A Generalizable Decision-Making Framework for Selecting Onsite versus Send-out Clinical Laboratory Testing.

BACKGROUND: Laboratory networks provide services through onsite testing or through specimen transport to higher-tier laboratories. This decision is based on the interplay of testing characteristics, treatment characteristics, and epidemiological characteristics. OBJECTIVES: Our objective was to develop a generalizable model using the threshold approach to medical decision making to inform test placement decisions. METHODS: We developed a decision model to compare the incremental utility of onsite versus send-out testing for clinical purposes. We then performed Monte Carlo simulations to identify the settings under which each strategy would be preferred. Tuberculosis was modeled as an exemplar. RESULTS: The most important determinants of the decision to test onsite versus send-out were the clinical utility lost due to send-out testing delays and the accuracy decrement with onsite testing. When the sensitivity decrements of onsite testing were minimal, onsite testing tended to be preferred when send-out delays reduced clinical utility by >20%. By contrast, when onsite testing incurred large reductions in sensitivity, onsite testing tended to be preferred when utility lost due to delays was >50%. The relative cost of onsite versus send-out testing affected these thresholds, particularly when testing costs were >10% of treatment costs. CONCLUSIONS: Decision makers can select onsite versus send-out testing in an evidence-based fashion using estimates of the percentage of clinical utility lost due to send-out delays and the relative accuracy of onsite versus send-out testing. This model is designed to be generalizable to a wide variety of use cases. HIGHLIGHTS: The design of laboratory networks, including the decision to place diagnostic instruments at the point-of-care or at higher tiers as accessed through specimen transport, can be informed using the threshold approach to medical decision making.The most important determinants of the decision to test onsite versus send-out were the clinical utility lost due to send-out testing delays and the accuracy decrement with onsite testing.The threshold approach to medical decision making can be used to compare point-of-care testing accuracy decrements with the lost utility of treatment due to send-out testing delays.The relative cost of onsite versus send-out testing affected these thresholds, particularly when testing costs were >10% of treatment costs.

Forecasting the effect of HIV-targeted interventions on the age distribution of people living with HIV: a case study from Kenya.

OBJECTIVES: Expansion of ART and increases to life expectancy have led to aging among people living with HIV (PWH). DESIGN: Kenyan decisionmakers need accurate forecasts of the age distribution of PWH to inform future policies. METHODS: We developed a model of HIV in Kenya, calibrated to historical estimates of HIV epidemiology. We forecasted changes in population size and age distribution of new HIV infections and PWH under the status quo and under scale-up of HIV services. RESULTS: Without scale-up, new HIV infections were forecasted to fall from 34,000 [28,000-41,000] in 2025 to 29,000 [15,000-57,000] in 2040; the percent of new infections occurring among persons over 30 increased from 33% [20-50%] to 40% [24-62%]. The median age of PWH increased from 39 years [38-40] in 2025 to 43 years [39-46] in 2040, and the percent of PWH over age 50 increased from 26% [23-29%] to 34% [26-43%]. Under the full intervention scenario, new infections were forecasted to fall to 6,000 [3,000-12,000] in 2040. The percent of new infections occurring in people over age 30 increased to 52% [34-71%] in 2040, and there was an additional shift in the age structure of PWH (forecasted median age of 46 [43-48] and 40% [33-47%] over age 50). CONCLUSIONS: PWH in Kenya are forecasted to age over the next 15 years; improvements to the HIV care continuum are expected to contribute to the growing proportion of older PWH.

The forecasted prevalence of comorbidities and multimorbidity in people with HIV in the United States through the year 2030: A modeling study.

