Improving HIV preexposure prophylaxis uptake with artificial intelligence and automation: a systematic review.

OBJECTIVES: To identify studies promoting the use of artificial intelligence (AI) or automation with HIV preexposure prophylaxis (PrEP) care and explore ways for AI to be used in PrEP interventions. DESIGN: Systematic review. METHODS: We searched in the US Centers for Disease Control and Prevention Research Synthesis database through November 2023; PROSPERO (CRD42023458870). We included studies published in English that reported using AI or automation in PrEP interventions. Two reviewers independently reviewed the full text and extracted data by using standard forms. Risk of bias was assessed using either the revised Cochrane risk-of-bias tool for randomized trials for randomized controlled trials or an adapted Newcastle-Ottawa Quality Assessment Scale for nonrandomized studies. RESULTS: Our search identified 12 intervention studies (i.e., interventions that used AI/automation to improve PrEP care). Currently available intervention studies showed AI/automation interventions were acceptable and feasible in PrEP care while improving PrEP-related outcomes (i.e., knowledge, uptake, adherence, discussion with care providers). These interventions have used AI/automation to reduce workload (e.g., directly observed therapy) and helped non-HIV specialists prescribe PrEP with AI-generated clinical decision-support. Automated tools can also be developed with limited budget and staff experience. CONCLUSIONS: AI and automation have high potential to improve PrEP care. Despite limitations of included studies (e.g., the small sample sizes and lack of rigorous study design), our review suggests that by using aspects of AI and automation appropriately and wisely, these technologies may accelerate PrEP use and reduce HIV infection.

Simulation of Full HIV Cluster Networks in a Nationally Representative Model Indicates Intervention Opportunities.

BACKGROUND: Clusters of rapid HIV transmission in the United States are increasingly recognized through analysis of HIV molecular sequence data reported to the National HIV Surveillance System. Understanding the full extent of cluster networks is important to assess intervention opportunities. However, full cluster networks include undiagnosed and other infections that cannot be systematically observed in real life. METHODS: We replicated HIV molecular cluster networks during 2015-2017 in the United States using a stochastic dynamic network simulation model of sexual transmission of HIV. Clusters were defined at the 0.5% genetic distance threshold. Ongoing priority clusters had growth of ≥3 diagnoses/year in multiple years; new priority clusters first had ≥3 diagnoses/year in 2017. We assessed the full extent, composition, and transmission rates of new and ongoing priority clusters. RESULTS: Full clusters were 3-9 times larger than detected clusters, with median detected cluster sizes in new and ongoing priority clusters of 4 (range 3-9) and 11 (range 3-33), respectively, corresponding to full cluster sizes with a median of 14 (3-74) and 94 (7-318), respectively. A median of 36.3% (range 11.1%-72.6%) of infections in the full new priority clusters were undiagnosed. HIV transmission rates in these clusters were >4 times the overall rate observed in the entire simulation. CONCLUSIONS: Priority clusters reflect networks with rapid HIV transmission. The substantially larger full extent of these clusters, high proportion of undiagnosed infections, and high transmission rates indicate opportunities for public health intervention and impact.

Assessing the Impact of COVID-19 on HIV Outcomes in the United States: A Modeling Study.

BACKGROUND: The COVID-19 pandemic impacted sexual behaviors and the HIV continuum of care in the United States, reducing HIV testing and diagnosis, and use of preexposure prophylaxis and antiretroviral therapy. We aimed to understand the future implications of these effects through a modeling study. METHODS: We first ran our compartmental model of HIV transmission in the United States accounting for pandemic-related short-term changes in transmission behavior and HIV prevention and care provision in 2020 to 2021 only. We then ran a comparison scenario that did not apply pandemic effects but assumed a continuation of past HIV prevention and care trends. We compared results from the 2 scenarios through 2024. RESULTS: HIV incidence was 4·4% lower in 2020 to 2021 for the pandemic scenario compared with the no-pandemic scenario because of reduced levels of transmission behavior, despite reductions in HIV prevention and care caused by the pandemic. However, reduced care led to less viral load suppression among people with HIV in 2020, and in turn, our model resulted in a slightly greater incidence of 2·0% from 2022 to 2024 in the COVID-19 scenario, as compared with the non-COVID scenario. DISCUSSION: Disruptions in HIV prevention and care services during COVID-19 may lead to somewhat higher postpandemic HIV incidence than assuming prepandemic trends in HIV care and prevention continued. These results underscore the importance of continuing to increase HIV prevention and care efforts in the coming years.

