Hepatitis C care cascade in HIV patients at an urban clinic in the early direct-acting antiviral era

Abstract

Guidelines advocate universal, prompt treatment of hepatitis C (HCV) infection in HIV/HCV co-infected patients, but barriers to uptake of HCV direct-acting antivirals (DAAs) remain unclear in this population. This retrospective study investigated the care cascade from HCV diagnosis to sustained virologic response (SVR) at an urban infectious disease clinic in Saint Louis, Missouri during the first 18 months of interferon-free DAA availability in the United States. Of 1949 HIV patients seen in clinic, 91.9% were screened for HCV and 5.4% (n = 106) had chronic HCV infection with follow-up. Of these 106 co-infected patients, 100 underwent fibrosis testing, 55 were offered DAAs, 38 completed treatment, and 37 achieved SVR. Delayed DAA treatment was associated with no insurance, substance abuse, poor HIV control, and younger age. Providers delayed DAA treatment most commonly for substance abuse, psychiatric disease, and uncontrolled HIV. Mean time to insurance decision from initial prescription was 20.9 ± 29.6 days and mean time to final decision was 29.9 ± 40.1 days. DAAs are highly successful in co-infected patients in this early period but insurance delays and misconceptions from the interferon era can ultimately limit uptake. Addressing these factors in a comprehensive treatment model may bridge disparities and improve real-world SVRs.

Keywords

Human immunodeficiency virus hepatitis C antiviral North America

Introduction

About 25% of patients with human immunodeficiency virus (HIV) in the United States and about 6% worldwide are co-infected with hepatitis C virus (HCV) with studies suggesting a six-fold higher odds of HCV infection in those with HIV compared to those without HIV.^1,2 HIV/HCV co-infection accelerates liver fibrosis, increases cirrhosis and hepatocellular carcinoma, and has higher healthcare utilization compared to HIV mono-infection.^3,4 Guidelines advocate universal HCV treatment in co-infected patients⁵ but uptake was low with interferon (IFN)-based therapy due to intolerability, contraindications, and low sustained viral response (SVR) rates (i.e., undetectable viral load at 12 weeks) of at best <14%.^6,7 The introduction of IFN-free direct-acting antiviral (DAA) therapies in 2014 revolutionized HCV treatment by improving tolerability and SVR rates.⁸ Treatment of co-infected individuals with DAAs is cost-effective,⁹ has high cure rates,¹⁰ and reduces liver morbidity and mortality.¹¹ Although DAA outcomes are similar between co-infected and HCV mono-infected patients in clinical trials, few studies have examined barriers to DAA uptake and HCV care in real-life co-infected populations.

Historically, HCV screening in HIV-infected populations was high but HCV treatment initiation was low.¹² Barriers to HCV treatment, referral, and uptake during the IFN-based era included race, drug side effects/interactions, substance use, inadequate care delivery infrastructure, medication cost, comorbid conditions (especially with psychiatric comorbidities), and lack of insurance.^12–14 Specific barriers to HCV treatment and SVR for co-infected patients in the early DAA era remain unclear. We conducted a retrospective care cascade analysis to clarify barriers to HCV treatment in an HIV/HCV co-infected population during the first 18 months of DAA availability in the United States.

Methods

Study design

We conducted a retrospective medical record review of all HIV-infected patients who were ≥18 years with active chronic HCV infection who obtained their care at the Washington University Infectious Disease (WUID) clinic in Saint Louis, Missouri from 1 January 2014 through 30 April 2016. Subjects were included if they had ≥1 follow-up visit during the study period and had chronic HCV infection, defined as detectable HCV RNA persisting for ≥6 months after an HCV antibody test. Patients were excluded if they cleared HCV spontaneously or from prior treatment. Subjects started on DAA therapy during this period were followed until completion of therapy and follow-up labs had been obtained.