BACKGROUND: Estimating the medical complexity of people aging with HIV can inform clinical programs and policy to meet future healthcare needs. The objective of our study was to forecast the prevalence of comorbidities and multimorbidity among people with HIV (PWH) using antiretroviral therapy (ART) in the United States (US) through 2030. METHODS AND FINDINGS: Using the PEARL model-an agent-based simulation of PWH who have initiated ART in the US-the prevalence of anxiety, depression, stage ≥3 chronic kidney disease (CKD), dyslipidemia, diabetes, hypertension, cancer, end-stage liver disease (ESLD), myocardial infarction (MI), and multimorbidity (≥2 mental or physical comorbidities, other than HIV) were forecasted through 2030. Simulations were informed by the US CDC HIV surveillance data of new HIV diagnosis and the longitudinal North American AIDS Cohort Collaboration on Research and Design (NA-ACCORD) data on risk of comorbidities from 2009 to 2017. The simulated population represented 15 subgroups of PWH including Hispanic, non-Hispanic White (White), and non-Hispanic Black/African American (Black/AA) men who have sex with men (MSM), men and women with history of injection drug use and heterosexual men and women. Simulations were replicated for 200 runs and forecasted outcomes are presented as median values (95% uncertainty ranges are presented in the Supporting information). In 2020, PEARL forecasted a median population of 670,000 individuals receiving ART in the US, of whom 9% men and 4% women with history of injection drug use, 60% MSM, 8% heterosexual men, and 19% heterosexual women. Additionally, 44% were Black/AA, 32% White, and 23% Hispanic. Along with a gradual rise in population size of PWH receiving ART-reaching 908,000 individuals by 2030-PEARL forecasted a surge in prevalence of most comorbidities to 2030. Depression and/or anxiety was high and increased from 60% in 2020 to 64% in 2030. Hypertension decreased while dyslipidemia, diabetes, CKD, and MI increased. There was little change in prevalence of cancer and ESLD. The forecasted multimorbidity among PWH receiving ART increased from 63% in 2020 to 70% in 2030. There was heterogeneity in trends across subgroups. Among Black women with history of injection drug use in 2030 (oldest demographic subgroup with median age of 66 year), dyslipidemia, CKD, hypertension, diabetes, anxiety, and depression were most prevalent, with 92% experiencing multimorbidity. Among Black MSM in 2030 (youngest demographic subgroup with median age of 42 year), depression and CKD were highly prevalent, with 57% experiencing multimorbidity. These results are limited by the assumption that trends in new HIV diagnoses, mortality, and comorbidity risk observed in 2009 to 2017 will persist through 2030; influences occurring outside this period are not accounted for in the forecasts. CONCLUSIONS: The PEARL forecasts suggest a continued rise in comorbidity and multimorbidity prevalence to 2030, marked by heterogeneities across race/ethnicity, gender, and HIV acquisition risk subgroups. HIV clinicians must stay current on the ever-changing comorbidities-specific guidelines to provide guideline-recommended care. HIV clinical directors should ensure linkages to subspecialty care within the clinic or by referral. HIV policy decision-makers must allocate resources and support extended clinical capacity to meet the healthcare needs of people aging with HIV.

The Impact of Preventive Treatment for Multidrug- and Rifampin-Resistant Tuberculosis Exceeds Trial-Based Estimates.

BACKGROUND: Several clinical trials of tuberculosis preventive treatment (TPT) for household contacts of patients with multidrug- or rifampin-resistant tuberculosis (MDR/RR-TB) are nearing completion. The potential benefits of delivering TPT to MDR/RR-TB contacts extend beyond the outcomes that clinical trials can measure. METHODS: We developed an agent-based, household-structured TB and MDR/RR-TB transmission model, calibrated to an illustrative setting in India. We simulated contact investigation in households of patients with MDR/RR-TB, comparing an MDR/RR-TPT regimen (assuming 6-month duration, 70% efficacy) and associated active case finding against alternatives of contact investigation without TPT or no household intervention. We simulated the TB and MDR/RR-TB incidence averted relative to placebo over 2 years, as measurable by a typical trial, as well as the incidence averted over a longer time horizon, in the broader population, and relative to no contact investigation. RESULTS: Observing TPT and placebo recipients for 2 years as in a typical trial, MDR/RR-TPT was measured to prevent 72% (interquartile range, 45%-100%) of incident MDR/RR-TB among recipients; the median number needed to treat (NNT) to prevent 1 MDR/RR-TB case was 73, compared to placebo. This NNT decreased to 54 with 13-18 years of observation, to 27 when downstream transmission effects were also considered, and to 12 when the effects of active TB screening were included by comparing to a no-household-contact-intervention scenario. CONCLUSIONS: If forthcoming trial results demonstrate efficacy, the long-term population impact of TPT for MDR/RR-TB-including the large effect of increased active TB detection among MDR/RR-TB contacts-could be much greater than suggested by trial outcomes alone.