COVID-19-related excess missed HIV diagnoses in the United States in 2021.

OBJECTIVE: Coronavirus disease 2019 (COVID-19) and related disruptions led to a significant decline in HIV diagnoses in the United States in 2020. A previous analysis estimated 18% fewer diagnoses than expected among persons with HIV (PWH) acquiring infection in 2019 or earlier, suggesting that the decline in overall diagnoses cannot be attributed solely to decreased transmission. This analysis evaluates the progress made towards closing the 2020 diagnosis deficit in 2021. METHODS: We apply previously developed methods analyzing 2021 diagnosis data from the National HIV Surveillance System to determine whether 2021 diagnosis levels of PWH infected pre-2020 are above or below the expected pre-COVID trends. Results are stratified by assigned sex at birth, transmission group, geographic region, and race/ethnicity. RESULTS: In 2021, HIV diagnoses returned to pre-COVID levels among all PWH acquiring infection 2011-2019. Among Hispanic/Latino PWH and male individuals, diagnoses returned to pre-COVID levels. White PWH, MSM, and PWH living in the south and northeast showed higher-than-expected levels of diagnosis in 2021. For the remaining populations, there were fewer HIV diagnoses in 2021 than expected. CONCLUSION: Although overall diagnoses among persons acquiring HIV pre-2020 returned to pre-COVID levels, the diagnosis gap observed in 2020 remained unclosed at the end of 2021. Fewer than expected diagnoses among certain populations indicate that COVID-19-related disruptions to HIV diagnosis trends remained in 2021. Although some groups showed higher-than-expected levels of diagnoses, such increases were smaller than corresponding 2020 decreases. Expanded testing programs designed to close these gaps are essential.

Mortality Among Persons With HIV in the United States During the COVID-19 Pandemic: A Population-Level Analysis.

BACKGROUND: Whether the COVID-19 pandemic has had a disproportionate impact on mortality among persons with diagnosed HIV (PWDH) in the United States is unclear. Through our macroscale analysis, we seek to better understand how the COVID-19 pandemic affected mortality among PWDH. METHODS: We obtained mortality and population data for the years 2018-2020 from the National HIV Surveillance System for the US PWDH population and from publicly available data for the general population. We computed mortality rates and excess mortality for both the general and PWDH populations. Stratifications by age, race/ethnicity, and sex were considered. For each group, we determined whether the 2020 mortality rates and mortality risk ratio showed a statistically significant change from 2018 to 2019. RESULTS: Approximately 1550 excess deaths occurred among PWDH in 2020, with Black, Hispanic/Latino, and PWDH aged 55 years and older comprising the majority of excess deaths. Mortality rates increased in 2020 from 2018-2019 across the general population in all groups. Among PWDH, mortality rates either increased or showed no statistically significant change. These increases were similar to, or smaller than, those observed in the general population, resulting in a 7.7% decrease in the mortality risk ratio between PWDH and the general population. CONCLUSIONS: While mortality rates among PWDH increased in 2020 relative to 2018-2019, the increases were smaller, or of similar magnitude, to those observed in the general population. We thus do not find evidence of elevated mortality risk from the COVID-19 pandemic among PWDH. These findings held across subpopulations stratified by age, sex, and racial/ethnic group.

