undiagnosed and the undiagnosed HIV prevalence among surviving children of each age in the general population. For children born in 2016, we projected survival and diagnosis of all CLWH through 2026. We conducted sensitivity analyses on model parameters. RESULTS: In 2018, the projected proportion of surviving CLWH whose HIV remained undiagnosed in South Africa/Côte d'Ivoire/Zimbabwe was 44.2%/55.8%/52.9% among 2-year-old CLWH; 29.0%/37.8%/33.2% among 5-year-old CLWH; and 18.3%/25.4%/23.1% among 10-year-old CLWH. Projected general population undiagnosed HIV prevalence in South Africa/Côte d'Ivoire/Zimbabwe was 0.44%/0.32%/0.68% among 2-year-olds; 0.25%/0.17%/0.41% among 5-year-olds; and 0.24%/0.14%/0.38% among 10-year-olds. Among all CLWH born in 2016, 50-54% were projected to die without HIV diagnosis (and subsequently without treatment) within 10 years after birth; 80-85% of these deaths occurred in the first 2 years. CONCLUSIONS: Projected population-level undiagnosed HIV prevalence is low and sharply decreases after age 2, with more CLWH dying than being diagnosed. Despite low undiagnosed prevalence in the general population of older children, we project that a large proportion of CLWH remain undiagnosed, suggesting that innovative strategies targeting untested children of all ages outside of health facility settings should be prioritized. Programmes could consider routine testing of the general population of children below 2 in all settings and children of all ages in high-prevalence settings.

A focused multi-state model to estimate the pediatric and adolescent HIV epidemic in Thailand, 2005-2025.

BACKGROUND: We estimated the magnitude of the HIV epidemic among children and youth living with HIV (CYHIV) aged 0-25 years in Thailand, projecting forward from 2005 to 2025, and identified underreported input parameters that influence epidemic projections, in order to inform future public health and research priorities. METHODS: We developed a focused multi-state transition model incorporating perinatally-acquired HIV and non-perinatally-acquired HIV, stratified by population, including men who have sex with men (MSM), female sex workers (FSW), people who inject drugs (PWID), and the remainder of the population ("other"). We populated the model with published and programmatic data from the Thai national AIDS program when available. We projected the period from 2005-2025 and compared model results to programmatic data and projections from other models. In a scenario analysis, we projected the potential impact of pre-exposure prophylaxis (PrEP) for MSM from 2018-2025. RESULTS: The initial 2005 cohort was comprised of 66,900 CYHIV; 8% CYHIV were <5 years, 21% were 5-14 years, and 71% were 15-25 years of age. By 2020, 94% were projected to be >15 years and infections among MSM constituted 83% of all new HIV infections. The numbers of CYHIV decreased over time, projected to reach 30,760 by 2020 (-54%) and 22,640 by 2025 (-66%). The proportion of all CYHIV aged 0-25 who were diagnosed and on ART increased from 37 to 60% over the 2005-2025 period. Projections were sensitive to variations in assumptions about initial HIV prevalence and incidence among MSM, PWID, and "other" youth. CONCLUSIONS: More data on incidence rates among sexual and gender minority youth and PWID are needed to characterize the role of specific exposures and key populations in the adolescent HIV epidemic. More accurate estimates will project shifts in population and inform more targeted interventions to prevent and care for Thai CYHIV.