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 Colocation Typologies for Human-Derived Supply and Crop Demand To Advance Resource Recovery.

Resource recovery from human excreta can advance circular economies while improving access to sanitation and renewable agricultural inputs. While national projections of nutrient recovery potential provide motivation for resource recovery sanitation, elucidating generalizable strategies for sustainable implementation requires a deeper understanding of country-specific overlap between supply and demand. For 107 countries, we analyze the colocation of human-derived nutrients (in urine) and crop demands for nitrogen, phosphorus, and potassium. To characterize colocation patterns, we fit data for each country to a generalized logistic function. Using fitted logistic curve parameters, three typologies were identified: (i) dislocated nutrient supply and demand resulting from high density agriculture (with low population density) and nutrient islands (e.g., dense cities) motivating nutrient concentration and transport; (ii) colocated nutrient supply and demand enabling local reuse; and (iii) diverse nutrient supply-demand proximities, with countries spanning the continuum between (i) and (ii). Finally, we explored connections between these typologies and country-specific contextual characteristics via principal component analysis and found that the Human Development Index was clustered by typology. By providing a generalizable, quantitative framework for characterizing the colocation of human-derived nutrient supply and agricultural nutrient demand, these typologies can advance resource recovery by informing resource management strategies, policy, and investment.

Modeling indicates efficient vaccine-based interventions for the elimination of hepatitis C virus among persons who inject drugs in metropolitan Chicago.

BACKGROUND AND AIMS: Persons who inject drugs (PWID) are at highest risk for acquiring and transmitting hepatitis C (HCV) infection. The recent availability of oral direct-acting antiviral (DAA) therapy with reported cure rates >90% can prevent HCV transmission, making HCV elimination an attainable goal among PWID. The World Health Organization (WHO) recently proposed a 90% reduction in HCV incidence as a key objective. However, given barriers to the use of DAAs in PWID, including cost, restricted access to DAAs, and risk of reinfection, combination strategies including the availability of effective vaccines are needed to eradicate HCV as a public health threat. This study aims to model the cost and efficacy of a dual modality approach using HCV vaccines combined with DAAs to reduce HCV incidence by 90% and prevalence by 50% in PWID populations. METHODS: We developed a mathematical model that represents the HCV epidemic among PWID and calibrated it to empirical data from metropolitan Chicago, Illinois. Four medical interventions were considered: vaccination of HCV naive PWID, DAA treatment, DAA treatment followed by vaccination, and, a combination of vaccination and DAA treatment. RESULTS: The combination of vaccination and DAAs is the lowest cost-expensive intervention for achieving the WHO target of 90% incidence reduction. The use of DAAs without a vaccine is much less cost-effective with the additional risk of reinfection after treatment. Vaccination of naïve PWID alone, even when scaled-up to all reachable PWID, cannot achieve 90% reduction of incidence in high-prevalence populations due to infections occurring before vaccination. Similarly, the lowest cost-expensive way to halve prevalence in 15 years is through the combination of vaccination and DAAs. CONCLUSIONS: The modeling results underscore the importance of developing an effective HCV vaccine and augmenting DAAs with vaccines in HCV intervention strategies in order to achieve efficient reductions in incidence and prevalence.

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

BACKGROUND/AIM: 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. METHODS: 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. RESULTS: Approximately 32,000 PWID reside in metropolitan Chicago with an estimated HCV-RNA prevalence of 47% or 15,040 cases. Approximately 22,000 PWID (69% of the total PWID population) attend harm reduction (HR) programs, such as syringe exchange programs, and have an estimated HCV-RNA prevalence of 30%. There are about 11,000 young PWID (<30 years old) with an estimated HCV-RNA prevalence of 10% (PWID in these two subpopulations overlap). The model suggests that the following treatment scale-up is needed to reduce the baseline HCV-RNA prevalence by one-half over 10 years of treatment [cost per year, min-max in millions]: 35 per 1,000 [$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. CONCLUSIONS: 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.