Abstract
BACKGROUND:
The goal of hepatitis C virus (HCV) treatment is to cure the patient of the infection, defined as a nondetectable HCV RNA at least 12 weeks after treatment completion, or sustained virologic response (SVR). The COVID-19 pandemic has presented new barriers to care in the treatment of patients with HCV that resulted in a transition to tele-health services at many health systems to overcome these barriers.
OBJECTIVE:
To assess the real-world impact of the COVID-19 pandemic and the subsequent shift to a telehealth model on collection of SVR data and other HCV treatment outcomes in a health-system setting.
METHODS:
Subjects who received a referral for an HCV direct-acting antiviral agent between January 1, 2018, and November 30, 2020, and were aged 18 years or older at time of enrollment were placed in either “pre–COVID-19” or “COVID-19” cohorts based on enrollment date. The primary endpoint of this study evaluated confirmed SVR to treatment determined by the absence of HCV RNA by polymerase chain reaction testing at least 12 weeks after completion of drug therapy. Secondary endpoints evaluated completion of medication therapy and adherence to laboratory appointments.
RESULTS:
1,504 patients met study inclusion criteria (pre–COVID-19 cohort, n = 1,230; COVID-19 cohort, n = 274). The COVID-19 cohort demonstrated significantly lower therapy completion rates (P = 0.001), were less likely to obtain SVR laboratory tests (P < 0.001), and had a significantly lower confirmed SVR rate (P < 0.001) compared with the pre–COVID-19 cohort. In a subset of patients who completed therapy and had SVR laboratory tests collected, there were no significant differences observed in the rate of patients who achieved SVR (P = 0.959).
CONCLUSIONS:
During the COVID-19 pandemic, patients with HCV were significantly less likely to complete therapy or participate in SVR laboratory work. Further studies are needed to determine if offering a telehealth option for our patients in a post–COVID-19 environment would offer any additional advantage in increasing access to care for patients with HCV.
Plain language summary
The COVID-19 pandemic introduced barriers to health care access and encouraged telehealth services to promote social distancing. The impact of these changes on patients with hepatitis C has yet to be fully described. This study compares patients treated for hepatitis C via telehealth services during the COVID-19 pandemic with patients receiving in-person, pre-pandemic treatment at an academic health system. Patients with hepatitis C during the COVID-19 pandemic were significantly less likely to complete therapy, obtain laboratory tests, and achieve a clinical-defined cure. Further study is needed to determine which factors introduced by the pandemic most affected outcomes for patients with hepatitis C virus (HCV).
Implications for managed care pharmacy
The findings of this study suggest that services provided to patients with HCV during the early stages of the COVID-19 pandemic were less effective as compared with previous years. It remains to be seen whether these negative outcomes can be attributed to provision of care via telehealth or systemic barriers to health care access caused by the COVID-19 pandemic. Managed care pharmacists should be aware of this ongoing disparity in outcomes when designing services targeted toward patients with HCV.
Hepatitis C is an infection of the liver caused by the hepatitis C virus (HCV), which can cause mild to severe acute and chronic hepatitis that can last a lifetime if untreated.1 The World Health Organization estimates that 30% of infected people spontaneously clear the virus within 6 months of being infected without any treatment; however, the remaining 70% of infected persons can develop chronic HCV and subsequently are at risk for complications such as cirrhosis or hepatocellular carcinoma.1 Centers for Disease Control and Prevention HCV surveillance data show a steady and significant increase in new HCV infections from 2010 to 2019.2 This significant increase in new HCV infections has primarily resulted from the ongoing opioid epidemic and the associated injection drug use, particularly among young adults.2-5 In 2019, a total of 4,136 new cases of acute HCV were reported from a total of 44 states, with an estimate of 57,500 total new acute cases of HCV in 2019 alone after adjusting for under-ascertainment and underreporting.2 An estimated 2.4 million persons are living with acute HCV infection, which corresponds to just under 1% HCV prevalence among the US adult population.6 Approximately 45% of people who are infected with HCV are unaware of their HCV status.7
Since the discovery of HCV more than 30 years ago, major advances have been made towards treating the virus. HCV treatment has improved from a success rate of only 6% with interferon alone in 1986 to more than 80% in 2013 with triple combination direct-acting antiviral (DAA) therapies.9 Now, with pangenotypic DAA regimens, such as sofosbuvir/velpatasvir and glecaprevir/pibrentasvir, overall cure rates are as high as 98% in treatment-naive patients without uncompensated cirrhosis.10,11 The current goal of HCV treatment is to reduce liver-related complications by achieving a cure as determined by a sustained virologic response (SVR), defined as the absence of HCV RNA by polymerase chain reaction testing at least 12 weeks after completion of drug therapy. However, even with higher efficacy drug therapies to treat HCV, significant barriers still exist in treating patients who are currently infected with HCV and assessing SVR in patients with HCV who complete treatment regimens.