The WUID clinic accepts Medicaid, Medicare, and select private insurance plans and is also funded in part by the Health Resources and Services Administration through the Ryan White C.A.R.E. Act Part C Early Intervention Services Grant program. HIV-infected patients without insurance were covered by the Ryan White Part C program and the AIDS Drug Assistance Program which only covered the cost of HIV treatment and did not cover DAAs. Missouri Medicaid (MO Healthnet) at the time of study did not have fibrosis requirements for co-infected patients (unlike for HCV mono-infected patients) but did have sobriety restrictions (no illicit drugs on testing for ≥3 months). Restrictions from other insurance providers varied but typically included fibrosis and sobriety requirements. Case managers, social workers, and pharmacists assisted patients with insurance, prescriptions, transportation, social hardships, and clinical appointments. Several experienced HIV providers managed chronic HCV infection working closely with a clinical pharmacist who assisted in DAA procurement and monitoring during and after therapy. While most DAAs were prescribed by the WUID clinic, some patients received DAAs through the Washington University Hepatology clinic or through research protocols conducted by the Washington University AIDS Clinical Trial Unit, part of the AIDS Clinical Trials Group funded by the National Institute of Allergy and Infectious Diseases. Care through these sites was performed in collaboration with the WUID clinic.

The study was approved by the Washington University Institutional Review Board and waiver of consent was approved.

Clinical data

Patients’ first available data during the study period were collected as baseline data including demographics, insurance information, comorbidities, and liver/renal chemistries. Each patient’s HIV status was characterized by their latest HIV viral load, CD4 cell count, and antiretroviral regimen before and after starting DAAs. HCV infection was characterized by HCV genotype and viral load, prior IFN-based treatment, and markers of liver disease severity from imaging, liver biopsy, or biomarker testing (e.g., Fibrosure). Imaging was only used to verify presence of cirrhosis and not for formal fibrosis staging, which was determined by liver biopsy and/or validated non-invasive measures such as Fibrosure/Fibrotest. Fibrosis staging modality was determined by insurance or prescription assistance program (PAP) requirements. Transient elastography, magnetic resonance elastography, and other measures of liver fibrosis were not available in the clinic at the time of study. Model for End-stage Liver disease (MELD) scores were calculated for all patients with cirrhosis as determined by previously mentioned markers of liver disease severity through standardized cutoffs and definitions.

We identified steps in our care cascade based on prior work on HCV mono-infected and HIV/HCV co-infected populations.^12,15 Clinical records were used to clarify decision-making on offering DAAs, defined as provider electing with the patient to move forward with treatment. Offering DAAs was chosen as an end-point to better characterize factors leading to treatment initiation as prior studies have shown greatest decline in the care cascade at referral and initiation steps. A clinical pharmacist performed most of the transactions related to DAA approval, including selection, assisting with prescription, insurance submission and appeals, and requesting PAP. For many patients, prescriptions were submitted to specialty care pharmacies with expertise in HIV and HCV care. If a DAA prescription was initially denied by insurance, prior authorization was attempted and if denied, an appeal submitted. Pharmaceutical PAPs were contacted if appeals were repeatedly denied. The dates of submission and final decision for all prior authorizations, appeals, and PAP applications were collected. Time to initial decision was defined as the difference in days from date of prescription submission to the date of initial decision from insurance (approval or denial). Time to final approval was defined as the difference in days from initial submission to insurance to final decision by insurance from prior authorization, appeal, and/or PAP approval.

Statistical analysis

Univariate analyses involved Chi square or Fisher’s exact tests for categorical variables and t- and Mann-Whitney tests for continuous variables. Logistic regression modeling with backwards selection was completed to identify predictors of offering DAA. All data were analyzed with IBM SPSS 20 statistical software (Armonk, New York, USA).

Results

Demographics and baseline characteristics

During the study period, a total of 1949 HIV patients were seen in the WUID clinic with 1791 (91.9%) screened for HCV, 215 (11.0%) with positive serum HCV antibody, and 106 (5.4%) had chronic HCV infection with ≥1 clinic visit for follow-up in the WUID clinic from 1 January 2014 to 30 April 2016. Table 1 summarizes the demographic characteristics of the 106 patients with chronic HCV infection. Chronically-infected patients had a median age of 52 years (IQR 46–56) and were predominantly male and African American. The most common comorbidities included psychiatric illness, hypertension, substance abuse, and chronic kidney disease. Four patients also had chronic hepatitis B viral infection. Thirty-one patients had cirrhosis though most had low MELD scores and low rates of decompensation. Seventy-six of the patients had suppressed HIV viral load for more than six months despite 105 being on combined anti-retroviral therapy (cART). Most patients had no prior IFN-based therapy and were infected with HCV genotype 1a.

