Implementing a Surveillance-Based Approach to Create a Statewide Viral Clearance Cascade for Hepatitis C Among People With HIV and HCV Coinfection in Connecticut

Abstract

Objectives:

Highly effective direct-acting antiviral medications have made it feasible to achieve elimination of hepatis C virus (HCV), including for people with HIV and HCV coinfection. The Centers for Disease Control and Prevention offers guidance for a laboratory surveillance–based HCV viral clearance cascade, which allows public health departments to track the outcomes of people with HCV based on the following steps: ever infected, virally tested, initial infection, and cured or cleared. We examined the feasibility of this approach among people with HIV and HCV coinfection in Connecticut.

Methods:

We matched an HIV surveillance database, which included cases from the enhanced HIV/AIDS Reporting System as of December 31, 2019, and the HCV surveillance database, the Connecticut Electronic Disease Surveillance System, to define a cohort of coinfected people. We used HCV laboratory results obtained from January 1, 2016, through August 3, 2020, to determine HCV status.

Results:

Of 1361 people who were ever infected with HCV as of December 31, 2019, 1256 (92.3%) received HCV viral testing, 865 of 1256 people tested (68.9%) were HCV infected, and 336 of 865 infected people (38.8%) were cleared or cured. People who had undetectable HIV viral loads at most recent HIV test (<200 copies/mL) were more likely than those with detectable HIV viral loads to achieve HCV cure (P = .02).

Conclusions:

A surveillance-based approach that includes data based on the Centers for Disease Control and Prevention HCV viral clearance cascade is feasible to implement, can help track population-level outcomes longitudinally, and can help identify gaps to inform HCV elimination strategies.

Keywords

HCV elimination hepatitis C virus cascade surveillance HIV

Hepatitis C is the leading cause of liver-related death in the United States, and people with HIV and hepatitis C virus (HCV) coinfection are >3 times as likely as people with HCV monoinfection to develop and die from liver-related complications.^1-3 Because HIV and HCV have similar transmission routes, the risk of coinfection is high, particularly among people who inject drugs (PWID).¹ Globally, an estimated 2.3 million people with HIV are seropositive for HCV (6.2% of prevalent HIV cases).⁴ In the United States, an estimated 1.2 million people have HIV and 2.4 million people have HCV.⁵ Approximately 25% of people with HIV have chronic HCV infection; the high variability of HIV and HCV coinfection is based on transmission risk factors (eg, prevalence of HIV and HCV coinfection is higher among PWID than among people with HIV who do not inject drugs).^1,6,7 The introduction of direct-acting antiviral medications with a >95% viral cure or clearance rate has revolutionized treatment for people with chronic HCV infection, including people with HIV and HCV coinfection.^8,9 The availability of direct-acting antiviral treatment has led to national and global initiatives aimed at HCV elimination.^9-11 The World Health Organization developed targets for countries to attain HCV elimination by 2030: diagnosing 90% of chronically infected people and curing 80% of diagnosed people.⁴

Cascades of care are graphic representations of diagnosis and treatment milestones for diseases such as HIV.¹² Cascades of care have been used at local, state, and national levels to monitor diagnosis, care, and treatment outcomes and can help identify gaps in services that can be addressed to improve individual and community health outcomes.^13-15 The creation of HIV cascades of care has relied on robust HIV surveillance data.^10-13,16 The 2025 Strategic Plan from the Centers for Disease Control and Prevention (CDC) Division of Viral Hepatitis has prioritized improved hepatitis surveillance and the creation of HCV care cascades.¹⁵ Because a uniform national HCV surveillance database is not yet available, published HCV care cascades have historically focused on monoinfected populations and relied on multiple data sources.¹³ For people with HIV and HCV coinfection, care cascades have generally relied on individual clinic registries, which are useful for tracking clinic performance but do not capture population-level outcomes.^11,13,16-20 A surveillance-based approach using public health department capacity has the theoretical advantage of creating a comprehensive statewide HCV care cascade based on laboratory parameters that correlate with achieving HCV clearance.²¹ CDC has introduced standardized HCV viral clearance guidance that involves leveraging HCV surveillance data from state public health departments.²²

In this study, we applied the CDC HCV viral clearance cascade guidance to people with HIV and HCV coinfection in Connecticut. The cascade includes the following consecutive steps spanning the evaluation and treatment status of HCV based on laboratory parameters: (1) ever infected status (having a positive HCV screen), (2) viral testing status (receipt of polymerase chain reaction [PCR] testing), (3) initial infection status (having a positive PCR test result), and (4) cured or cleared status (having a negative PCR test result). Use of the HCV viral clearance cascade to quantify HCV status and treatment outcomes and highlight existing gaps at the population level is an important step in promoting Data to Care (D2C), a public health strategy that uses surveillance and other data sources to identify and link people with HIV not in care.²³ By implementing the HCV viral clearance cascade, we can expand the use of D2C toward the goal of HCV elimination.

Methods

Surveillance Data Sources

Because most US public health departments report HIV and HCV surveillance data in separate databases, we used 2 surveillance databases for this study. CDC developed the enhanced HIV/AIDS Reporting System (eHARS) for state public health agencies to collect HIV surveillance data, including demographic and laboratory testing details.^24,25 eHARS includes data on people who have ever received a positive test result for HIV and subsequent HIV test results and tracks case investigation information, a requirement for surveillance funding. The Connecticut Electronic Disease Surveillance System (CTEDSS) is the reportable disease repository in Connecticut, including for HCV. The Connecticut Department of Public Health directed reporting of HCV laboratory data on people with any positive test result for HCV (antibody or PCR); negative HCV antibody test results are not reported. In Connecticut, HIV and HCV surveillance began in 1981 and 1994, respectively.