UK HealthCare is an academic medical center located in Lexington, Kentucky, that serves patients throughout Kentucky and bordering states. In the state of Kentucky in 2016, HCV prevalence was estimated to be 1.25% compared with 0.93% in the United States overall,8 leading to a higher proportion of HCV patients in our patient population. HCV treatments prescribed by health system providers are managed by our health-system specialty pharmacy. More than 70% of our patients with HCV receive health care coverage through Medicaid programs, and 20% reside in rural areas.
Prior to the COVID-19 pandemic, all patients receiving care at our health system would meet with providers and pharmacists in clinic prior to and when starting treatment for HCV. However, to facilitate social distancing efforts during the pandemic, we transitioned to a decentralized telehealth model. Telehealth models have been previously used to successfully reach rural and underserved populations while promoting minimal direct contact.12,13 It was hypothesized that moving to provision of care via telehealth would lessen the impact of systemic barriers to care created by the COVID-19 pandemic. This study explores the effect of COVID-19 and the shift to virtual services on HCV outcomes at our health-system specialty pharmacy.
Methods
PROVISION OF HCV CLINICAL SERVICES
HCV patient management at our health-system specialty pharmacy is initiated with a “meet and greet” clinic visit between patient and pharmacist. During this visit, relevant demographic information is collected and expectations for the course of therapy are outlined for the patient. If the pharmacist and provider agree that the patient is appropriate for therapy, a referral is then sent to centralized specialty pharmacy staff. Subsequently, a patient care coordinator performs a benefits investigation and submits any necessary prior authorizations. Once approval is obtained, a second visit with the patient is performed by the pharmacist in which initial medication counseling is provided. During counseling, patients are provided disease-state and medication-specific education, a treatment calendar outlining provider visits and laboratory work, and a written management plan for any allergies, drug interactions, or adverse drug reactions.
Typical follow-up for a patient includes laboratory work scheduled at 2 weeks into treatment (TW2), end of treatment (EOT), and 12 weeks following completion of therapy (SVR12). Pharmacists also contact the patient at treatment week 2, treatment week 4, treatment week 8 (if using a 12-week regimen), and EOT via telephone for assessment check-ins. During check-ins, pharmacists provide adherence coaching, potential side effects management, and coordinate any changes to the laboratory work schedule.
Prior to March 15, 2020, initial “meet and greet” and counseling visits, as well as laboratory testing, were conducted in person at internal health-system sites, with follow-up assessments (TW2, EOT, and SVR12) conducted via telephone. On March 15, 2020, operational procedures were adjusted by the health-system in response to the COVID-19 pandemic. Subsequently, all scheduled clinic visits were conducted entirely via telehealth, and laboratory/diagnostic testing visits were scheduled with both internal and external health care institutions, whichever was most convenient for the patient. Specialty pharmacy communications via telephone continued as they had prior to this transition.
PATIENT POPULATION
This retrospective cohort study was conducted to examine subjects who were enrolled in the health-system specialty pharmacy’s Infectious Disease management program between January 1, 2018, and November 30, 2020, who received a prescription for an HCV DAA written by a health-system provider and were aged 18 years or older at the time of enrollment. Patients who initiated therapy between January 1, 2018, and March 14, 2020, were included in the pre–COVID-19 cohort, and patients who started therapy between March 15, 2020, and November 30, 2020, were grouped in the COVID-19 cohort.
DATA COLLECTION AND ANALYSIS
Initial clinical assessments were extracted from the health-system specialty pharmacy patient management system (TherigySTM). These initial clinical assessments correspond to initial medication counseling sessions for patients starting an HCV regimen. The following data elements were further extracted from the patient management system: age, sex, ethnicity, patient filling at health-system specialty pharmacy or external pharmacy, payer group (commercial, Medicare, Medicaid, and other), patient-reported therapy completion status during pharmacist telehealth appointment, discontinuation reason, and SVR status.
Data collected were used to assess rates of completion of DAA and final laboratory test collection visits, as well as rates of SVR at 12 weeks posttreatment. Subgroup analyses were performed to assess a final laboratory test collection in patients who completed therapy and SVR in patients who completed therapy and had final laboratory tests drawn. Data were analyzed in IBM SPSS Statistics Version 27. Categorical data were analyzed using the Pearson chi-square or Fisher exact test, as appropriate. Continuous variables were analyzed using independent sample differences of medians test or independent samples t-tests, as appropriate. Statistical significance was defined as P < 0.05. Before data collection, the study was approved by the University of Kentucky Institutional Review Board.