Isolating the Effect of COVID-19-Related Disruptions on HIV Diagnoses in the United States in 2020.

BACKGROUND: Diagnoses of HIV in the United States decreased by 17% in 2020 due to COVID-related disruptions. The extent to which this decrease is attributable to changes in HIV testing versus HIV transmission is unclear. We seek to better understand this issue by analyzing the discrepancy in expected versus observed HIV diagnoses in 2020 among persons who acquired HIV between 2010 and 2019 because changes in diagnosis patterns in this cohort cannot be attributed to changes in transmission. METHODS: We developed 3 methods based on the CD4-depletion model to estimate excess missed diagnoses in 2020 among persons with HIV (PWH) infected from 2010 to 2019. We stratified the results by transmission group, sex assigned at birth, race/ethnicity, and region to examine differences by group and confirm the reliability of our estimates. We performed similar analyses projecting diagnoses in 2019 among PWH infected from 2010 to 2018 to evaluate the accuracy of our methods against surveillance data. RESULTS: There were approximately 3100-3300 (approximately 18%) fewer diagnoses than expected in 2020 among PWH infected from 2010 to 2019. Females (at birth), heterosexuals, persons who inject drugs, and Hispanic/Latino PWH missed diagnoses at higher levels than the overall population. Validation and stratification analyses confirmed the accuracy and reliability of our estimates. CONCLUSIONS: The substantial drop in number of previously infected PWH diagnosed in 2020 suggests that changes in testing played a substantial role in the observed decrease. Levels of missed diagnoses differed substantially across population subgroups. Increasing testing efforts and innovative strategies to reach undiagnosed PWH are needed to offset this diagnosis gap. These analyses may be used to inform future estimates of HIV transmission during the COVID-19 pandemic.

Modeling nonlocal behavior in epidemics via a reaction-diffusion system incorporating population movement along a network.

The outbreak of COVID-19, beginning in 2019 and continuing through the time of writing, has led to renewed interest in the mathematical modeling of infectious disease. Recent works have focused on partial differential equation (PDE) models, particularly reaction-diffusion models, able to describe the progression of an epidemic in both space and time. These studies have shown generally promising results in describing and predicting COVID-19 progression. However, people often travel long distances in short periods of time, leading to nonlocal transmission of the disease. Such contagion dynamics are not well-represented by diffusion alone. In contrast, ordinary differential equation (ODE) models may easily account for this behavior by considering disparate regions as nodes in a network, with the edges defining nonlocal transmission. In this work, we attempt to combine these modeling paradigms via the introduction of a network structure within a reaction-diffusion PDE system. This is achieved through the definition of a population-transfer operator, which couples disjoint and potentially distant geographic regions, facilitating nonlocal population movement between them. We provide analytical results demonstrating that this operator does not disrupt the physical consistency or mathematical well-posedness of the system, and verify these results through numerical experiments. We then use this technique to simulate the COVID-19 epidemic in the Brazilian region of Rio de Janeiro, showcasing its ability to capture important nonlocal behaviors, while maintaining the advantages of a reaction-diffusion model for describing local dynamics.

Data-Driven Simulation of Fisher-Kolmogorov Tumor Growth Models Using Dynamic Mode Decomposition.