Table 1.

Baseline demographic and clinical characteristics for HIV/HCV co-infected adults with follow up from Washington University Infectious Disease clinic from 1 January 2014 to 30 April 2016 (n = 106).

Variable	Result Median (IQR) or count (%)
Age (years)	52 (46.0–56.0)
Race/ethnicity
Black or African American	77 (72.6%)
White	29 (27.4%)
Gender
Female	18 (17.0%)
Male	88 (83.0%)
BMI	26 (22–29)
Insurance
Medicare	40 (37.7%)
Medicaid	28 (26.4%)
Medicaid and Medicare	0 (0.0%)
Private	30 (28.3%)
None	8 (7.6%)
More than one insurance	4 (3.8%)
Comorbid conditions
Hypertension	44 (41.5%)
Diabetes mellitus	10 (9.4%)
Psychiatric illness	58 (54.7%)
Chronic kidney disease (excluding dialysis)	21 (19.8%)
End-stage renal disease on dialysis	3 (2.8%)
Chronic HBV infection	4 (3.8%)
Active substance abuse^a	22 (20.8%)
Alcohol	10 (45.5%)
Amphetamines	1 (4.5%)
Cocaine	6 (27.3%)
Heroin/opiates	7 (31.8%)
Marijuana	5 (22.7%)
Tobacco	12 (54.5%)
Complications from liver disease
Ascites	4 (3.8%)
Encephalopathy	0
Cirrhosis	31 (29.2%), 1 with decompensated cirrhosis
Fibrosis testing^b	100 (94.3%)
Imaging for presence of cirrhosis	98 (92.5%)
Liver biopsy	29 (27.4%)
Fibrosure/Fibrotest	58 (54.7%)
MELD (n=31)	8 (7–10)
MELD ≤9	18 (58.1%)
MELD 10–19	12 (38.7%)
MELD 20–29	0 (0%)
MELD 30–39	1 (3.2%)
HIV characteristics
On cART	105 (99.1%)
CD4 cell count (cells/µL)	511.5 (289.5–636.3)
CD4 ≥350	72 (67.9%)
HIV viral load (copies/mL)	0.0 (0.0–24.3)
Suppressed HIV viral load >6 months	71 (67%)
cART regimen change for DAA	10 (9.4%)
HCV characteristics
Prior treatment with an IFN-based therapy	22 (20.8%)
Null response	9 (40.9%)
Partial response	2 (9.1%)
Relapse	4 (18.2%)
Intolerance to medication	4 (18.2%)
Unknown	3 (13.6%)
HCV genotype (n=106)
1a	71 (67.0%)
1b	19 (17.9%)
2	8 (7.5%)
3	3 (2.8%)
Unknown	5 (4.7%)
Log₁₀ HCV viral load (log₁₀ IU/mL)	6.4 (6.0–6.9)
Baseline laboratory results
Total bilirubin (mg/dL)	0.5 (0.4–0.7)
Serum albumin (g/L)	4.3 (4.1–4.4)
Serum ALT (units/L)	47.0 (30.8–81.5)
Serum AST (units/L)	47.5 (32.8–67.3)
Serum creatinine (mg/dL)	1.0 (0.9–1.2)
INR	1.0 (1.0–1.0)

DAA: direct-acting antiviral; INR: international normalized ratio; MELD: Model for End-stage Liver disease; IFN: interferon.

^aEach subject may have used more than one substance. Percentages are of total number of substance users (n = 22).

^bDenominators based on entire group of 106 subjects. Fibrosis testing modalities are not mutually exclusive. Liver biopsy and validated non-invasive methods such as Fibrosure/Fibrotest were considered formal fibrosis staging. Imaging was not used for staging but only used to determine if cirrhosis was present.

