Estimating the impact of HIV PrEP regimens containing long-acting injectable cabotegravir or daily oral tenofovir disoproxil fumarate/emtricitabine among men who have sex with men in the United States: a mathematical modelling study for HPTN 083.

Background: The HPTN 083 trial demonstrated superiority of HIV pre-exposure prophylaxis (PrEP) containing long-acting injectable cabotegravir (CAB) to daily oral tenofovir disoproxil fumarate/emtricitabine (TDF/FTC) among men who have sex with men (MSM). We compared the potential population-level impact of TDF/FTC and CAB among MSM in Atlanta, Georgia.

Methods: An MSM HIV transmission model was calibrated to Atlanta-specific data on HIV prevalence and PrEP usage (percentage of uninfected MSM on PrEP), assuming only PrEP-indicated MSM used PrEP.

Estimating benefits of using on-demand oral prep by MSM: A comparative modeling study of the US and Thailand.

Background: Daily and on-demand pre-exposure prophylaxis (PrEP) are effective at preventing HIV acquisition among men who have sex with men (MSM), but only daily PrEP is approved in the US. On-demand PrEP may improve uptake and adherence. We identify sub-groups of MSM who would benefit from on-demand PrEP and determine effectiveness achieved if individuals used their optimal regimens.

Bayesian validation framework for dynamic epidemic models.

Complex models of infectious diseases are used to understand the transmission dynamics of the disease, project the course of an epidemic, predict the effect of interventions and/or provide information for power calculations of community level intervention studies. However, there have been relatively few opportunities to rigorously evaluate the predictions of such models till now. Indeed, while there is a large literature on calibration (fitting model parameters) and validation (comparing model outputs to data) of complex models based on empirical data, the lack of uniformity in accepted criteria for such procedures for models of infectious diseases has led to simple procedures being prevalent for such steps.

Identifying Regions of Greatest Need for Ending the HIV Epidemic: A Plan for America.

Background: In the 2019 State of the Union Address, President Trump announced a plan for "Ending the HIV Epidemic" in the United States, with a goal to reduce new HIV infections by 90% by 2030. Phase I of the plan set an intermediate goal of a 75% reduction within 5 years, focusing on select states and counties.

Methods: We assessed the feasibility of the first phase of the plan by estimating the fraction of HIV diagnoses that occur within the targeted region, using a statistical model to predict new HIV cases in each county.

The dynamics of a simple, risk-structured HIV model.

Many diseases, such as HIV, are heterogeneous for risk. In this paper, we study an infectious-disease model for a population with demography, mass-action incidence, an arbitrary number of risk classes, and separable mixing. We complement our general analyses with two specific examples.

The future of a partially effective HIV vaccine: assessing limitations at the population level.

Objectives: Mathematical models have unanimously predicted that a first-generation HIV vaccine would be useful and cost-effective to roll out, but that its overall impact would be insufficient to reverse the epidemic. Here, we explore what factors contribute most to limiting the impact of such a vaccine.

Methods: Ranging from a theoretical ideal to a more realistic regimen, mirroring the one used in the currently ongoing trial in South Africa (HVTN 702), we model a nested hierarchy of vaccine attributes such as speed of scale-up, efficacy, durability, and return rates for booster doses.

Targeting and vaccine durability are key for population-level impact and cost-effectiveness of a pox-protein HIV vaccine regimen in South Africa.

Background: RV144 is to date the only HIV vaccine trial to demonstrate efficacy, albeit rapidly waning over time. The HVTN 702 trial is currently evaluating in South Africa a similar vaccine formulation to that of RV144 for subtype C HIV with additional boosters (pox-protein regimen). Using a detailed stochastic individual-based network model of disease transmission calibrated to the HIV epidemic, we investigate population-level impact and maximum cost of an HIV vaccine to remain cost-effective.

Assessing the utility of the tipping point ratio to monitor HIV treatment programmes in the era of universal access to ART.