The computer simulation of organ-scale biomechanistic models of cancer personalized via routinely collected clinical and imaging data enables to obtain patient-specific predictions of tumor growth and treatment response over the anatomy of the patient's affected organ. These patient-specific computational forecasts have been regarded as a promising approach to personalize the clinical management of cancer and derive optimal treatment plans for individual patients, which constitute timely and critical needs in clinical oncology. However, the computer simulation of the underlying spatiotemporal models can entail a prohibitive computational cost, which constitutes a barrier to the successful development of clinically-actionable computational technologies for personalized tumor forecasting. To address this issue, here we propose to utilize dynamic-mode decomposition (DMD) to construct a low-dimensional representation of cancer models and accelerate their simulation. DMD is an unsupervised machine learning method based on the singular value decomposition that has proven useful in many applications as both a predictive and a diagnostic tool. We show that DMD may be applied to Fisher-Kolmogorov models, which constitute an established formulation to represent untreated solid tumor growth that can further accommodate other relevant cancer phenomena (e.g., therapeutic effects, mechanical deformation). Our results show that a DMD implementation of this model over a clinically relevant parameter space can yield promising predictions, with short to medium-term errors remaining under 1% and long-term errors remaining under 20%, despite very short training periods. In particular, we have found that, for moderate to high tumor cell diffusivity and low to moderate tumor cell proliferation rate, DMD reconstructions provide accurate, bounded-error reconstructions for all tested training periods. Additionally, we also show that the three-dimensional DMD reconstruction of the tumor field can be leveraged to accurately reconstruct the displacement fields of the tumor-induced deformation of the host tissue. Thus, we posit the proposed data-driven approach has the potential to greatly reduce the computational overhead of personalized simulations of cancer models, thereby facilitating tumor forecasting, parameter identification, uncertainty quantification, and treatment optimization.

Delay differential equations for the spatially resolved simulation of epidemics with specific application to COVID-19.

In the wake of the 2020 COVID-19 epidemic, much work has been performed on the development of mathematical models for the simulation of the epidemic and of disease models generally. Most works follow the susceptible-infected-removed (SIR) compartmental framework, modeling the epidemic with a system of ordinary differential equations. Alternative formulations using a partial differential equation (PDE) to incorporate both spatial and temporal resolution have also been introduced, with their numerical results showing potentially powerful descriptive and predictive capacity. In the present work, we introduce a new variation to such models by using delay differential equations (DDEs). The dynamics of many infectious diseases, including COVID-19, exhibit delays due to incubation periods and related phenomena. Accordingly, DDE models allow for a natural representation of the problem dynamics, in addition to offering advantages in terms of computational time and modeling, as they eliminate the need for additional, difficult-to-estimate, compartments (such as exposed individuals) to incorporate time delays. In the present work, we introduce a DDE epidemic model in both an ordinary and partial differential equation framework. We present a series of mathematical results assessing the stability of the formulation. We then perform several numerical experiments, validating both the mathematical results and establishing model's ability to reproduce measured data on realistic problems.

Dynamic mode decomposition in adaptive mesh refinement and coarsening simulations.

Dynamic mode decomposition (DMD) is a powerful data-driven method used to extract spatio-temporal coherent structures that dictate a given dynamical system. The method consists of stacking collected temporal snapshots into a matrix and mapping the nonlinear dynamics using a linear operator. The classical procedure considers that snapshots possess the same dimensionality for all the observable data. However, this often does not occur in numerical simulations with adaptive mesh refinement/coarsening schemes (AMR/C). This paper proposes a strategy to enable DMD to extract features from observations with different mesh topologies and dimensions, such as those found in AMR/C simulations. For this purpose, the adaptive snapshots are projected onto the same reference function space, enabling the use of snapshot-based methods such as DMD. The present strategy is applied to challenging AMR/C simulations: a continuous diffusion-reaction epidemiological model for COVID-19, a density-driven gravity current simulation, and a bubble rising problem. We also evaluate the DMD efficiency to reconstruct the dynamics and some relevant quantities of interest. In particular, for the SEIRD model and the bubble rising problem, we evaluate DMD's ability to extrapolate in time (short-time future estimates).

A multi-domain shear-stress dependent diffusive model of cell transport-aided dialysis: analysis and simulation.