Impact of subgroup-specific heterogeneities and dynamic changes in mortality rates on forecasted population size, deaths, and age distribution of persons receiving antiretroviral treatment in the United States: a computer simulation study.

PURPOSE: Model-based forecasts of population size, deaths, and age distribution of people with HIV (PWH) are helpful for public health and clinical services planning but are influenced by subgroup-specific heterogeneities and changes in mortality rates. METHODS: Using an agent-based simulation of PWH in the United States, we examined the impact of distinct approaches to parametrizing mortality rates on forecasted epidemiology of PWH on antiretroviral treatment (ART). We first estimated mortality rates among (1) all PWH, (2) sex-specific, (3) sex-and-race/ethnicity-specific, and (4) sex-race/ethnicity-and-HIV-acquisition-risk-specific subgroups. We then assessed each scenario by (1) allowing unrestricted reductions in age-specific mortality rates over time and (2) restricting the mortality rates among PWH to subgroup-specific mortality thresholds from the general population. RESULTS: Among the eight scenarios examined, those lacking subgroup-specific heterogeneities and those allowing unrestricted reductions in future mortality rates forecasted the lowest number of deaths among all PWH and 9 of the 15 subgroups through 2030. The forecasted overall number and age distribution of people with a history of injection drug use were sensitive to inclusion of subgroup-specific mortality rates. CONCLUSIONS: Our results underscore the potential risk of underestimating future deaths by models lacking subgroup-specific heterogeneities in mortality rates, and those allowing unrestricted reductions in future mortality rates.

Evaluating Clinic-Based Interventions to Reduce Racial Differences in Mortality Among People With Human Immunodeficiency Virus in the United States.

BACKGROUND: Mortality remains elevated among Black versus White adults receiving human immunodeficiency virus (HIV) care in the United States. We evaluated the effects of hypothetical clinic-based interventions on this mortality gap. METHODS: We computed 3-year mortality under observed treatment patterns among >40 000 Black and >30 000 White adults entering HIV care in the United States from 1996 to 2019. We then used inverse probability weights to impose hypothetical interventions, including immediate treatment and guideline-based follow-up. We considered 2 scenarios: "universal" delivery of interventions to all patients and "focused" delivery of interventions to Black patients while White patients continued to follow observed treatment patterns. RESULTS: Under observed treatment patterns, 3-year mortality was 8% among White patients and 9% among Black patients, for a difference of 1 percentage point (95% confidence interval [CI], .5-1.4). The difference was reduced to 0.5% under universal immediate treatment (95% CI, -.4% to 1.3%) and to 0.2% under universal immediate treatment combined with guideline-based follow-up (95% CI, -1.0% to 1.4%). Under the focused delivery of both interventions to Black patients, the Black-White difference in 3-year mortality was -1.4% (95% CI, -2.3% to -.4%). CONCLUSIONS: Clinical interventions, particularly those focused on enhancing the care of Black patients, could have significantly reduced the mortality gap between Black and White patients entering HIV care from 1996 to 2019.

Trials underestimate the impact of preventive treatment for household contacts exposed to multidrug-resistant tuberculosis: a simulation study.

Background: Several clinical trials of tuberculosis preventive treatment (TPT) for household contacts of patients with multidrug-resistant tuberculosis (MDR-TB) are nearing completion. The potential benefits of TPT for MDR-TB contacts extend beyond the outcomes that clinical trials can measure. Methods: We developed an agent-based, household-structured TB and MDR-TB transmission model, calibrated to an illustrative setting in India, the country accounting for 26% of global MDR-TB burden. We simulated household contact investigation for contacts of patients with MDR-TB, comparing an MDR-TPT regimen against alternatives of isoniazid preventive treatment, household contact investigation without TPT, or no household contact intervention. We simulated outcomes of a clinical trial and estimated the patient-level and population-level effects over a longer time horizon. Findings: During two years of follow-up per recipient, a simulated 6-month MDR-TPT regimen with 70% efficacy against both DS- and MDR-TB infection could prevent 72% [Interquartile range (IQR): 45 - 100%] of incident MDR-TB among TPT recipients (number needed to treat (NNT) 73 [44 - 176] to prevent one MDR-TB case), compared to household contact investigation without TPT. This NNT decreased to 54 [30 - 183] when median follow-up was increased from two to 16 years, to 27 [11 - Inf] when downstream transmission effects were also considered, and to 12 [8 - 22] when these effects were compared to a scenario of no household contact intervention. Interpretation: If forthcoming trial results demonstrate efficacy, the long-term population impact of MDR-TPT implementation could be much greater than suggested by trial outcomes alone. Funding: NIH K01AI138853 and K08AI127908; Johns Hopkins Catalyst Award.