Background: The epidemiological tipping point ratio (TPR) has been suggested as a useful indicator to monitor the scale-up of antiretroviral treatment (ART) programmes and determine when scale-up is sufficient to control the epidemic. TPR has been defined as the ratio of yearly number of new HIV infections to the yearly number of new ART initiations or to the yearly net increase in the number of people on ART. It has been used to rank the progress of treatment programmes across countries, with the objective of reaching a TPR value under 1.

The impact and cost-effectiveness of controlling cholera through the use of oral cholera vaccines in urban Bangladesh: A disease modeling and economic analysis.

Background: Cholera remains an important public health problem in major cities in Bangladesh, especially in slum areas. In response to growing interest among local policymakers to control this disease, this study estimated the impact and cost-effectiveness of preventive cholera vaccination over a ten-year period in a high-risk slum population in Dhaka to inform decisions about the use of oral cholera vaccines as a key tool in reducing cholera risk in such populations.

Methodology/principal Findings: Assuming use of a two-dose killed whole-cell oral cholera vaccine to be produced locally, the number of cholera cases and deaths averted was estimated for three target group options (1-4 year olds, 1-14 year olds, and all persons 1+), using cholera incidence data from Dhaka, estimates of vaccination coverage rates from the literature, and a dynamic model of cholera transmission based on data from Matlab, which incorporates herd effects.

Projected effectiveness and added value of HIV vaccination campaigns in South Africa: A modeling study.

Promising multi-dose HIV vaccine regimens are being tested in trials in South Africa. We estimated the potential epidemiological and economic impact of HIV vaccine campaigns compared to continuous vaccination, assuming that vaccine efficacy is transient and dependent on immune response. We used a dynamic economic mathematical model of HIV transmission calibrated to 2012 epidemiological data to simulate vaccination with anticipated antiretroviral treatment scale-up in South Africa.

Recruitment of Female Sex Workers in HIV Prevention Trials: Can Efficacy Endpoints Be Reached More Efficiently?

Background/setting: Randomized controlled trials (RCTs) of HIV biomedical prevention interventions often enroll participants with varying levels of HIV exposure, including people never exposed to HIV. We assessed whether enrolling larger proportion of participants with consistently high exposure to HIV, such as female sex workers (FSWs), might reduce trial duration and improve the accuracy of product efficacy estimates in future HIV prevention trials.

Methods: We used an individual-based stochastic model to simulate event-driven RCTs of an HIV prevention intervention providing 80% reduction in susceptibility per act under different proportions of FSW enrolled.

Impact of Population Recruitment on the HIV Epidemics and the Effectiveness of HIV Prevention Interventions.

Mechanistic mathematical models are increasingly used to evaluate the effectiveness of different interventions for HIV prevention and to inform public health decisions. By focusing exclusively on the impact of the interventions, the importance of the demographic processes in these studies is often underestimated. In this paper, we use simple deterministic models to assess the effectiveness of pre-exposure prophylaxis in reducing the HIV transmission and to explore the influence of the recruitment mechanisms on the epidemic and effectiveness projections.

How Much Do We Know about Drug Resistance Due to PrEP Use? Analysis of Experts' Opinion and Its Influence on the Projected Public Health Impact.

Background: Randomized controlled trials reported that pre-exposure prophylaxis (PrEP) with tenofovir and emtricitabine rarely selects for drug resistance. However, drug resistance due to PrEP is not completely understood. In daily practice, PrEP will not be used under the well-controlled conditions available in the trials, suggesting that widespread use of PrEP can result in increased drug resistance.

Seasonality and the effectiveness of mass vaccination.

Many infectious diseases have seasonal outbreaks, which may be driven by cyclical environmental conditions (e.g., an annual rainy season) or human behavior (e.

PrEP Adherence Patterns Strongly Affect Individual HIV Risk and Observed Efficacy in Randomized Clinical Trials.

Background: Randomized controlled trials (RCTs) suggest that the efficacy of tenofovir-based preexposure prophylaxis (PrEP) strongly depends on the consistency of PrEP use. We explore how the patterns of pill taking and waning of PrEP protection may affect PrEP efficacy for HIV prevention.

