Hepatitis C Virus (HCV) is a flavivirus that can cause both acute and chronic infections which, if untreated, can progressively lead to liver damage, liver cirrhosis, and hepatocellular carcinoma (HCC). With the recent opioid epidemic in the US, there has been an increase in cases of HCV in both the adult and adolescent populations. This has resulted in an increase in HCV infections in women of childbearing age, and mother-to-child transmission occurs in 2-7% of pregnancies in women who are HCV-infected. Approximately 40% of children with chronic HCV infection are expected to clear the virus, and the remainder will develop a chronic infection that will persist into adulthood if untreated 3. The American Association for the Study of Liver Diseases (AASLD) currently recommends Direct-Acting Antivirals (DAAs) to treat chronic HCV infection for all children 3 years of age and older, which cures >90% of individuals. However current risk-based screening strategies among children born to mothers with HCV are inadequate in identifying the majority of children born with HCV. We assessed the cost-effectiveness analysis of universal HCV screening among children at age 2 compared to the status quo- risk-based screening in the U.S.

Background: With the World Health Organization (WHO) hepatitis C virus (HCV) global elimination goals to reduce HCV incidence and mortality by 2030, there is an urgent need to consider disproportionately affected populations including people who inject drugs (PWID) and HIV-infected individuals. Although curative direct-acting antiviral (DAA) treatments for HCV are now available, barriers to access and affordability have slowed progress towards achieving the WHO goals, particularly in low-middle income country (LMIC) settings where the vast majority of HCV burden resides. This thesis uses modeling to inform HCV elimination programs among vulnerable populations in LMIC settings.

Objectives: Specific aims of this dissertation include: (1) to determine what combination intervention scale-up is needed to achieve the WHO HCV elimination goals among current and former PWID in Tijuana, Mexico; (2) to evaluate the cost-effectiveness of HCV incidence elimination strategies among PWID in Tijuana, Mexico; (3) to evaluate real-world cost and cost-effectiveness of DAAs for HCV/HIV-coinfected individuals in Dawei, Myanmar.

Methods: In Chapter 2, I used a dynamic, deterministic model of HCV transmission, progression, and harm reduction. In Chapter 3, I extended the model in Chapter 2 to perform a cost-effectiveness analysis of HCV elimination strategies from a healthcare provider perspective among PWID in Tijuana, Mexico. In Chapter 4, I performed a micro-costing analysis of an HCV treatment program among HIV-infected individuals in Dawei, Myanmar and used a Markov model to evaluate the cost-effectiveness of this program compared to no treatment.

Results: In Chapter 2, findings showed that achieving both HCV incidence and mortality elimination goals in Tijuana required additional DAA investment. Further, combination harm reduction scale-up plus DAAs required fewer treatments compared to DAAs alone, so may be more feasible given limited treatment allocation nationally. In Chapter 3, results showed that all elimination strategies were cost-effective in Tijuana. While a treatment only strategy was the least costly, combination harm reduction and treatment provided more health benefits compared to treatment alone and is cost-effective. Chapter 4 findings demonstrated that HCV DAA treatment for HCV/HIV-coinfected individuals was cost-effective in Myanmar, and even more so with simplified treatment algorithms.

Conclusions: Findings from these studies highlight the feasibility and cost-effectiveness of HCV elimination programs for PWID and HIV-positive individuals in two LMIC settings. Expansion of HCV screening and treatment programs for these populations are urgently required, coupled with evidence-based harm reduction interventions to prevent reinfection and ensure that the WHO HCV elimination goals are achieved by 2030.