The Testing Imperative: Why the US Ending the Human Immunodeficiency Virus (HIV) Epidemic Program Needs to Renew Efforts to Expand HIV Testing in Clinical and Community-Based Settings.

Data from several modeling studies demonstrate that large-scale increases in human immunodeficiency virus (HIV) testing across settings with a high burden of HIV may produce the largest incidence reductions to support the US Ending the HIV Epidemic (EHE) initiative's goal of reducing new HIV infections 90% by 2030. Despite US Centers for Disease Control and Prevention's recommendations for routine HIV screening within clinical settings and at least yearly screening for individuals most at risk of acquiring HIV, fewer than half of US adults report ever receiving an HIV test. Furthermore, total domestic funding for HIV prevention has remained unchanged between 2013 and 2019. The authors describe the evidence supporting the value of expanded HIV testing, identify challenges in implementation, and present recommendations to address these barriers through approaches at local and federal levels to reach EHE targets.

A Growing Number of Men Who Have Sex With Men Aging With HIV (20212031): A Comparison of Two Microsimulation Models.

BACKGROUND: Men who have sex with men (MSM) on antiretroviral therapy (ART) are at risk for multimorbidity as life expectancy increases. Simulation models can project population sizes and age distributions to assist with health policy planning. METHODS: We populated the CEPAC-US model with CDC data to project the HIV epidemic among MSM in the United States. The PEARL model was predominantly informed by NA-ACCORD data (20092017). We compared projected population sizes and age distributions of MSM receiving ART (20212031) and investigated how parameters and assumptions affected results. RESULTS: We projected an aging and increasing population of MSM on ART: CEPAC-US, mean age 48.6 (SD 13.7) years in 2021 versus 53.9 (SD 15.0) years in 2031; PEARL, 46.7 (SD 13.2) years versus 49.2 (SD 14.6) years. We projected 548 800 MSM on ART (147 020 65 years) in 2031 (CEPAC-US) and 599 410 (113 400 65 years) (PEARL). Compared with PEARL, CEPAC-US projected a smaller population of MSM on ART by 2031 and a slower increase in population size, driven by higher estimates of disengagement in care and mortality. CONCLUSIONS: Findings from two structurally distinct microsimulation models suggest that the MSM population receiving ART in the United States will increase and age over the next decade. Subgroup-specific data regarding engagement in care and mortality can improve projections and inform health care policy planning.

Abuse in the Continua: HIV Prevention and Care Outcomes and Syndemic Conditions Associated with Intimate Partner Violence Among Black Gay and Bisexual Men in the Southern United States.

Intimate partner violence (IPV) has been implicated in HIV acquisition and worse HIV outcomes. Limited research focuses on the experiences of Black gay and bisexual men. Using data from cross-sectional surveys in Baltimore, Maryland, and Jackson, Mississippi, we analyzed the association between IPV victimization and HIV-related outcomes among 629 adult Black gay and bisexual men, among whom 53% self-reported a negative result at last HIV test. 40% of participants reported lifetime physical, sexual, and/or psychological IPV victimization, and 24% past-year victimization. Recent and lifetime IPV were associated with recent clinical diagnosis of STI (adjPrR: 1.44; 95%CI: 1.08-1.92) and ART medication interruptions (adjPrR: 1.59; 95%CI: 1.25-2.01), respectively. Physical IPV was inversely associated with current PrEP use (adjPrR: 0.35; 95%CI: 0.13-0.90). Recent IPV was independently correlated with depression symptomatology (adjPrR: 2.36; 95%CI: 1.61-3.47) and hazardous alcohol use (adjPrR: 1.93; 95%CI: 1.42-2.61), with evidence of interactions. IPV-HIV relationships were intersected by internalized stigma, housing instability, poverty, and lack of insurance. Tailored IPV services are urgently needed for comprehensive HIV services for Black gay and bisexual men in the U.S.