The care cascade of DAA in HIV/HCV co-infected individuals in the WUID clinic

In those with follow-up after diagnosis of chronic HCV infection, the greatest fall-off in the care cascade occurred at offering DAAs (Figure 1). In univariate analysis, offering DAAs was associated with older age, no substance abuse, better HIV control (longer suppression, lower HIV viral load, and higher CD4 cell count), and prior IFN-based treatment (Table 2). Providers most commonly cited active substance abuse, depression, and uncontrolled HIV for delay of DAA treatment (Table 3). Although 10 patients had their HIV cART regimen adjusted to accommodate DAA therapy, none were denied DAA therapy.

Figure 1.

The DAA care cascade of HIV/HCV co-infected patients in the Washington University Infectious Disease clinic from 1 January 2014 to 30 April 2016. A total of 1949 HIV patients were seen during this period with 1791 (91.9%) screened for HCV, 215 (11.0%) with positive HCV antibody, and 106 (5.4%) with chronic HCV infection.

Table 2.

Univariate analyses for factors related to offering DAA treatment.

Variable	Offered DAA Median (IQR) or count (%)
	Y (n=55)^a	N (n=51)	P
Demographics
Age (years)	54 (51–59)	50 (39–53)	<0.001
20<40 years	3 (5.5%)	13 (25.5%)	0.002
40<50 years	6 (10.9%)	11 (21.6%)
50<80 years	46 (83.6%)	27 (52.9%)
Any insurance^b	54 (98.2%)	44 (86.3%)	0.027
Medicaid	12 (22.2%)	16 (36.4%)	0.31
Medicare	24 (44.4%)	16 (36.4%)
Private	18 (33.3%)	12 (27.3%)
White/Caucasian	14 (25.5%)	15 (29.4%)	0.65
Black/African American	41 (74.5%)	36 (70.6%)	0.65
Male	45 (81.8%)	43 (84.3%)	0.73
Female	10 (18.2%)	8 (15.7%)	0.73
Comorbidities
Obesity (class I–III)	14 (25.5%)	7 (13.7%)	0.13
BMI	25 (21–30)	26 (23–28)	0.85
Hypertension	27 (49.1%)	17 (33.3%)	0.10
Diabetes mellitus	5 (9.1%)	5 (9.8%)	1.00
Psychiatric illness	29 (52.7%)	29 (56.9%)	0.67
Chronic kidney disease	11 (20%)	10 (19.6%)	0.96
Dialysis	0 (0%)	3 (5.9%)	0.11
Active substance abuse	3 (5.5%)	19 (37.3%)	<0.001
Liver-related factors
Cirrhosis	18 (32.7%)	13 (25.5%)	0.41
Ascites	3 (5.5%)	1 (2.0%)	0.62
Encephalopathy	0	0	–
Chronic hepatitis B infection	1 (1.8%)	3 (5.9%)	0.35
MELD	8 (7–11)	7 (7–10)	0.54
Any fibrosis testing	54 (98.2%)	46 (90.2%)	0.10
Imaging for presence of cirrhosis	53 (96.4%)	45 (88.2%)	0.15
Any fibrosis staging (biopsy or biomarker)	42 (76.4%)	25 (49.0%)	0.004
HIV-related factors
CD4 (cells/µL)	536 (360–676)	483 (224–605)	0.05
HIV viral load (copies/mL)	0 (0–0)	0 (0–530)	0.001
HIV suppressed >6 months	49 (89.1%)	22 (43.1%)	<0.001
HCV-related factors
HCV genotype 1	49 (89.1%)	41 (80.4%)	0.21
Log₁₀ HCV viral load	6.6 (6.0–7.0)	6.4 (6.0–6.9)	0.43
0<6 log₁₀	13 (23.6%)	15 (29.4%)	0.33
6<7 log₁₀	28 (50.9%)	29 (56.9%)
7<8 log₁₀	14 (25.5%)	7 (13.7%)
Prior IFN-based HCV treatment	17 (30.9%)	5 (9.8%)	0.007
Baseline lab values
Total bilirubin (mg/dL)	0.5 (0.4–0.7)	0.5 (0.3–0.6)	0.21
Albumin (g/L)	4.3 (4.1–4.5)	4.2 (4.0–4.4)	0.15
AST (units/L)	49 (36.0–64.0)	47 (32.0–91.0)	0.82
ALT (units/L)	46 (31.0–77.0)	50 (30.0–94.0)	0.47
Creatinine (mg/dL)	1.1 (0.9–1.3)	1.0 (0.8–1.2)	0.17
INR	1.0 (1.0–1.1)	1.0 (1.0–1.1)	0.66