HCV laboratory data are reported electronically or manually. The electronic laboratory reporting (ELR) component of CTEDSS currently facilitates the recording of about 80% of all positive HCV test results (antibody and PCR) and is the primary source of negative HCV PCR test results (for those with initial positive antibody or PCR test results); additional results received via mail or fax are reported manually. We manually entered the backlog of data from all paper-based laboratory data reported during the collection period (January 1, 2016, through August 3, 2020) into CTEDSS before data analysis.

The Yale Human Investigations Committee reviewed the research and deemed it exempt from signed consent requirements because it used deidentified data (institutional review board no. 2000025899). The Connecticut Department of Public Health Human Investigations Committee approved this research project, which used data obtained from the Connecticut Department of Public Health.

Database Linkage

To define the coinfected population, we performed data linkage between eHARS and CTEDSS by using a CDC-developed hierarchical deterministic matching program⁶ with input in SAS version 9.4 (SAS Institute, Inc). The matching methodology involved 14 matching keys, previously created by using various combinations of 4 identifying variables, in whole and in part, for people present in both surveillance systems.²⁶ The 4 variables were first name, last name, date of birth, and social security number. Previous articles have described the matching keys and the matching methodology.^6,26

Project Variables

We collected data on birth year, sex, race and ethnicity, HIV transmission category, and the most recent HIV viral load level to assess differences at each step of the HCV viral clearance cascade. We used deceased and residential status variables to include or exclude people with HIV and HCV coinfection. We collected data on HCV laboratory variables (antibody or PCR test type), test results (positive or negative), and collection date to define HCV laboratory-based testing and treatment status.

HCV Viral Clearance Cascade Steps

We applied the CDC HCV viral clearance cascade steps (Figure 1), which are based on testing and treatment status (dispositions), according to HCV laboratory results (Table 1). The cascade includes 2 evaluation periods (ever infected and follow-up) and 5 steps. For the ever-infected period, we included all people with a positive HCV test result from January 1, 2016, through August 3, 2019. For the follow-up period, we included all data from the ever-infected period plus 1 additional year (ie, January 1, 2016, through August 3, 2020).

Figure 1.

Hepatitis C virus (HCV) clearance cascade. Data source: Centers for Disease Control and Prevention.²² Viral testing includes any HCV RNA, HCV genotype, or HCV core antigen test. (+) is defined as detectable HCV RNA or antigen; (−) is defined as undetectable HCV RNA or antigen. Abbreviations: anti-HCV+, HCV antibody positive; Ag+, antigen positive; RNA+, ribonucleic acid positive.

Table 1.

Disposition creation and steps in the HCV viral clearance cascade using HCV laboratory test results^a

HCV antibody: subsequent HCV PCR test result	Disposition	Viral clearance cascade step^b
Positive
None reported	Antibody+ only	1, 2a
Negative (≥1 PCR) on the same or a later date/specimen	Antibody+, PCR−	1, 2b, 3a
Positive (≥1 PCR) on the same or a later date/specimen	Antibody+, PCR+	1, 2b, 3b, 4a
Positive (≥1 PCR) on the same or a later date/specimen followed by 1 negative PCR	Antibody+, PCR+, PCR−	1, 2b, 3b, 4b
Positive on the same or a later date/specimen followed by ≥2 negative PCRs	Antibody+, PCR+, PCR−	1, 2b, 3b, 4b
Positive on the same date/specimen followed by a later negative PCR followed by another positive PCR (and so on)	Antibody+, PCR+, PCR−, PCR+	1, 2b, 3b, 4b, 5
Negative
None reported	Antibody− only	Excluded
None reported
Negative (≥1 PCR) on the same or a later date/specimen	PCR− only	Excluded
Positive (≥1 PCR) on the same or a later date/specimen	PCR+ only	1, 2b, 3b, 4a
Positive (≥1 PCR) followed by 1 negative PCR on a later date	PCR+, PCR−	1, 2b, 3b, 4b
Positive PCR followed by ≥2 negative PCRs on a later date	PCR+, PCR−	1, 2b, 3b, 4b
Positive PCR followed by a later negative PCR followed by another positive PCR (and so on)	PCR+, PCR−, PCR+	1, 2b, 3b, 4b, 5

Abbreviations: −, negative; +, positive; HCV, hepatitis C virus; PCR, polymerase chain reaction.

Data source: Connecticut Electronic Disease Surveillance System.

Step 1 involved status of ever-infected people who had a positive HCV test result during the period from when reporting of the HCV RNA–negative test result was fully implemented to 1 year before cascade analysis and creation. Step 2 involved viral testing status (performance of PCR testing: PCR performed [2b] or not performed [2a]). Step 3 involved initial infection status based on initial PCR test results, with cleared HCV based on PCR-negative (3a) or initial infection based on PCR-positive (3b) test results. Step 4 involved cured or cleared status based on follow-up PCR, with cured or cleared based on presence of a PCR-negative test result (4b) or not cleared if PCR-negative test result is absent (4a). Step 5 involved persistent infection status based on documentation of PCR-positive test result after previous PCR-negative test result.