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

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

Five-Year Mortality for Adults Entering Human Immunodeficiency Virus Care Under Universal Early Treatment Compared With the General US Population.

BACKGROUND: Mortality among adults with human immunodeficiency virus (HIV) remains elevated over those in the US general population, even in the years after entry into HIV care. We explore whether the elevation in 5-year mortality would have persisted if all adults with HIV had initiated antiretroviral therapy within 3 months of entering care. METHODS: Among 82 766 adults entering HIV care at North American AIDS Cohort Collaboration clinical sites in the United States, we computed mortality over 5 years since entry into HIV care under observed treatment patterns. We then used inverse probability weights to estimate mortality under universal early treatment. To compare mortality with those for similar individuals in the general population, we used National Center for Health Statistics data to construct a cohort representing the subset of the US population matched to study participants on key characteristics. RESULTS: For the entire study period (1999-2017), the 5-year mortality among adults with HIV was 7.9% (95% confidence interval [CI]: 7.6%-8.2%) higher than expected based on the US general population. Under universal early treatment, the elevation in mortality for people with HIV would have been 7.2% (95% CI: 5.8%-8.6%). In the most recent calendar period examined (2011-2017), the elevation in mortality for people with HIV was 2.6% (95% CI: 2.0%-3.3%) under observed treatment patterns and 2.1% (.0%-4.2%) under universal early treatment. CONCLUSIONS: Expanding early treatment may modestly reduce, but not eliminate, the elevation in mortality for people with HIV.

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

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

Projecting the age-distribution of men who have sex with men receiving HIV treatment in the United States.

BACKGROUND: The age-distribution of men who have sex with men (MSM) continues to change in the 'Treat-All' era as effective test-and-treat programs target key-populations. However, the nature of these changes and potential racial heterogeneities remain uncertain. METHODS: The PEARL model is an agent-based simulation of MSM in HIV care in the US, calibrated to data from the North American AIDS Cohort Collaboration on Research and Design (NA-ACCORD). RESULTS: PEARL projects a gradual decrease in median age of MSM at ART initiation from 36 to 31 years during 2010-2030, accompanied by changes in mortality among Black, White, and Hispanic MSM on ART by -8.4%, 42.4% and -19.6%. The median age of all MSM on ART is projected to increase from 45 to 47 years from 2010-2030, with the proportion of ART-users age ≥60y increasing from 6.7% to 28.0%. Almost half (49.7%) of White MSM ART-users are projected to age ≥60y by 2030, compared to 19.5% of Black and 17.2% of Hispanic MSM. CONCLUSIONS: The overall age of US MSM in HIV care is expected to increase over the next decade, and differentially by race/ethnicity. As this population age, HIV programs should expand care for age-related causes of morbidity and mortality.

The shifting age distribution of people with HIV using antiretroviral therapy in the United States.

OBJECTIVE: To project the future age distribution of people with HIV using antiretroviral therapy (ART) in the United States, under expected trends in HIV diagnosis and survival (baseline scenario) and achieving the ending the HIV epidemic (EHE) goals of a 75% reduction in HIV diagnoses from 2020 to 2025 and sustaining levels to 2030 (EHE75% scenario). DESIGN: An agent-based simulation model with mathematical functions estimated from North American AIDS Cohort Collaboration on Research and Design data and parameters from the US Centers for Disease Control and Prevention's annual HIV surveillance reports. METHODS: The PEARL (ProjEcting Age, MultimoRbidity, and PoLypharmacy in adults with HIV) model simulated individuals in 15 subgroups of sex-and-HIV acquisition risk and race/ethnicity. Simulation outcomes from the baseline scenario are compared with outcomes from the EHE75% scenario. RESULTS: Under the baseline scenario, PEARL projects a substantial increase in number of ART-users over time, reaching a population of 909 638 [95% uncertainty range (UR): 878 449-946 513] by 2030. The overall median age increased from 50 years in 2020 to 52 years in 2030, with 23% of ART-users age ≥65 years in 2030. Under the EHE75% scenario, the projected number of ART-users was 718 348 [703 044-737 817] (median age = 56 years) in 2030, with a 70% relative reduction in ART-users <30 years and a 4% relative reduction in ART-users age ≥65 years compared to baseline, and persistent heterogeneities in projected numbers by sex-and-HIV acquisition risk group and race/ethnicity. CONCLUSIONS: It is critical to prepare healthcare systems to meet the impending demand of the US population aging with HIV.