DAA: direct-acting antiviral; INR: international normalized ratio; MELD: Model for End-stage Liver disease; IFN: interferon.

^aTwo patients who were offered DAA but declined are included.

^bThere are two separate Chi square tests when examining insurance: one for No vs. Any Insurance and one for Medicaid, Medicare, and Private Insurance. Denominators for Medicaid, Medicare, and Private Insurance are based on corresponding column counts for Any Insurance.

Table 3.

Reason for not pursuing DAA treatment (n = 53) as documented in the chart by providers.

Reason^a	Frequency	Percentage
Active substance abuse	19	35.8
Depression	12	22.2
Uncontrolled HIV	11	20.4
Other comorbid condition	7	13.0
Renal disease	3	5.6
Unclear based off chart	8	14.8
Patient not interested	2	3.8

^aThe listed reasons below are not mutually exclusive, so each patient may have multiple reasons for not pursuing DAA.

The multivariable logistic regression model for offering DAAs is shown in Table 4. Backwards stepwise modeling with a set of clinically or statistically significant predictors from univariate analyses was completed. Younger age (20–39 years) was associated with lower likelihood for DAA initiation. Suppressed HIV for >6 months was positively associated with offering DAAs while active substance abuse was negatively associated. HCV viral load, cirrhosis, psychiatric illness, and lack of insurance were not significantly associated with offering DAAs. In a separate covariate analysis for age, younger age (20–39 years) was associated with no insurance, no prior IFN-based treatment, HCV genotype 1, less cirrhosis, and poorer HIV control (Supplemental Table 1).

Table 4.

Multivariable logistic regression for factors related to offering DAA treatment.^a

Predictor	Odds ratio (95% CI)	P
Active substance abuse	0.1 (0.03–0.5)	0.003
HIV suppressed for >6 months	7.8 (2.6–23.7)	<0.001
Age		0.05
20–39 years	0.2 (0.04–0.9)	0.039
40–49 years	0.3 (0.09–1.3)	0.11
50–80 years (reference)	–	–

^aPredictors entered into initial model: age, log₁₀ HCV viral load, active substance abuse, HIV suppressed for >6 months, psychiatric illness, cirrhosis, prior IFN-based HCV treatment, any insurance.

Of the 53 patients who agreed to proceed with treatment, 40 were approved, 2 were denied, and 11 were still awaiting labs or studies (e.g., drug screens) before DAA prescription at the end of the study period. Of the 40 approved during the study period, 8 were approved on initial submission of the prescription, 30 required additional steps for approval, and 2 were obtained via clinical trials (Supplemental Figure 1). For the 11 patients awaiting evaluations, 7 subsequently received DAA treatment as of this report (mean 253.9 days ±206.9 days, range 47–626 days) and 4 patients have still not met all clinical and insurance requirements to start therapy due to ongoing drug use or failure to complete necessary evaluations. Decision times for the 38 prescriptions sent to pharmacy after initial application ranged from 0 to 124 days (mean 20.9 ± 29.6 days, median 8 days) and for final decision ranged from 0 to 129 days (mean time to final approval was 29.9 ± 40.1 days, median 8 days). Median time to both initial and final decisions for the four patients on Medicaid was 13 days (IQR 1.8–77.5 for both) compared to 8 days for both initial and final decisions for those not on Medicaid (IQR 3–30 days for initial decision, IQR 3–51.5 days for final decision).