Results
A total of 1,504 patients were identified who met inclusion criteria and were included in the final analysis (Figure 1). Of this group, 1,230 of the patients were included in the pre–COVID-19 cohort and 274 were included in the COVID-19 cohort (Table 1). The COVID-19 cohort was significantly younger than the pre–COVID-19 cohort (mean age 38 vs 41 respectively; P = 0.009). When ethnicity was analyzed as a categorical variable, a significant difference between the pre-COVID and post-COVID cohorts was noted (P = 0.006); however, when analyzed as dichotomous based on White vs non-White patients, no significant difference was observed (P = 0.443).
FIGURE 1.
Study Population and Attrition by Cohort
TABLE 1.
Demographics
| Pre-COVID-19 | COVID-19 | Total | P value | |
|---|---|---|---|---|
| Age | ||||
| N | 1,230 | 274 | 1,504 | 0.009 |
| Median (IQR) | 41 (33-54) | 38 (32-51) | 41 (33-53) | |
| Range | 18.0, 86.0 | 20.0, 75.0 | 18.0, 86.0 | |
| Sex, n (%) | ||||
| Male | 695 (56.5) | 155 (56.5) | 850 (56.5) | 0.984 |
| Female | 535 (43.5) | 119 (43.5) | 654 (43.5) | |
| Ethnicity, n (%) | ||||
| White | 1,114 (90.6) | 244 (89.1) | 1,358 (90.3) | 0.006 |
| African American | 107 (8.7) | 21 (7.7) | 128 (8.5) | |
| Hispanic/Latino | 7 (0.6) | 5 (1.8) | 12 (0.8) | |
| Asian | 2 (0.2) | 4 (1.5) | 6 (0.4) | |
| White/Non-White, n (%) | ||||
| White | 1,114 (90.6) | 244 (89.1) | 1,358 (90.3) | 0.443 |
| Non-White | 116 (9.4) | 30 (10.9) | 146 (9.7) | |
| Type of HCV therapy, n (%) | ||||
| Glecaprevir/pibrentasvir | 680 (55.3) | 77 (28.1) | 757 (50.3) | < 0.001 |
| Sofosbuvir/velpatasvir | 370 (30.1) | 187 (68.2) | 557 (37.0) | |
| Ledipasvir/sofosbuvir | 146 (11.9) | 4 (1.5) | 150 (10.0) | |
| Sofosbuvir/velpatasvir/voxilaprevir | 14 (1.1) | 3 (1.1) | 17 (1.1) | |
| Sofosbuvir/velpatasvir/ribavarin | 11 (0.9) | 3 (1.1) | 14 (1.0) | |
| Sofosbuvir/daclatasvir | 6 (0.5) | NA | 6 (0.4) | |
| Ledipasvir/sofosbuvir/ribavarin | 2 (0.2) | NA | 2 (0.1) | |
| Elbasvir/grazoprevir | 1 (< 0.1) | NA | 1 (< 0.1) | |
HCV = hepatitis C virus; NA = not applicable.
The pre–COVID-19 cohort had a therapy completion rate (Table 2) of 94.6% (N = 1,163) vs 89.1% (N = 244), (P = 0.001). Of the subset of patients who completed therapy (N = 1,407), the COVID-19 cohort was significantly less likely to have SVR laboratory tests collected (68.2% [N = 793] vs 59.0% [N = 144]; P = 0.006). In the subgroup of patients who completed therapy and had SVR laboratory tests collected (N = 937), there were no significant differences observed in the rate of patients who achieved SVR (98.0% [N = 777] vs 97.9% [N = 141]; P = 0.959). Taking the entire study population into account, patients were significantly more likely to obtain follow-up SVR laboratory tests in the pre–COVID-19 cohort compared with the post–COVID-19 cohort (66.9% [N = 823] vs 55.5% [N = 152], respectively; P < 0.001). Finally, the pre–COVID-19 cohort had a significantly higher confirmed SVR rate compared with the COVID-19 group (65.5% [N = 806] vs 53.6% [N = 147], respectively; P < 0.001).
TABLE 2.
