Modeling hepatitis C micro-elimination among people who inject drugs with direct-acting antivirals in metropolitan Chicago

Hepatitis C virus (HCV) infection is a leading cause of chronic liver disease and mortality worldwide. Direct-acting antiviral (DAA) therapy leads to high cure rates. However, persons who inject drugs (PWID) are at risk for reinfection after cure and may require multiple DAA treatments to reach the World Health Organization’s (WHO) goal of HCV elimination by 2030. Using an agent-based model (ABM) that accounts for the complex interplay of demographic factors, risk behaviors, social networks, and geographic location for HCV transmission among PWID, we examined the combination(s) of DAA enrollment (2.5%, 5%, 7.5%, 10%), adherence (60%, 70%, 80%, 90%) and frequency of DAA treatment courses needed to achieve the WHO’s goal of reducing incident chronic infections by 90% by 2030 among a large population of PWID from Chicago, IL and surrounding suburbs. We also estimated the economic DAA costs associated with each scenario. Our results indicate that a DAA treatment rate of >7.5% per year with 90% adherence results in 75% of enrolled PWID requiring only a single DAA course; however 19% would require 2 courses, 5%, 3 courses and <2%, 4 courses, with an overall DAA cost of $325 million to achieve the WHO goal in metropolitan Chicago. We estimate a 28% increase in the overall DAA cost under low adherence (70%) compared to high adherence (90%). Our modeling results have important public health implications for HCV elimination among U.S. PWID. Using a range of feasible treatment enrollment and adherence rates, we report robust findings supporting the need to address re-exposure and reinfection among PWID to reduce HCV incidence

Defining nutrient co-location typologies for human-derived supply and crop demands to advance resource recovery

Resource recovery from human excreta can advance circular economies while improving access to sanitation and renewable agricultural inputs. Proximity between human-derived nutrient supply and crop nutrient demands influence how nutrients are recovered in order to be a competitive alternative to synthetic fertilizers. For 107 countries, we analyze the co-location of human-derived nutrients and crop demands for nitrogen, phosphorus, and potassium. To characterize co-location patterns, we fit data for each country to a generalized logistic function. We identified three typologies: (i) dislocated nutrient production and demand resulting from high density agriculture (with low population density) and nutrient islands (e.g., high density cities) requiring nutrient concentration and transport; (ii) co-located nutrient production and demand enabling local reuse; and (iii) countries spanning the continuum between these two extremes. Finally, we explored connections between these typologies and country-specific contextual characteristics via principal component analysis (PCA) and found the human development index (HDI) was a strong indicator of the country’s affiliated typology based on its nutrient landscape. By providing a generalizable, quantitative framework for characterizing the co-location of excreted nutrients and agricultural needs, these typologies can advance resource recovery by informing resource recovery strategies, investment, and enabling policies.U of I OnlyAuthor requested U of Illinois access only (OA after 2yrs) in Vireo ETD syste

Model parameters.

<p>* In sensitivity analysis we keep the relationship θ = 1000*μ to maintain a steady population size.</p><p>** Calibrated for each population to produce the empirically observed prevalence rate before initiation of antiviral scale-up.</p><p>Model parameters.</p

Mathematical Modeling of Hepatitis C Prevalence Reduction with Antiviral Treatment Scale-Up in Persons Who Inject Drugs in Metropolitan Chicago

<div><p>Background/Aim</p><p>New direct-acting antivirals (DAAs) provide an opportunity to combat hepatitis C virus (HCV) infection in persons who inject drugs (PWID). Here we use a mathematical model to predict the impact of a DAA-treatment scale-up on HCV prevalence among PWID and the estimated cost in metropolitan Chicago.</p><p>Methods</p><p>To estimate the HCV antibody and HCV-RNA (chronic infection) prevalence among the metropolitan Chicago PWID population, we used empirical data from three large epidemiological studies. Cost of DAAs is assumed $50,000 per person.</p><p>Results</p><p>Approximately 32,000 PWID reside in metropolitan Chicago with an estimated HCV-RNA prevalence of 47$50-$77] in the overall PWID population, 19 per 1,000 [$20-$26] for persons in HR programs, and 5 per 1,000 [$3-$4] for young PWID.</p><p>Conclusions</p><p>Treatment scale-up could dramatically reduce the prevalence of chronic HCV infection among PWID in Chicago, who are the main reservoir for on-going HCV transmission. Focusing treatment on PWID attending HR programs and/or young PWID could have a significant impact on HCV prevalence in these subpopulations at an attainable cost.</p></div

The effect of immunity (parameter ξ) on HCV-RNA prevalence.

<p>With no immunity (i.e., ξ = 0) HCV-RNA prevalence reaches steady state at 40% (solid black line). When 50% or 80% of cases result in immunity, HCV-RNA prevalence reaches steady state at 34% (solid gray line) or 31% (dashed gray line), respectively. All other model parameters were set as shown in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0135901#pone.0135901.t001" target="_blank">Table 1</a> and π = 0.192. The simulations were initiated with one HCV-infected individual until it reached steady state with no treatment scale-up. On the x-axis each rectangle represents 50 years.</p

Schematic description of Martin et al. [17] mathematical model.

<p>N represents the total PWID population (X+Tr+Z+C₁+C₂). Model parameters are described in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0135901#pone.0135901.t001" target="_blank">Table 1</a>.</p

Resulting H_RNAP after 10, 20 and 30 years of treating 10 infections per 1000 PWID with 90% SVR rate, 12-week treatment duration and acquired immunity (ξ = 0.8).

<p>Predicted effect from Chicago’s overall baseline H_RNAP (47%), Chicago’s harm reduction (HR) attending PWID (30%) and Chicago’s subpopulation with low baseline H_RNAP (10%).</p

Prevalence and treatment scale-up estimates.

<p>HR, PWID in harm reduction programs;</p><p>^@, based on the population estimate from Tempalski et al [<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0135901#pone.0135901.ref020" target="_blank">20</a>];</p><p>IQR, interquartile range;</p><p>^A, data from the CDC-sponsored National HIV Behavioral Surveillance System (NHBS09) of 2009;</p><p>^B data from the Third Collaborative Injection Drug Users (CIDUS III) study;</p><p>^C was calculated using H_RNAP~H_ABP *(1- ξδ) where ξ = 0.8 and δ = 0.26;</p><p>^D, based on empirical data of HCV-RNA and HCV-Ab measurements (see <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0135901#sec006" target="_blank">Methods</a>) which translated into δ = 0.34 [<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0135901#pone.0135901.ref025" target="_blank">25</a>]; M, million;</p><p>** based on sensitivity analysis (<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0135901#pone.0135901.s004" target="_blank">S2</a>–<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0135901#pone.0135901.s008" target="_blank">S6</a> Tables).</p><p>*Note that sub-populations are overlapping (see <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0135901#sec017" target="_blank">Discussion</a>).</p><p>Prevalence and treatment scale-up estimates.</p