Of the DAAs prescribed (n = 40), most were for ledipasvir/sofosbuvir (LED/SOF, n = 33) followed by sofosbuvir/ribavirin (SOF/RBV, n = 4), sofosbuvir/simeprivir (SOF/SIM, n = 2), and daclatasvir/sofosbuvir (DCV/SOF, n = 1). For those who initiated treatment (n = 40), 38 completed treatment, 1 was lost to follow-up, 1 discontinued treatment due to treatment-associated fatigue, and 37 completed ≥2 visits during the study and follow-up period. Of the 38 patients who completed treatment with a HCV viral load at 12 weeks or later, 37 had documented SVR and 1 patient, who was on DCV/SOF, failed to achieve SVR at the end of the study period (97.4% SVR in those treated) (Supplemental Table 2).

Discussion

Compared to IFN-based therapy, DAAs confer significantly higher SVR rates in co-infected individuals, but this population continues to have difficulties to access care. Similar to IFN-era studies where the greatest declines in care occurred at HCV treatment referral/initiation, our care cascade had its greatest loss at initiation of treatment. Given the potential for highly successful treatment in co-infected patients (completion and SVR rates of 95% and 97.3% in our study, respectively),¹⁶ it is crucial to understand factors related to offering DAAs. Our analysis suggested that barriers to offering treatment during the early DAA era largely fell under insurance and provider-related areas.

Insurance has been a significant barrier in prior studies to DAA uptake due to delays in decisions/appeals and the high cost of DAAs and HCV testing/staging.^17–20 In our study, time to initial and final insurance decisions were comparable to other cohorts studied at the time with multiple upfront denials before approval through the appeals process.^17,18 Although Medicaid status did not impact DAA insurance decision times in a clinically significant manner in our cohort, a recent study showed longer time to approval and evaluation for those on Tennessee Medicaid.¹⁸ Our small sample size precluded formal time to approval analysis. The differences in decision time in our study are likely due in part to differences in sample size and state Medicaid requirements for DAA payment at the time of study.²⁰

In our study, the greatest effects of insurance in the early DAA period on initiating treatment is unlikely related to decision times but likely more related to DAA cost and fibrosis/sobriety requirements as lack of insurance and substance abuse were associated with delayed initiation. Once insured, a patient’s insurance provider (including Medicaid) did not appear to affect the decision to initiate treatment. Substance use likely delayed the decision to offer DAAs at both insurance and provider levels. However, the full impact of insurance and how it affects provider decisions on offering DAAs is difficult to quantify with our small sample size.

Beyond impacting DAA initiation, insurance also has been associated with overall better care linkage and retention.^17–20 When compared to mono-infected populations at the time, our care retention rate was higher and similar to those in other co-infected populations.^15,21 Clinical pharmacists, case management, and social work support staff are key features of HIV clinics in the United States and may contribute to higher retention rates and navigation of complex insurance/PAP processes.^22,23 These support services are available to all our clinic patients regardless of insurance status. Without this support structure, co-infected patients would likely still have similar insurance barriers as other mono-infected cohorts. As DAA costs decrease and fibrosis work-ups simplify, insurance barriers will hopefully be significantly lessened, improving adherence to guideline-driven therapy.

In multivariable analysis, patients between 20 and 40 years old were less likely to be offered DAA treatment. This group had poorer HIV control, more active substance abuse, more often uninsured, and less cirrhosis. Younger age could be a surrogate for decreased urgency to treat based on overall lower disease burden, or related to perceived increased unreliability, lack of means, and risk for re-infection. Similar to IFN-era findings, providers in our study cited active substance abuse, uncontrolled HIV, and depression as the top reasons for delaying treatment.^12,24 Providers may have delayed treatment in active substance users due to concerns about HCV re-infection risk, decreased drug effectiveness, and insurance requirements for drug testing. Notably, there is no evidence to suggest treatment in drug users has decreased rates of completion and SVR.^20,25–27 Although poor HIV control is often associated with worse outcomes, psychiatric conditions are not exacerbated by DAA regimens like IFN-based regimens and should not deter DAA initiation.²⁸ Studies have shown other provider-level barriers including lack of knowledge of guidelines, omitting discussions about treatment, and blind assumptions that patients would prefer to defer treatment.²⁹ Ultimately, it is difficult to know which direction the association of these factors run with age, but provider perceptions on reliability, treatment effectiveness, and readiness can hinder DAA uptake if they are based on misconceptions and represent an area for education and improvement.