Step 1 identifies people ever infected (people who had a positive HCV test result from when HCV RNA–negative test results were routinely collected to 1 year before cascade analysis and creation) (eFigure in Supplemental Material). Step 2 identifies people who were virally tested; people who had PCR testing were categorized as 2b and people who did not have PCR testing were categorized as 2a. Step 3 identifies people with initial infection (based on initial PCR test results); people with cleared HCV (based on a PCR-negative test result) were categorized as 3a and people with initial infection (based on a PCR-positive test result) were categorized as 3b. Step 4 identifies people based on follow-up PCR test results; those who were cured or cleared (based on having a PCR-negative test result) were categorized as 4b and those who were not cured or cleared (based on not having a PCR-negative test result) were categorized as 4a. Step 5 identifies people with persistent infection based on documentation of a PCR-positive test result after a previous PCR-negative test result.

Gaps in evaluation and treatment are represented by people in groups 2a and 4a. The 2a group represents people in need of HCV evaluation through PCR testing. The 4a group represents people with initial infection who remain untreated.

Inclusion and Exclusion Criteria

As specified by CDC guidance, we removed data on deceased people and people who lived outside the jurisdiction (ie, non–Connecticut residents) from the starting cascade (ever-infected group) to better represent the current HCV testing and treatment status of living people coinfected with HIV and HCV in Connecticut. To assess deceased and residential status, we relied on the robustness of eHARS, which is matched quarterly with the state mortality file (vital records) along with yearly matches with the National Death Index and the Social Security Death Index. We also used the CDC Routine Interstate Duplicate Review process, performed every 6 months, to assess residential status. We used prevalent eHARS to automatically exclude people with HIV identified as deceased or out of jurisdiction before linkage to HCV surveillance data. We included prevalent (alive and in-state residents) cases in eHARS as of December 31, 2019 (n = 10 705). Given the 1-year lag to finalize eHARS data, we established the 2019 prevalent eHARS data as the most up-to-date and available at the time of the analysis. We included cases in CTEDSS from January 1, 2016, through August 3, 2020 (n = 28 319); this period aligned with CDC’s guidance on creating the HCV viral clearance cascade, because PCR-negative test results were routinely entered starting in 2016.

Data Analysis

We performed descriptive analysis to examine the distribution of demographic and HIV clinical information variables for the ever-infected group. Our evaluation of each step of the HCV viral clearance cascade depended on dispositions that we created using HCV laboratory results from public health surveillance (CTEDSS). We calculated percentages for each step of the HCV viral clearance cascade relative to the previous step. For example, we calculated viral testing percentages using the number of people ever infected as the denominator, and we calculated the cured or cleared percentages using the number of people with initial infection as the denominator. We used Wald χ² tests to assess demographic differences between those who did or did not receive HCV viral testing and those who achieved or did not achieve HCV cure or clearance, with P ≤ .05 considered significant. We calculated crude odds ratios (ORs) to show relationships of demographic variables in the testing and cured or cleared groups.

Results

Viral Clearance Cascade in Connecticut

The HCV viral clearance cascade for people with HIV and HCV coinfection illustrates overall outcomes by cascade step (Figure 2). Of 1361 people identified in the ever-infected group (step 1), 1256 (92.3%) received HCV viral testing (step 2b). We found some demographic differences in achievement of cascade steps when we compared the overall percentage of each step (Table 2). For example, in step 2b, men who have sex with men (MSM) had a lower rate of HCV viral testing (83.9%) than the overall HCV testing rate (92.3%). For step 3b, 865 of 1256 (68.9%) people who received HCV viral testing were identified in the initial infection group; non-Hispanic Black people (75.6%), PWID (72.2%), people born in 1965 or later (72.3%), men (70.1%), and people with detectable HIV viral loads (79.4%) had higher rates of initial infection than the overall rate (68.9%). Of 865 people with initial infection, we identified 336 (38.8%) people as cured or cleared (step 4b); MSM (35.6%), non-Hispanic Black people (34.2%), and people with detectable HIV viral loads (25.0%) had cured or cleared rates lower than the overall cured or cleared rate (38.8%). Of 336 people identified as cured or cleared, 15 (4.5%) people had persistent infection or reinfection (step 5b); MSM and PWID had the highest rate (18.8%) when compared with the overall persistent infection or reinfection rate (Table 2).

Figure 2.

Hepatitis C virus (HCV) clearance cascade for people with HIV (as of December 31, 2019) and HCV coinfection in Connecticut based on HCV laboratory data from January 1, 2016, through August 3, 2020. Bars show the number of people in each step of the Centers for Disease Control and Prevention HCV clearance cascade.

Table 2.

Conditional proportions of people in Connecticut with HIV and HCV coinfection (as of August 3, 2020) by laboratory-based HCV clearance cascade step^a

Variable	Step, no. (%)^a
Variable	1: ever infected	2b: viral testing	3b: initial infection	4b: cured or cleared	5b: persistent infection or reinfection
Total	1361	1256 (92.3)	865 (68.9)	336 (38.8)	15 (4.5)
Birth year
Before 1965	917	852 (92.9)	573 (67.3)	222 (38.7)	9 (4.1)
1965 and later	444	404 (91.0)	292 (72.3)	114 (39.0)	6 (5.3)
Sex
Female	421	382 (90.7)	252 (66.0)	97 (38.5)	0
Male	940	874 (93.0)	613 (70.1)	239 (39.0)	15 (6.3)
Race and ethnicity
Non-Hispanic Black	448	418 (93.3)	316 (75.6)	108 (34.2)	4 (3.7)
Hispanic	551	509 (92.4)	350 (68.8)	151 (43.1)	9 (6.0)
Other^b	23	21 (91.3)	9 (42.9)	3 (33.3)	0
Non-Hispanic White	339	308 (90.9)	190 (61.7)	74 (38.9)	2 (2.7)
HIV transmission category
Heterosexual	169	151 (89.3)	90 (59.6)	35 (38.9)	0
MSM	124	104 (83.9)	59 (56.7)	21 (35.6)	0
MSM and PWID	62	60 (96.8)	36 (60.0)	16 (44.4)	3 (18.8)
Other/unknown	56	49 (87.5)	36 (73.5)	19 (52.8)	1 (5.3)
PWID	950	892 (93.9)	644 (72.2)	245 (38.0)	11 (4.5)
Most recent HIV viral load level, copies/mL
Detectable, ≥200	143	131 (91.6)	104 (79.4)	26 (25.0)	1 (3.8)
Undetectable, <200	1218	1125 (92.4)	761 (67.6)	310 (40.7)	14 (4.5)