Background: People who inject drugs (PWID) are at an increased risk of human immunodeficiency virus (HIV) and hepatitis C virus (HCV) from sharing of blood contaminated injection equipment and are defined by the World Health Organization as a key population for focus of prevention efforts for the UNAIDS HIV and WHO HCV 2030 targets.1-3 Despite evidence that harm reduction program such as needle and syringe programs (NSPs) and supervised consumption sites (SCS) reduce injecting risk, coverage of NSPs is low globally and SCS are only available in a few countries.4-6 To support expansion of these harm reduction interventions, research is needed to fill data gaps that remain in regards to the cost of implementation in many countries, how the COVID-19 pandemic impacted utilization of harm reduction services, and potential impact of the establishment of SCS on HIV and HCV among PWID..Methods: In Aim 1, we performed a global systematic review on the unit cost of NSP provision and used statistical modeling with the extracted cost estimates to predict the united cost per syringe distributed for 137 countries. In Aim 2, we used a longitudinal cohort of PWID in San Diego, California (La Frontera) to examine the changes during the COVID-19 pandemic of the risk environment, including access to harm reduction services and injecting risk. In Aim 3, we developed a dynamic HIV and HCV transmission model, to simulate the potential 10-year impact of establishment and scale-up of SCS to 20% coverage among PWID on future HIV and HCV incidence within three counties in California: San Francisco, Los Angeles, and San Diego. Results: In Aim 1, 55 estimates of the unit cost per syringe were collected from the literature from 14 countries and the unit costs were extrapolated for 137 countries, ranging from $0.08 to $20.77 (2020 USD) per syringe distributed. From Aim 2, from the 336 PWID enrolled in the La Frontera cohort who resided in San Diego at baseline and had at least one study follow-up visit, baseline harm reduction access was low (6% accessed NSP services, 10% received OAT), and over 12-months post-baseline we observed a decrease in receptive syringe sharing, an increase in recent NSP access, no change in OAT access, and a decrease in injecting heroin. In Aim 3, we scale-up of SCS coverage to 20% among PWID in three counties (San Francisco, Los Angeles, and San Diego) in California resulted in a decrease of new HIV infections (22%, 15%, and 14%, respectively) and new HCV infections (28%, 32%, and 27%, respectively) among PWID over 10 years. Conclusion: Harm reduction services are an important component of preventing the spread of HIV and HCV among PWID. By understanding the costs associated with implementation of NSPs, how the COVID-19 pandemic impacted utilization of harm reduction services, and the impact of SCS on HIV and HCV transmission, policies and funding can be established to help reach the UNAIDS HIV and the WHO HCV 2030 goals.

Background: Incarceration is associated with increased risk of hepatitis C virus (HCV) among people who inject drugs (PWID). If properly implemented, public health oriented drug law reforms can reduce adverse health outcomes among PWID. This dissertation investigates (1) the cumulative effect of repeated incarceration on injecting risks among PWID in Tijuana; (2) the potential impact of implementing Mexico’s drug law reform on the HCV epidemic among PWID in Tijuana; and (3) the impact of a police education program on the burden of HCV among PWID in Tijuana. Methods: Chapter 2 examines the longitudinal association between cumulative incarceration with receptive syringe sharing using cohort data among PWID in Tijuana. Chapter 3 presents a mathematical model of incarceration and HCV transmission among PWID to estimate the 10-year population attributable fraction of incarceration to HCV incidence among PWID, and the impact of implementing drug law reform on HCV incidence among PWID in Tijuana. Chapter 4 estimates the impact of a real-life police education program on HCV disease burden among PWID in Tijuana, using epidemic modeling. Results: Chapter 2 showed every additional incarceration episode increased the odds of syringe sharing by 17% (95% confidence interval [CI] 1.05-1.29). The increased odds of receptive syringe sharing persisted up to 1.5 years post-incarceration. Chapter 3 projected that incarceration is associated with 5.4% (95% uncertainty interval [UI] 0.6-11.9%) of new HCV infections among PWID in Tijuana between 2022–2032. Also, fully implemented drug law reforms (decriminalization and OAT diversion) could reduce HCV incidence rate by 10.6% (UI: 3.1-19.2%) across 10 years. Chapter 4 showed that, over the 2-year implementation, Escudo reduced HCV incidence from 21.1 per 100 person years (/100py) (UI 17–27/100py) in 2016 to 20.7/100py (UI:16-26/100py) in 2018, averting 13 (UI: 3-26) infections from 2016-2018. Using a 50-year time horizon, a 2-year reduction in incarceration from Escudo could avert a total of 120 (UI: 19-260) cases of cirrhosis. Conclusions: These findings broaden the knowledge of the deleterious effects of incarceration on the health of PWID and inform evidence-based policymaking and interventions at the intersection of drug law reform, policing, and injection drug use.

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