Kidney dialysis is the most widespread treatment method for end-stage renal disease, a debilitating health condition common in industrialized societies. While ubiquitous, kidney dialysis suffers from an inability to remove larger toxins, resulting in a gradual buildup of these toxins in dialysis patients, ultimately leading to further health complications. To improve dialysis, hollow fibers incorporating a cell-monolayer with cultured kidney cells have been proposed; however, the design of such a fiber is nontrivial. In particular, the effects of fluid wall-shear stress have an important influence on the ability of the cell layer to transport toxins. In the present work, we introduce a model for cell-transport aided dialysis, incorporating the effects of the shear stress. We analyze the model mathematically and establish its well-posedness. We then present a series of numerical results, which suggest that a hollow-fiber design with a wavy profile may increase the efficiency of the dialysis treatment. We investigate numerically the shape of the wavy channel to maximize the toxin clearance. These results demonstrate the potential for the use of computational models in the study and advancement of renal therapies.

Assessing the Spatio-temporal Spread of COVID-19 via Compartmental Models with Diffusion in Italy, USA, and Brazil.

The outbreak of COVID-19 in 2020 has led to a surge in interest in the mathematical modeling of infectious diseases. Such models are usually defined as compartmental models, in which the population under study is divided into compartments based on qualitative characteristics, with different assumptions about the nature and rate of transfer across compartments. Though most commonly formulated as ordinary differential equation models, in which the compartments depend only on time, recent works have also focused on partial differential equation (PDE) models, incorporating the variation of an epidemic in space. Such research on PDE models within a Susceptible, Infected, Exposed, Recovered, and Deceased framework has led to promising results in reproducing COVID-19 contagion dynamics. In this paper, we assess the robustness of this modeling framework by considering different geometries over more extended periods than in other similar studies. We first validate our code by reproducing previously shown results for Lombardy, Italy. We then focus on the U.S. state of Georgia and on the Brazilian state of Rio de Janeiro, one of the most impacted areas in the world. Our results show good agreement with real-world epidemiological data in both time and space for all regions across major areas and across three different continents, suggesting that the modeling approach is both valid and robust.

Simulating the spread of COVID-19 via a spatially-resolved susceptible-exposed-infected-recovered-deceased (SEIRD) model with heterogeneous diffusion.

We present an early version of a Susceptible-Exposed-Infected-Recovered-Deceased (SEIRD) mathematical model based on partial differential equations coupled with a heterogeneous diffusion model. The model describes the spatio-temporal spread of the COVID-19 pandemic, and aims to capture dynamics also based on human habits and geographical features. To test the model, we compare the outputs generated by a finite-element solver with measured data over the Italian region of Lombardy, which has been heavily impacted by this crisis between February and April 2020. Our results show a strong qualitative agreement between the simulated forecast of the spatio-temporal COVID-19 spread in Lombardy and epidemiological data collected at the municipality level. Additional simulations exploring alternative scenarios for the relaxation of lockdown restrictions suggest that reopening strategies should account for local population densities and the specific dynamics of the contagion. Thus, we argue that data-driven simulations of our model could ultimately inform health authorities to design effective pandemic-arresting measures and anticipate the geographical allocation of crucial medical resources.

Diffusion-reaction compartmental models formulated in a continuum mechanics framework: application to COVID-19, mathematical analysis, and numerical study.

The outbreak of COVID-19 in 2020 has led to a surge in interest in the research of the mathematical modeling of epidemics. Many of the introduced models are so-called compartmental models, in which the total quantities characterizing a certain system may be decomposed into two (or more) species that are distributed into two (or more) homogeneous units called compartments. We propose herein a formulation of compartmental models based on partial differential equations (PDEs) based on concepts familiar to continuum mechanics, interpreting such models in terms of fundamental equations of balance and compatibility, joined by a constitutive relation. We believe that such an interpretation may be useful to aid understanding and interdisciplinary collaboration. We then proceed to focus on a compartmental PDE model of COVID-19 within the newly-introduced framework, beginning with a detailed derivation and explanation. We then analyze the model mathematically, presenting several results concerning its stability and sensitivity to different parameters. We conclude with a series of numerical simulations to support our findings.