Abbreviations: HCV, hepatitis C virus; MSM, men who have sex with men; PWID, people who inject drugs.

Results show no. or no. (%) of people, with previous step used as the denominator.

Other consisted of people who indicated race and ethnicity as American Indian/Alaska Native, Asian, Native Hawaiian/Pacific Islander, other, or unknown.

Gap Analysis of Clearance Cascade Outcomes

When we compared people who did and did not complete step 2 (had HCV viral testing) in the HCV viral clearance cascade, we observed that MSM (OR = 0.33; 95% CI, 0.19-0.57) and people who identified as heterosexual (OR = 0.53; 95% CI, 0.30-0.92) were significantly less likely than PWID to undergo viral testing (P < .001) (Table 3). For step 4 (cured or cleared status), people with undetectable HIV viral loads on most recent testing were more likely than people with detectable HIV viral loads to be cured or cleared of HCV (OR = 2.06; 95% CI, 1.29-3.29; P < .001). When compared with non-Hispanic White people, Hispanic people were more likely (OR = 1.19; 95% CI, 0.83-1.71) and non-Hispanic Black people were less likely (OR = 0.81; 95% CI, 0.56-1.18) to achieve cured or cleared status, but these results were not significant.

Table 3.

Relationship between birth year, sex, race and ethnicity, HIV transmission category, and most recent HIV viral load and initial HCV viral testing status or cured or cleared of HCV infection status among people with HIV and HCV coinfection, Connecticut, based on laboratory tests from January 1, 2016, through August 3, 2020

Variable	People, no. (%)		OR (95% CI)	People, no. (%)		OR (95% CI)
Variable	Viral testing (n = 1256)	No viral testing (n = 105)	OR (95% CI)	Cured or cleared (n = 336)	Not cured or cleared (n = 529)	OR (95% CI)
Birth year
Before 1966	852 (67.8)	65 (61.9)	1.30 (0.86-1.96)	222 (66.1)	351 (66.4)	0.99 (0.74-1.32)
1966 and later	404 (32.2)	40 (38.1)	1 [Reference]	114 (33.9)	178 (33.6)	1 [Reference]
Sex
Female	382 (30.4)	39 (37.1)	1 [Reference]	97 (28.9)	155 (29.3)	1 [Reference]
Male	874 (69.6)	66 (62.9)	1.35 (0.89-2.05)	239 (71.1)	374 (70.7)	1.02 (0.76-1.38)
Race and ethnicity^a,b
Non-Hispanic Black	418 (33.9)	30 (29.1)	1.40 (0.83-2.37)	108 (32.4)	208 (39.8)	0.81 (0.56-1.18)
Hispanic	509 (41.2)	42 (40.8)	1.22 (0.75-1.98)	151 (45.3)	199 (38.0)	1.19 (0.83-1.71)
Non-Hispanic White	308 (24.9)	31 (30.1)	1 [Reference]	74 (22.2)	116 (22.2)	1 [Reference]
HIV transmission category
Heterosexual	151 (12.0)	18 (17.1)	0.53 (0.30-0.92)^c	35 (10.4)	55 (10.4)	1.04 (0.66-1.63)
MSM	104 (8.3)	20 (19.0)	0.33 (0.19-0.57)^c	21 (6.3)	38 (7.2)	0.90 (0.52-1.57)
MSM and PWID^d	—^e	—^e	—^e	16 (4.8)	20 (3.8)	1.30 (0.66-2.56)
Other/unknown	49 (3.9)	7 (6.7)	0.44 (0.19-1.02)	19 (5.7)	17 (3.2)	1.82 (0.93-3.57)
PWID	952 (75.8)	60 (57.1)	1 [Reference]	245 (72.9)	399 (75.4)	1 [Reference]
Most recent HIV viral load level, copies/mL
Detectable (≥200)	131 (10.4)	12 (11.4)	1 [Reference]	26 (7.7)	78 (14.7)	1 [Reference]
Undetectable (<200)	1125 (89.6)	93 (88.6)	1.11 (0.59-2.08)	310 (92.3)	451 (85.3)	2.06 (1.29-3.29)^f

Abbreviations: HCV, hepatitis C virus; MSM, men who have sex with men; OR, odds ratio; PWID, people who inject drugs.

Does not include 3 classified as other (ie, American Indian/Alaska Native, Asian, Native Hawaiian/Pacific Islander, other, or unknown) with cured or cleared status and 6 classified as other without cured or cleared status.

Does not include 60 classified as other who had viral testing and 2 classified as other who did not have viral testing.

OR significance at P ≤ .05 calculated with Pearson χ² test resulting in P < .001.

MSM and PWID were added to PWID for the viral testing evaluation because of small cell size (60 for viral testing and 2 for no viral testing).