Achieving a "step change" in the tuberculosis epidemic through comprehensive community-wide intervention: a model-based analysis.

BACKGROUND: Global progress towards reducing tuberculosis (TB) incidence and mortality has consistently lagged behind the World Health Organization targets leading to a perception that large reductions in TB burden cannot be achieved. However, several recent and historical trials suggest that intervention efforts that are comprehensive and intensive can have a substantial epidemiological impact. We aimed to quantify the potential epidemiological impact of an intensive but realistic, community-wide campaign utilizing existing tools and designed to achieve a "step change" in the TB burden. METHODS: We developed a compartmental model that resembled TB transmission and epidemiology of a mid-sized city in India, the country with the greatest absolute TB burden worldwide. We modeled the impact of a one-time, community-wide screening campaign, with treatment for TB disease and preventive therapy for latent TB infection (LTBI). This one-time intervention was followed by the strengthening of the tuberculosis-related health system, potentially facilitated by leveraging the one-time campaign. We estimated the tuberculosis cases and deaths that could be averted over 10 years using this comprehensive approach and assessed the contributions of individual components of the intervention. RESULTS: A campaign that successfully screened 70% of the adult population for active and latent tuberculosis and subsequently reduced diagnostic and treatment delays and unsuccessful treatment outcomes by 50% was projected to avert 7800 (95% range 5450-10,200) cases and 1710 (1290-2180) tuberculosis-related deaths per 1 million population over 10 years. Of the total averted deaths, 33.5% (28.2-38.3) were attributable to the inclusion of preventive therapy and 52.9% (48.4-56.9) to health system strengthening. CONCLUSIONS: A one-time, community-wide mass campaign, comprehensively designed to detect, treat, and prevent tuberculosis with currently existing tools can have a meaningful and long-lasting epidemiological impact. Successful treatment of LTBI is critical to achieving this result. Health system strengthening is essential to any effort to transform the TB response.

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

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

Integrated screening and treatment services for HIV, hypertension and diabetes in Kenya: assessing the epidemiological impact and cost-effectiveness from a national and regional perspective.

INTRODUCTION: As people with HIV age, prevention and management of other communicable and non-communicable diseases (NCDs) will become increasingly important. Integration of screening and treatment for HIV and NCDs is a promising approach for addressing the dual burden of these diseases. The aim of this study was to assess the epidemiological impact and cost-effectiveness of a community-wide integrated programme for screening and treatment of HIV, hypertension and diabetes in Kenya. METHODS: Coupling a microsimulation of cardiovascular diseases (CVDs) with a population-based model of HIV dynamics (the Spectrum), we created a hybrid HIV/CVD model. Interventions were modelled from year 2019 (baseline) to 2023, and population was followed to 2033. Analyses were carried at a national level and for three selected regions (Nairobi, Coast and Central). RESULTS: At a national level, the model projected 7.62 million individuals living with untreated hypertension, 692,000 with untreated diabetes and 592,000 individuals in need of ART in year 2018. Improving ART coverage from 68% at baseline to 88% in 2033 reduced HIV incidence by an estimated 64%. Providing NCD treatment to 50% of diagnosed cases from 2019 to 2023 and maintaining them on treatment afterwards could avert 116,000 CVD events and 43,600 CVD deaths in Kenya over the next 15 years. At a regional level, the estimated impact of expanded HIV services was highest in Nairobi region (averting 42,100 HIV infections compared to baseline) while Central region experienced the highest impact of expanded NCD treatment (with a reduction of 22,200 CVD events). The integrated HIV/NCD intervention could avert 7.76 million disability-adjusted-life-years (DALYs) over 15 years at an estimated cost of $6.68 billion ($445.27 million per year), or $860.30 per DALY averted. At a cost-effectiveness threshold of $2,010 per DALY averted, the probability of cost-effectiveness was 0.92, ranging from 0.71 in Central to 0.92 in Nairobi region. CONCLUSIONS: Integrated screening and treatment of HIV and NCDs can be a cost-effective and impactful approach to save lives of people with HIV in Kenya, although important variation exists at the regional level. Containing the substantial costs required for scale-up will be critical for management of HIV and NCDs on a national scale.

