ANALYSIS OF HEPATITIS C VIRUS (HCV) EPIDEMIOLOGY AMONG YOUNG PRESCRIPTION OPIOD USERS IN RHODE ISLAND, AND MODELLING OF HCV TREATMENT SCALE-UP.

Soipe, Ayorinde

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Year:: 2017
Contributor:: Soipe, Ayorinde (creator); Taylor, Lynn (Reader); Marshall, Brandon (Advisor); Brown University. Department of Epidemiology (sponsor)
Genre:: theses
Subject:: Epidemiology; Public health; Rhode Island; hepatitis c virus; non-medical use of prescription opioids; elimination; testing; modeling; linkage to care; treatment; young adults; scale-up; mathematical modelling
Extent:: 10, 68 p.
DOI: https://doi.org/10.7301/Z05Q4TJG

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Abstract:: THESIS OVERVIEW Hepatitis C virus (HCV) infection leads to a number of clinical conditions including acute hepatitis, chronic hepatitis, cirrhosis of the liver, and liver cancer (1). HCV belongs to the Hepacivirus genus of viruses, under a family of viruses known as Flaviviridae (2). Six distinct HCV genotypes are presently identified: genotypes 1 to 6. Genotype 1 is the most prevalent worldwide, accounting for 46.2% of all HCV cases globally, while genotype 3 accounts for 30.1% of all HCV cases globally (3). The largest proportions of genotypes 4 and 5 have been mapped to low-income countries (3). In the United States (US), approximately 70% of chronic HCV infections are caused by genotype 1, 15 to 20% by genotype 2, 10 to 12% genotype 3, 1% genotype 4, and less than 1% genotype 5 or 6 (4). The replicative process of the virus occurs in the cytosol of the host liver cell. Upon successful replication and release into the bloodstream, the virus is most commonly spread through percutaneous exposure to infectious blood, for example through sharing of unsterilized infected needles (5). In addition to parenteral means, sexual mode of HCV transmission has been documented to occur primarily in HIV co-infected men who have sex with men (6, 7). Data from under-resourced countries indicate iatrogenic cause as a common means of HCV transmission in such settings (8). The incidence of both acute and chronic HCV infection rose dramatically in the US through the 1970s and 1980s, and chronic HCV prevalence is particularly high among individuals born between 1945 and 1965 popularly described as the “baby boomers” (9, 10). Persons born between this time period account for approximately 75% of all HCV infections in the US (10). The morbidity and mortality attributed to HCV infection have also been significantly higher among this demographic (11). The disproportionately high burden of chronic HCV infection among “baby boomers” has been suggested to result from infections acquired between the 1960s and 1980s, following the use of medical equipment or procedures before universal precautions and infection control procedures were adopted (12). Instances of transfusing HCV-infected blood to patients prior to the introduction of mandatory screening of blood for HCV in 1992 also played an additional role in the spread of the infection to other population demographics (13). Beginning in the early 2000’s, a bimodal age distribution in the prevalence of HCV infection began to appear in the US (14). A newer HCV-infected cohort has since been described, which mainly comprised of young persons who inject drugs (PWIDs). The evolving demographic led to a re-emergence of incident HCV infection epidemic in several US regions (15). The rapid increase in new HCV infections among PWIDs has been attributed to the ongoing opioid crisis across the US (16). A significant number of acute HCV infection acquisition among young drug users was fueled by this nationwide opioid crisis. This cohort of HCV-infected persons has attracted public health attention because injection drug use and syringe sharing behavior increase the risk of HCV transmission among young adult drug users (17), thus perpetuating the spread of the infection. As concerns continue to grow regarding the need to curb further spread of HCV infection among PWIDs, numerous studies have shown the effectiveness of HCV treatment as a viable means for HCV prevention among PWIDs (18). Therefore, early testing and treatment of HCV ought to be encouraged because early detection and treatment of HCV among young persons will reduce HCV transmission to other young individuals (19, 20). Up until a few years ago, the treatment regimen for HCV was mainly based on the use of two medications: pegylated interferon and ribavirin (21). These medications have been associated with severe side effects including hematological, systemic, and psychiatric adverse effects (22, 23) However, there have been advances in terms of medications available to treat HCV with the approval of direct acting antivirals (DAAs) by the Food and Drug Administration. A major milestone was the approval of the first DAA to be used without interferon in December 2013 (24). DAAs achieve high sustained viral response (SVR) rates in persons with HCV infection (25). SVR is achieved when there are undetectable HCV-RNA at the end of therapy and this describes a state of HCV cure (26). In addition, DAAs facilitate shorter treatment duration thus lowering cost per cure (27). By extension, the treatment effects achieved by DAAs reduce the risk for hepatocellular carcinoma, liver-related mortality, and overall mortality (28). The antiviral activity of these agents is via the inhibition of vital enzymes involved in the replicative process of the virus (29). DAAs have varying levels of antiviral activity against HCV genotypes. Patients infected with HCV genotype 3 are the least responsive to both DAAs and the older HCV treatment regimen (30, 31). The pan-genomic properties of the newer DAAs however, allow for simpler, shorter, less toxic, and broad treatment of HCV genotypes (25). Despite the scientific breakthrough in HCV treatment, several barriers limit access to the novel medications, thereby hindering efforts to achieve cure. These barriers can be categorized as patient-level barriers (for example poor knowledge and inaccurate perceptions about HCV), system-level barriers (for example limited reimbursements available to HCV care providers), and provider-level barriers (for example lack of provider knowledge of prescribing HCV treatment) (32-34). In sum, the burden of HCV infection has attracted much attention on a national and global level. More people in the U.S. are now dying of HCV than all other top 60 infectious diseases combined (35). This observation underscores the need to aspire towards attaining a scenario where HCV infection spread is substantially curbed, and the virus eventually eliminated. To tackle the re-emerging HCV epidemic partly fueled by the nationwide prescription opioid crisis, it is important to find, evaluate, and treat HCV-infected PWIDs. Treating PWIDs in the early stages of liver disease is effective and saves cost (36). To this end, this thesis is a two-part analysis of HCV epidemiology in Rhode Island. The first examines HCV testing and care experience among young adults who use prescription opioids non-medically, amidst the current opioid and overdose crisis in Rhode Island. It describes the prevalence of HCV screening, confirmatory testing, and referral to care among young adults who use prescription opioids non-medically. The second part of this thesis presents strategies that can be employed in preventing further spread of the disease and eventually eliminating the disease in Rhode Island. A mathematical modeling approach was used to describe the amount of scale up in HCV treatment needed to achieve a substantial reduction in the burden of chronic HCV infection. Both studies underscore the fact that, with the discovery of highly effective anti-HCV medications, it is possible to achieve HCV elimination by instituting policy changes targeted at the barriers limiting access to the medications. 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Notes:: Thesis (Sc. M.)--Brown University, 2017

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Soipe, Ayorinde, "ANALYSIS OF HEPATITIS C VIRUS (HCV) EPIDEMIOLOGY AMONG YOUNG PRESCRIPTION OPIOD USERS IN RHODE ISLAND, AND MODELLING OF HCV TREATMENT SCALE-UP." (2017). Epidemiology Theses and Dissertations. Brown Digital Repository. Brown University Library. https://doi.org/10.7301/Z05Q4TJG

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Epidemiology Theses and Dissertations

Theses and Dissertations for the Epidemiology department.
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