Cell size <5.

OR significance at P ≤ .05 calculated with Pearson χ² test resulting in P = .002.

Discussion

To our knowledge, this study represents the first implementation of CDC’s HCV viral clearance cascade guidance using laboratory surveillance data to track people with HIV and HCV coinfection. We tracked HCV status based on laboratory data collected from January 1, 2016, through August 3, 2020, among a cohort of people with HIV in Connecticut (prevalent cases as of December 31, 2019) and estimated an HCV cured or cleared rate of 38.8% among people identified with HCV infection at initial PCR test.

Creating an HCV care cascade is a key recommended approach in the 2025 Strategic Plan developed by CDC’s Division of Viral Hepatitis.¹⁵ Among various approaches to the creation of HCV care cascades, published clinic-based cascades with cured or cleared rates >50% have the advantage of granular clinical data, enabling documentation of additional steps in the cascade (eg, treatment status).^17-20,27 Large data registries from international collaborations with multiple clinics have also shown marked improvements in cured or cleared rates because of widespread access to direct-acting antiviral treatment and national strategic HCV microelimination plans.^27-33 Such efforts require dedicated resources not available to most clinics in US public health departments, which are often inadequately resourced for tracking serial HCV testing. Nonetheless, a surveillance-based approach has the advantage of avoiding reliance on the labor-intensive extraction of data by clinic or other dedicated staff.^13,17,28 Surveillance data can also provide population-level estimates that show progression from diagnosis to cure and can harness additional data (eg, demographic characteristics, geographic trends) to define outcomes and understand gaps.

Addressing identified gaps in the viral clearance cascade involves multiple approaches, including enhanced collaborations between public health departments and individual clinics, the heart of the D2C paradigm. D2C, which was developed for public health agencies to improve the HIV care continuum, uses existing HIV surveillance to identify and reengage out-of-care people with HIV.²³ Reengagement strategies are critical, as shown in a meta-analysis that highlighted that active reengagement strategies increased patient return to care by 20% as compared with the standard of care.³⁴ The interface between public health departments and clinics can provide a forum to address D2C opportunities identified in the HCV viral clearance cascade. For example, we found that people with HIV transmission categories other than PWID (eg, MSM, heterosexual) were significantly less likely to receive HCV viral testing than PWID. Additionally, those with undetectable HIV viral loads were significantly more likely to be cured or cleared of HCV infection than those with detectable HIV viral loads. Promoting the cost-effectiveness of risk-based HCV screening with inclusion of reflex PCR testing for antibody-positive test results may explain the increased viral testing for PWID and constitutes a best practice to improve viral testing.³⁵ Suboptimal engagement in HIV care may explain the lack of cure for people with detectable HIV. Falade-Nwulia et al²⁷ reported that HCV elimination was impeded by gaps in the HIV care continuum (eg, missed appointments). Similarly, Rizk et al¹⁷ noted that missed HIV appointments were more common among people with HIV who were not treated for HCV than among people with HIV who were treated for HCV. More detailed characterization of people who have not successfully achieved HCV cure or clearance is needed.^36-38 Clinic-based strategies such as care facilitation have been successfully used to improve HCV cure.^39,40

Communication between public health departments and clinics to promote improvements in the viral clearance cascade can vary. One approach involves public health department communication with clinics through a case conferencing strategy and has been used to improve HIV care continuum outcomes.⁴¹ In another study of people with HIV and HCV coinfection conducted at 11 clinics in Connecticut (inclusive of HCV treatment status as of September 2020), we used the case conferencing approach to develop a clinic-based HCV care cascade.⁴² We found that clinic-based HCV care cascades had rates of HCV cure that were higher than those found in the present study’s jurisdictional viral clearance cascade.⁴² Specifically, the combined HCV cure rate in these clinics was 73% (range, 44%-100%) versus 38.8% for the statewide population in the present study.⁴² This finding may indicate that more granular data are available at the clinic level and highlight the need for more complete data systems to accurately calculate population-level HCV outcomes. The interface between public health departments and clinics created by case conferencing can lead to a more accurate understanding of the true HCV cleared or cured rate in Connecticut.

The uniform guidance provided by CDC’s HCV viral clearance cascade differs from previously published HCV cascades of care. The ability to refine the cascade based on deceased and residential status optimizes the design to reflect real-time needs and gaps in testing and treatment. Using this guidance, we assessed the current HCV cure rate of living residents in the jurisdiction instead of the cumulative cure rates calculated from previously published cascades.^43,44 In contrast to HIV care cascades, only people with initial HCV infection are included in the denominator to determine the cured or cleared rate; for people with HIV, all those who receive a positive test result for HIV are included in the denominator when calculating the viral suppression rate. Both cascades face temporal challenges in which treatment and care status changes with time and requires regular updating. Lack of HIV and HCV data integration (eg, data silos, lack of clinical data) can also affect the reliability of cascade estimates; more comprehensive data integration approaches have the potential to improve cascade analyses.⁴⁵ Our ability to detect the role of demographic variables in estimates of HCV cure rates relied on more comprehensive data available from the eHARS database. Historically, a lack of funding in the United States for HCV surveillance has led to incomplete demographic information and substantial data lags (lack of recording of PCR-negative test results). These HCV surveillance database issues will pose challenges to the creation of HCV viral clearance cascades for the larger HCV monoinfected population.