Methods: A 2-arm RCT was simulated by mathematical models assuming that the prescribed daily doses were skipped periodically, randomly, or in large blocks.

A curative regimen would decrease HIV prevalence but not HIV incidence unless targeted to an ART-naïve population.

HIV curative strategies currently under development aim to eradicate latent provirus, or prevent viral replication, progression to AIDS, and transmission. The impact of implementing curative programs on HIV epidemics has not been considered. We developed a mathematical model of heterosexual HIV transmission to evaluate the independent and synergistic impact of ART, HIV prevention interventions and cure on HIV prevalence and incidence.

Comparative effectiveness of different strategies of oral cholera vaccination in bangladesh: a modeling study.

Background: Killed, oral cholera vaccines have proven safe and effective, and several large-scale mass cholera vaccination efforts have demonstrated the feasibility of widespread deployment. This study uses a mathematical model of cholera transmission in Bangladesh to examine the effectiveness of potential vaccination strategies.

Methods & Findings: We developed an age-structured mathematical model of cholera transmission and calibrated it to reproduce the dynamics of cholera in Matlab, Bangladesh.

What can mathematical models tell us about the relationship between circular migrations and HIV transmission dynamics?

Circular migrations are the periodic movement of individuals between multiple locations, observed in parts of sub-Saharan Africa. Relationships between circular migrations and HIV are complex, entailing interactions between migration frequency, partnership structure, and exposure to acute HIV infection. Mathematical modeling is a useful tool for understanding these interactions.

Mathematical insights in evaluating state dependent effectiveness of HIV prevention interventions.

Mathematical models have been used to simulate HIV transmission and to study the use of preexposure prophylaxis (PrEP) for HIV prevention. Often a single intervention outcome over 10 years has been used to evaluate the effectiveness of PrEP interventions. However, different metrics express a wide variation over time and often disagree in their forecast on the success of the intervention.

Beating the placebo in HIV prevention efficacy trials: the role of the minimal efficacy bound.

Objectives: To produce an effect on the HIV epidemic, preventive interventions need to achieve a minimum level of efficacy to offset potential indirect effects such as an increase in risky behavior. The current generation of HIV prevention trials on oral preexposure prophylaxis and on vaginal microbicides were designed using different set points for minimum individual-level efficacy (MIE). Some trials were designed not only to show superiority over placebo but also to rule out lower efficacies.

Modeling the gender-specific impact of vaginal microbicides on HIV transmission.

Vaginal microbicides (VMB) are currently among the few women-initiated biomedical interventions for preventing heterosexual transmission of HIV. In this paper we use a deterministic model of HIV transmission to assess the public-health benefits of a VMB intervention and evaluate its gender-specific impact over short (initial) and extended periods of time. We define two distinct quantitative benefit ratios (QBRs) based on infections prevented in men and women to create and study regions of male advantage in different parameter spaces.

Who will Benefit from a Wide-Scale Introduction of Vaginal Microbicides in Developing Countries?

Vaginal microbicides (VMB) are currently among the few biomedical interventions designed to help women reduce their risk of acquiring HIV infection. However, the microbicide containing antiretroviral (ARV-VMB) may lead to the development of antiretroviral resistance and could paradoxically become more beneficial to men at the population level. We developed a mathematical model to study the impact of a wide-scale population usage of VMB in a heterosexual population.

Bat population dynamics: multilevel model based on individuals' energetics.

Temperate-zone bats are subject to serious energetic constraints due to their high surface area to volume relations, the cost of temperature regulation, the high metabolic cost of flight, and the seasonality of their resources. We present a novel, multilevel theoretical approach that integrates information on bat biology collected at a lower level of organization, the individual with its physiological characteristics, into a modeling framework at a higher level, the population. Our individual component describes the growth of an individual female bat by modeling the dynamics of the main body compartments (lipids, proteins, and carbohydrates).