Informing decision-making for universal access to quality tuberculosis diagnosis in India: an economic-epidemiological model.

BACKGROUND: India and many other high-burden countries have committed to providing universal access to high-quality diagnosis and drug susceptibility testing (DST) for tuberculosis (TB), but the most cost-effective approach to achieve this goal remains uncertain. Centralized testing at district-level hub facilities with a supporting sample transport network can generate economies of scale, but decentralization to the peripheral level may provide faster diagnosis and reduce losses to follow-up (LTFU). METHODS: We generated functions to evaluate the costs of centralized and decentralized molecular testing for tuberculosis with Xpert MTB/RIF (Xpert), a WHO-endorsed test which can be performed at centralized and decentralized levels. We merged the cost estimates with an agent-based simulation of TB transmission in a hypothetical representative region in India to assess the impact and cost-effectiveness of each strategy. RESULTS: Compared against centralized Xpert testing, decentralization was most favorable when testing volume at decentralized facilities and pre-treatment LTFU were high, and specimen transport network was exclusively established for TB. Assuming equal quality of centralized and decentralized testing, decentralization was cost-saving, saving a median $338,000 (interquartile simulation range [IQR] - $222,000; $889,000) per 20 million people over 10 years, in the most cost-favorable scenario. In the most cost-unfavorable scenario, decentralized testing would cost a median $3161 [IQR $2412; $4731] per disability-adjusted life year averted relative to centralized testing. CONCLUSIONS: Decentralization of Xpert testing is likely to be cost-saving or cost-effective in most settings to which these simulation results might generalize. More decentralized testing is more cost-effective in settings with moderate-to-high peripheral testing volumes, high existing clinical LTFU, inability to share specimen transport costs with other disease entities, and ability to ensure high-quality peripheral Xpert testing. Decision-makers should assess these factors when deciding whether to decentralize molecular testing for tuberculosis.

Gonorrhoea and chlamydia diagnosis as an entry point for HIV pre-exposure prophylaxis: a modelling study.

OBJECTIVES: Neisseria gonorrhoeae (NG) and Chlamydia trachomatis (CT) increase the risk of HIV transmission among men who have sex with men (MSM). Diagnosis of NG/CT may provide an efficient entry point for prevention of HIV through the delivery of pre-exposure prophylaxis (PrEP); however, the additional population-level impact of targeting PrEP to MSM diagnosed with NG/CT is unknown. DESIGN: An agent-based simulation model of NG/CT and HIV cocirculation among MSM calibrated against census data, disease surveillance reports and the US National HIV Behavioral Surveillance study. SETTING: Baltimore City, Maryland, USA. INTERVENTIONS: PrEP implementation was modelled under three alternative scenarios: (1) PrEP delivery at NG/CT diagnosis (targeted delivery), (2) PrEP evaluation at NG/CT screening/testing and (3) PrEP evaluation in the general community (untargeted). MAIN OUTCOME: The projected incidence of HIV after 20 years of PrEP delivery under two alternatives: when equal numbers of MSM are (1) screened for PrEP or (2) receive PrEP in each year. RESULTS: Assuming 60% uptake and 60% adherence, targeting PrEP to MSM diagnosed with NG/CT could reduce HIV incidence among MSM in Baltimore City by 12.4% (95% uncertainty range (UR) 10.3% to 14.4%) in 20 years, relative to no PrEP. Expanding the coverage of NG/CT screening (such that individuals experience a 50% annual probability of NG/CT screening and evaluation for PrEP on NG/CT diagnosis) can further increase the impact of targeted PrEP to generate a 22.0% (95% UR 20.1% to 23.9%) reduction in HIV incidence within 20 years. When compared with alternative implementation scenarios, PrEP evaluation at NG/CT diagnosis increased impact of PrEP on HIV incidence by 1.5(95% UR 1.1 to 1.9) times relative to a scenario in which PrEP evaluation happened at the time of NG/CT screening/testing and by 1.6 (95% UR 1.2 to 2.2) times relative to evaluating random MSM from the community. CONCLUSIONS: Targeting MSM infected with NG/CT increases the efficiency and effectiveness of PrEP delivery. If high levels of sexually transmitted infection screening can be achieved at the community level, NG/CT diagnosis may be a highly effective entry point for PrEP initialisation.