Progress has been made to advance the development of HCV surveillance databases critical for creating HCV viral clearance cascades. In an expansion of this project, we applied the methods for HCV care cascade creation to 7 public health jurisdictions in the United States (Yale University, unpublished data, 2022). The greatest challenge faced by jurisdictions was allocating resources needed to upgrade their HCV surveillance database, including data updates (specifically for reporting of PCR-negative test results). Innovations in this area have been designed, particularly for acute HCV surveillance.⁴⁶ Recently, public health departments have addressed this challenge by using new CDC funding to hire HCV surveillance staff. HCV elimination plans have been developed by jurisdictions throughout the United States with proposed innovations to meet elimination goals.²¹ Innovations include increasing ELR with HCV PCR-negative test results, developing data sharing among public health entities, and integrating multiple infectious disease databases. Creating data interfaces between electronic medical records and public health surveillance is another innovation in development.²¹ Guidance on HCV viral clearance cascades based on laboratory surveillance and related training strategies have been distributed to all CDC-funded public health departments.

Limitations

Our study had several limitations. First, surveillance-based methodology relies on the robustness of data reporting. In Connecticut, the ELR interface for HCV testing, the mechanism for reporting PCR-negative test results, accounts for approximately 80% of all HCV laboratory tests performed and, thus, is incomplete, leading to an underestimate of the cured or cleared rate. This underestimate is consistent with our previous analysis, in which an HCV care cascade was created for coinfected people using only HCV surveillance data reported through ELR (reported from January 1, 2015, through December 31, 2019); in this HCV care cascade, the cured or cleared rate was 69.2%.⁴⁷ The inherent likelihood of data entry errors and lags in HCV surveillance reporting could lead to misclassification of patients. Surveillance-based data are consistent with proposed consensus cascade definitions, which focus solely on easily defined HCV outcomes, such as infected, diagnosed, and cured. Such data lack specifics on coexisting clinical conditions (eg, concurrent substance use disorders) and social determinants of health (eg, housing, health insurance), which can substantially affect access to and initiation of treatment.⁴⁸ Second, data on those who lack HCV cure cannot distinguish whether people are currently in treatment or whether treatment was not yet started. Analysis of HIV transmission categories is based on reports from initial infection and may not reflect changes in current transmission risk for HIV or HCV.

Conclusions

We implemented the CDC guidance on creating an HCV viral clearance cascade and adapted it for people with HIV and HCV coinfection in Connecticut. This surveillance-based approach can be used to track longitudinal changes in cascade outcomes and help identify population-level gaps that can inform further strategies to promote HCV elimination.

Supplemental Material

sj-pdf-1-phr-10.1177_00333549231172173 – Supplemental material for Implementing a Surveillance-Based Approach to Create a Statewide Viral Clearance Cascade for Hepatitis C Among People With HIV and HCV Coinfection in Connecticut

Supplemental material, sj-pdf-1-phr-10.1177_00333549231172173 for Implementing a Surveillance-Based Approach to Create a Statewide Viral Clearance Cascade for Hepatitis C Among People With HIV and HCV Coinfection in Connecticut by Maximilian Wegener, Ralph Brooks, Suzanne Speers, Lisa Nichols and Merceditas Villanueva in Public Health Reports

Footnotes

Acknowledgements

The authors thank Alexei Zelenev, PhD, Yale University School of Medicine, for helpful comments.

Disclaimer

The Connecticut Department of Public Health does not endorse or assume any responsibility for any analyses, interpretations, or conclusions based on the data. The authors assume full responsibility for all such analyses, interpretations, and conclusions.

Declaration of Conflicting Interests

The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Funding

The authors disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: This study was supported by the Health Resources and Services Administration of the US Department of Health and Human Services as part of HRSA-17-047 Special Projects of National Significance, under award U90HA31462, totaling $2 300 000, with no percentage financed with nongovernmental sources.

ORCID iD

Maximilian Wegener, MPH

Supplemental Material

Supplemental material for this article is available online. The authors have provided these supplemental materials to give readers additional information about their work. These materials have not been edited or formatted by Public Health Reports’s scientific editors and, thus, may not conform to the guidelines of the AMA Manual of Style, 11th Edition.

References

Cowan

Herman

Rahman

Zahn

Leider

Calderon

. Bundled HIV and hepatitis C testing in the emergency department: a randomized controlled trial. West J Emerg Med. 2018;19(6):1049-1056. doi:10.5811/westjem.2018.8.37827

Kronfli

Bhatnagar

Hull

, et al. Trends in cause-specific mortality in HIV–hepatitis C coinfection following hepatitis C treatment scale-up. AIDS. 2019;33(6):1013-1022. doi:10.1097/qad.0000000000002156

Hughes

Jiles

Holmberg

. Rising mortality associated with hepatitis C virus in the United States, 2003-2013. Clin Infect Dis. 2016;62(10):1287-1288. doi:10.1093/cid/ciw111

World Health Organization. Global health sector strategy on viral hepatitis 2016-2021: towards ending viral hepatitis. May 17, 2016. Accessed September 25, 2020. https://www.who.int/publications/i/item/WHO-HIV-2016.06

Centers for Disease Control and Prevention. Estimated HIV incidence and prevalence in the United States, 2015-2019. HIV Surveill Rep Suppl Rep. 2021;26(1):1-81. Accessed October 22, 2021. http://www.cdc.gov/hiv/library/reports/hiv-surveillance.html

Bosh

Coyle

Hansen

, et al. HIV and viral hepatitis coinfection analysis using surveillance data from 15 US states and two cities. Epidemiol Infect. 2018;146(7):920-930. doi:10.1017/S0950268818000766

Centers for Disease Control and Prevention. People coinfected with HIV and viral hepatitis. Updated September 21, 2020. Accessed September 25, 2020. https://www.cdc.gov/hepatitis/populations/hiv.htm

Falade-Nwulia

Suarez-Cuervo

Nelson

Fried

Segal

Sulkowski

. Oral direct-acting agent therapy for hepatitis C virus infection: a systematic review. Ann Intern Med. 2017;166(9):637-648. doi:10.7326/M16-2575

Pawlotsky

. Hepatitis C drugs: is next generation the last generation? Gastroenterology. 2016;151(4):587-590. doi:10.1053/j.gastro.2016.08.043

10.