Therapy Completion and SVR Rates
| Pre-COVID-19 | COVID-19 | Total | P value | ||
|---|---|---|---|---|---|
| Patients who completed therapy, n (%) | |||||
| N = 1,504 | Yes | 1,163 (94.6) | 244 (89.1) | 1,407 (93.6) | < 0.001 |
| No | 67 (5.4) | 30 (10.9) | 97 (6.4) | ||
| Patients who had final laboratory tests collected, n (%) | |||||
| N = 1,504 | Yes | 823 (66.9) | 152 (55.5) | 975 (64.8) | < 0.001 |
| No | 407 (33.1) | 122 (44.5) | 529 (35.2) | ||
| Patients who achieved SVR, n (%) | |||||
| N = 1,504 | Yes | 806 (65.5) | 147 (53.6) | 953 (63.4) | < 0.001 |
| Noa | 424 (34.5) | 127 (46.4) | 551 (36.6) | ||
| Subgroup: patients completing therapy | |||||
| Patients who had final laboratory tests collected, n (%) | |||||
| N = 1,407 | Yes | 793 (68.2) | 144 (59.0) | 937 (66.6) | < 0.001 |
| No | 370 (31.8) | 100 (41.0) | 470 (33.4) | ||
| Subgroup: patients completing therapy and collecting final laboratory tests | |||||
| Patients who achieved SVR, n (%) | |||||
| N = 937 | Yes | 777 (98.0) | 141 (97.9) | 918 (98.0) | 0.959 |
| No | 16 (2.0) | 3 (2.1) | 19 (2.0) | ||
a Includes patients who did not have final laboratory tests collected to evaluate SVR.
SVR = sustained virologic response.
Discussion
The COVID-19 group was significantly less likely to complete therapy, suggesting that telehealth encounters did not fully mitigate barriers to health care access presented by the COVID-19 pandemic. Similarly, SVR laboratory work was less likely to be completed by the COVID-19 cohort even when excluding differences in therapy completion rate. This suggests that allowing patients to receive laboratory services at locations external to our health-system did not increase laboratory adherence during the COVID-19 pandemic. This is in accordance with data presented from other health systems suggesting that rates of HCV-related laboratory testing decreased during the early days of the pandemic.14
We suspect that the observed difference in completion of therapy/laboratory assessments may be due to systemic barriers to access that were either worsened by or unique to the COVID-19 pandemic. Overall health care utilization volume decreased by approximately one-third in terms of provider visits and health care services performed on a global scale,15 suggesting increased barriers to access. Several barriers have been proposed, including diversion of health care resources and staff to treat COVID-19 cases, patient fear of exposure to COVID-19 reducing demand for health care, increases in the uninsured population due to rising unemployment, and an abrupt transition of care to a telehealth model.16,17 In addition to these barriers, patients with HCV have historically faced social barriers to health care because of an increased likelihood of having a lower socioeconomic status and low health literacy, as well as being more likely to be transient or reside in a rehabilitation facility. Other studies have noted that the COVID-19 pandemic has had an even greater negative effect on adherence to outpatient services in similarly vulnerable populations.18
For our patient population, we postulate that a worsening of preexisting barriers to health care utilization, increased patient hesitance toward health care interaction during a global pandemic, and ubiquitous patient interaction via telehealth may have impacted our decreased laboratory monitoring and therapy adherence in the post–COVID-19 cohort. A significant portion of our population of patients with HCV live in rural areas, and reliable access to internet services for telehealth services is not always guaranteed. However, patients who were able to follow-up with telehealth services expressed pleasure and appreciation for being able to be treated via telehealth and having medication mailed to them to alleviate the risk of COVID-19 exposure. We suspect that providing the option of telehealth vs in-person services to appropriate patients may still increase adherence when removed from the confounding factors of the COVID-19 pandemic. It is worth noting that of patients who did complete therapy and final laboratory tests in our study, differences in SVR were nonsignificant, suggesting that it was not quality of care but coordination of care during the pandemic that caused outcomes for our patients with HCV to be adversely affected.
LIMITATIONS
There are several limitations of this study. Because of the retrospective nature of this analysis, we are unable to draw concrete conclusions about which factors significantly influenced laboratory testing and medication adherence because of the influence of confounding factors. Additionally, we are limited in our ability to assess patients who may have finished therapy without returning to complete laboratory visits or contacting providers during the COVID-19 pandemic, as such data would be missing. Most glaringly, the pre–COVID-19 cohort is 4.5 times larger than the COVID-19 cohort. This is in part because of the disparity in the timelines for each group: the pre–COVID-19 cohort stretched over 27.5 months, whereas the COVID-19 cohort only spanned 8.5 months. As such, any outliers in the COVID-19 group have a greater impact on the overall results within that group.
Conclusions
During the COVID-19 pandemic, observed adherence to HCV DAA therapy and laboratory monitoring significantly decreased, as compared with prior months. During this time, therapy was complicated by the introduction of new barriers to health care access and a worsening of preexisting barriers to therapy. It is unclear whether health-system specialty pharmacy interventions to address pandemic barriers, including transitioning to entirely telehealth services and allowing patients to complete laboratory monitoring at external facilities, had any effect on the decrease in adherence. Further studies are needed to determine if offering a telehealth option for our patients separate from the confounding factors of the COVID-19 environment would offer any increases in access to care for patients with HCV.
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