Given the current shortage of HCV providers and several studies showing effectiveness of non-specialists as DAA prescribers,^30–32 addressing provider perceptions and misconceptions is especially important to increase DAA uptake and bridge disparities. In the IFN-based era, provider perceptions on substance abuse, reliability, and psychiatric disease differed due to knowledge differences, level of exposure, and a reliance on other providers to give treatment.¹⁴ Despite achieving similar SVR outcomes as specialist providers (i.e., hepatology and infectious diseases physicians) in the DAA era, many non-specialists still have suboptimal knowledge about HCV treatment.³³ It is important to address these knowledge gaps and misconceptions to decrease costs, disease burden, and bridge disparities that can occur with treatment deferral.^34–37

As providers are only one link in the care cascade, coordinated approaches are needed to prioritize and allocate resources for better outcomes.^31,32 This has led many countries to form national plans such as those in Spain,³⁸ Netherlands,^39,40 France,⁴¹ European Union,⁴² Australia,^43,44 and United States.⁴⁵ In many of these countries, recent efforts for universal DAA access has improved treatment uptake and HCV incidence/prevalence, even in co-infected populations.^40,41,43 However, there often is a significant upfront cost while upscaling, which demonstrates the continued need for coordinated approaches to patients and resource allocation.⁴⁶ In 2016, the United States Veterans Administration (VA) prioritized funding for testing and treatment of all HCV-infected patients as part of a coordinated plan that included methods to address screening, prescribing capacity, linkage to care, treatment financing, and barriers to care (e.g., homelessness, substance use, mental health).⁴⁷ Our experience mirrors those of other co-infected cohorts and the VA that show improved linkage/retention due to the clinical pharmacists, case managers, and social workers that are already key parts of the HIV clinic infrastructure. These components provide more comprehensive assistance for insurance and individual factors such as homelessness, income, and substance abuse that are found more often in co-infected populations.⁴⁸ Other innovative approaches used at the VA and regionally include integrated substance use treatment, telemedicine, and shared electronic record systems for electronic consults that help reach high risk individuals, underserved areas, and expand linkage/retention in care.^30,47,49 Although not all aspects of the models used at the VA and other countries are transferrable to every health system, they reinforce the need for multifaceted and comprehensive approaches for better outcomes.

Strengths of this study include data generated from real-life experiences of providers and patients in an urban Ryan White-funded HIV clinic. Our clinic’s organization and services are similar to those of other Ryan White-funded clinics. Limitations include small sample size, inclusion of only one center, and retrospective nature of the study. We recognize these limit our multivariable analysis, prevent concurrent survey of provider attitudes/knowledge, and may decrease generalizability to other clinics with different infrastructure especially in insurance (e.g., differences by country and Medicaid state variations), available services, and patient characteristics. This study does not reflect any part of the care cascade prior to HIV clinic referral and after SVR. These limitations hinder our ability to conclude on the contribution of specific barriers to provider-related decisions, SVR, and reinfection risk which represent future areas of investigation.

In summary, DAAs are conferring HCV cure rates that are higher than ever in the co-infected population. However, many barriers still exist at patient, system, insurance, and provider levels. A multifaceted, comprehensive approach such as that found in HIV care clinics with a support team is needed to help with insurance difficulties and address individual factors to improve linkage/retention. Even with this approach, providers often are the limiting factor in treatment uptake. Proper education and funding are needed to fully realize more robust outcomes and bridge disparities in the co-infected population.

Supplemental Material

Supplemental material for Hepatitis C care cascade in HIV patients at an urban clinic in the early direct-acting antiviral era

Supplemental Material for Hepatitis C care cascade in HIV patients at an urban clinic in the early direct-acting antiviral era by Jimmy Ma, Lemuel Non, Surachai Amornsawadwattana, Margaret A Olsen, Alexandria Garavaglia Wilson and Rachel M Presti in International Journal of STD & AIDS

Footnotes

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 received no financial support for the research, authorship, and/or publication of this article.

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