Platt

Easterbrook

Gower

, et al. Prevalence and burden of HCV co-infection in people living with HIV: a global systematic review and meta-analysis. Lancet Infect Dis. 2016;16(7):797-808. doi:10.1016/S1473-3099(15)00485-5

11.

Perlman

Jordan

Nash

. Conceptualizing care continua: lessons from HIV, hepatitis C virus, tuberculosis and implications for the development of improved care and prevention continua. Front Public Health. 2017;4:296. doi:10.3389/fpubh.2016.00296

12.

Giordano

. The HIV treatment cascade—a new tool in HIV prevention. JAMA Intern Med. 2015;175(4):596-597. doi:10.1001/jamainternmed.2014.8199

13.

Yehia

Schranz

Umscheid

. The treatment cascade for chronic hepatitis C virus infection in the United States: a systematic review and meta-analysis. PLoS One. 2014;9(7):e101554. doi:10.1371/journal.pone.0101554

14.

Subbaraman

Nathavitharana

Mayer

, et al. Constructing care cascades for active tuberculosis: a strategy for program monitoring and identifying gaps in quality of care. PLoS Med. 2019;16(2):e1002754. doi:10.1371/journal.pmed.1002754

15.

Centers for Disease Control and Prevention, Division of Viral Hepatitis. 2025 Strategic plan. 2020. Accessed October 22, 2021. https://www.cdc.gov/hepatitis/pdfs/DVH-StrategicPlan2020-2025.pdf

16.

Prussing

Chan

Pinchoff

, et al. HIV and viral hepatitis co-infection in New York City, 2000-2010: prevalence and case characteristics. Epidemiol Infect. 2015;143(7):1408-1416. doi:10.1017/S0950268814002209

17.

Rizk

Miceli

Shiferaw

, et al. Implementing a comprehensive hepatitis C virus (HCV) clinic within a human immunodeficiency virus clinic: a model of care for HCV microelimination. Open Forum Infect Dis. 2019;6(10):ofz361. doi:10.1093/ofid/ofz361

18.

Beck

Kim

Khalili

. Direct acting antivirals improve HCV treatment initiation and adherence among underserved African Americans. Ann Hepatol. 2018;17(3):413-418. doi:10.5604/01.3001.0011.7385

19.

Berenguer

Rodríguez-Castellano

Carrero

, et al. Eradication of hepatitis C virus and non–liver-related non-acquired immune deficiency syndrome–related events in human immunodeficiency virus/hepatitis C virus coinfection. Hepatology. 2017;66(2):344-356. doi:10.1002/hep.29071

20.

Zuckerman

Douglas

Nwosu

Choi

Chastain

. Increasing success and evolving barriers in the hepatitis C cascade of care during the direct acting antiviral era. PLoS One. 2018;13(6):e0199174. doi:10.1371/journal.pone.0199174

21.

Gowda

. Strategies for the elimination of hepatitis C virus infection as a public health threat in the United States. Curr Hepatol Rep. 2018;17(2):111-120. doi:10.1007/s11901-018-0394-x

22.

Montgomery

Sizemore

Wingate

, et al. Development of a standardized, laboratory result–based hepatitis C virus clearance cascade for public health jurisdictions. Public Health Rep. Posted online May 4, 2023. doi:10/1177/00333549231170044

23.

Centers for Disease Control and Prevention. Data to Care program guidance: using HIV surveillance data to support the HIV care continuum. 2017. Accessed January 24, 2023. https://www.cdc.gov/hiv/pdf/funding/announcements/ps18-1802/CDC-HIV-PS18-1802-AttachmentJ-Data-to-Care-Program-Guidance.pdf

24.

Sweeney

Hoyte

Mulatu

, et al. Implementing a Data to Care strategy to improve health outcomes for people with HIV: a report from the Care and Prevention in the United States demonstration project. Public Health Rep. 2018;133(2):60S-74S. doi:10.1177/0033354918805987

25.

Centers for Disease Control and Prevention. HIV Statistics Center surveillance overview: HIV surveillance and monitoring systems. Updated July 28, 2022. Accessed November 19, 2022. https://www.cdc.gov/hiv/statistics/surveillance/index.html

26.

Bosh

Coyle

Muriithi

, et al. Linking HIV and viral hepatitis surveillance data: evaluating a standard, deterministic matching algorithm using data from 6 US health jurisdictions. Am J Epidemiol. 2018;187(11):2415-2422. doi:10.1093/aje/kwy161

27.

Falade-Nwulia

Sutcliffe

Mehta

, et al. Hepatitis C elimination in people with HIV is contingent on closing gaps in the HIV continuum. Open Forum Infect Dis. 2019;6(10):ofz426. doi:10.1093/ofid/ofz426

28.

Boerekamps

Van Den Berk

Lauw

, et al. Declining hepatitis C virus (HCV) incidence in Dutch human immunodeficiency virus–positive men who have sex with men after unrestricted access to HCV therapy. Clin Infect Dis. 2018;66(9):1360-1365. doi:10.1093/cid/cix1007

29.

Doyle

Van Santen

Iser

, et al. Microelimination of hepatitis C among people with human immunodeficiency virus coinfection: declining incidence and prevalence accompanying a multicenter treatment scale-up trial. Clin Infect Dis. 2021;73(7):e2164-e2172. doi:10.1093/cid/ciaa1500

30.

Smit

Boyd

Rijnders

, et al. HCV micro-elimination in individuals with HIV in the Netherlands 4 years after universal access to direct-acting antivirals: a retrospective cohort study. Lancet HIV. 2021;8(2):e96-e105. doi:10.1016/S2352-3018(20)30301-5

31.

Braun

Hampel

Ledergerber

, et al. A treatment-as-prevention trial to eliminate hepatitis C among men who have sex with men living with human immunodeficiency virus (HIV) in the Swiss HIV Cohort Study. Clin Infect Dis. 2021;73(7):e2194-e2202. doi:10.1093/cid/ciaa1124

32.

Fursa

Mocroft

Lazarus

, et al. The hepatitis C cascade of care in HIV/hepatitis C virus coinfected individuals in Europe: regional and intra-regional differences. AIDS. 2022;36(3):423-435. doi:10.1097/QAD.0000000000003112

33.

Haley

Edmonds

Ramirez

, et al. Direct-acting antiviral hepatitis C treatment cascade and barriers to treatment initiation among US men and women with and without HIV. J Infect Dis. 2021;223(12):2136-2144. doi:10.1093/infdis/jiaa686

34.

Mirzazadeh

Eshun-Wilson

Thompson

, et al. Interventions to reengage people living with HIV who are lost to follow-up from HIV treatment programs: a systematic review and meta-analysis. PLoS Med. 2022;19(3):e1003940. doi:10.1371/journal.pmed.1003940

35.

Tatar

Keeshin

Mailliard

Wilson

. Cost-effectiveness of universal and targeted hepatitis C virus screening in the United States. JAMA Netw Open. 2020;3(9):e2015756. doi:10.1001/jamanetworkopen.2020

36.

Linas

Barter

Leff

, et al. The hepatitis C cascade of care: identifying priorities to improve clinical outcomes. PLoS One. 2014;9(5):e97317. doi:10.1371/journal.pone.0097317

37.

Calner

Sperring

Ruiz-Mercado

, et al. HCV screening, linkage to care, and treatment patterns at different sites across one academic medical center. PLoS One. 2019;14(7):e0218388. doi:10.1371/journal.pone.0218388

38.

Webster

Moore

Bocour

Johnsons

Winters

. Health department efforts to increase hepatitis C RNA testing among people appearing out of care: comparison of outreach approaches, New York City, 2017. Public Health Rep. 2020;135(6):823-830. doi:10.1177/0033354920952068

39.

Sherbuk

McManus

Rogawski-Mcquade

Knick

Henry

Dillingham

. Hepatitis C within a single health system: progression along the cascade to cure is higher for those with substance misuse when linked to a clinic with embedded support services. Open Forum Infect Dis. 2018;5(9):ofy202. doi:10.1093/ofid/ofy202

40.

Metsch

Feaster

Gooden

, et al. Care facilitation advances movement along the hepatitis C care continuum for persons with human immunodeficiency virus, hepatitis C, and substance use: a randomized clinical trial (CTN-0064). Open Forum Infect Dis. 2021;8(8):ofab334. doi:10.1093/ofid/ofab334

41.

Fanfair

Khalil

Williams

, et al. The Cooperative Re-Engagement Controlled trial (CoRECT): a randomized trial to assess a collaborative Data to Care model to improve HIV care continuum outcomes. Lancet Reg Health Am. 2021;3:100057. doi:10.1016/j.lana.2021.100057

42.

Brooks

Wegener

Speers

, et al. Creating a longitudinal HCV care cascade for persons with HIV/HCV co-infection in selected HIV clinics using Data to Care methods. Health Promot Pract. 2023;24(5):1039–1049. doi:10.1177/15248399231169792

43.

Thomas

. State of the hepatitis C virus care cascade. Clin Liver Dis. 2020;16(1):8-11. doi:10.1002/cld.915

44.

Moore

Bocour

Laraque

Winters

. A surveillance-based hepatitis C care cascade, New York City, 2017. Public Health Rep. 2018;133(4):497-501. doi:10.1177/0033354918776641

45.

Baer

Fagalde

Drake

, et al. Design of an enhanced public health surveillance system for hepatitis C virus elimination in King County, Washington. Public Health Rep. 2020;135(1):33-39. doi:10.1177/0033354919889981

46.

Lewis

Eason

Barbeau

Boulton

Nakashima

Dunn

. Enhancing surveillance protocols for acute hepatitis C virus infection, Utah, 2014-2019. Public Health Rep. Published online June 9, 2022. doi:10.1177/00333549221101381

47.

Wegener

Brooks

Speers

Nichols

Villanueva

. A sustainable surveillance-based approach to creating a state-level HCV cascade of care for HIV/HCV co-infected persons. Preprint. Posted online August 26, 2021. SSRN. doi:10.2139/ssrn.3911823

48.

Safreed-Harmon

Blach

Aleman

, et al. The consensus hepatitis C cascade of care: standardized reporting to monitor progress toward elimination. Clin Infect Dis. 2019;69(12):2218-2227. doi:10.1093/cid/ciz714

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