Cost-Effectiveness of One-Time Hepatitis C Screening Strategies Among Adolescents and Young Adults in Primary Care Settings

Risk-based hepatitis C virus (HCV) testing is recommended for young adults. We used simulation modeling to show that routine rapid HCV testing during clinical visits might be cost-effective in settings with a high prevalence of HCV and injection drug use.

Abstract

Background

High hepatitis C virus (HCV) rates have been reported in young people who inject drugs (PWID). We evaluated the clinical benefit and cost-effectiveness of testing among youth seen in communities with a high overall number of reported HCV cases.

Methods

We developed a decision analytic model to project quality-adjusted life years (QALYs), costs (2016 US$), and incremental cost-effectiveness ratios (ICERs) of 9 strategies for 1-time testing among 15- to 30-year-olds seen at urban community health centers. Strategies differed in 3 ways: targeted vs routine testing, rapid finger stick vs standard venipuncture, and ordered by physician vs by counselor/tester using standing orders. We performed deterministic and probabilistic sensitivity analyses (PSA) to evaluate uncertainty.

Results

Compared to targeted risk-based testing (current standard of care), routine testing increased the lifetime medical cost by $80 and discounted QALYs by 0.0013 per person. Across all strategies, rapid testing provided higher QALYs at a lower cost per QALY gained and was always preferred. Counselor-initiated routine rapid testing was associated with an ICER of $71000/QALY gained. Results were sensitive to offer and result receipt rates. Counselor-initiated routine rapid testing was cost-effective (ICER <$100000/QALY) unless the prevalence of PWID was <0.59%, HCV prevalence among PWID was <16%, reinfection rate was >26 cases per 100 person-years, or reflex confirmatory testing followed all reactive venipuncture diagnostics. In PSA, routine rapid testing was the optimal strategy in 90% of simulations.

Conclusions

Routine rapid HCV testing among 15- to 30-year-olds may be cost-effective when the prevalence of PWID is >0.59%.

(See the Editorial Commentary by Chhatwal on pages 385–6.)

Currently, nearly all hepatitis C virus (HCV) transmission in the United States occurs among young persons who inject drugs (PWID) [1]. National guidance recommends therapy for infected PWID to prevent HCV transmission [2]. Similarly, the Institute of Medicine and the World Health Organization cite treatment for PWID as critical to elimination goals [3, 4]. Risk-based testing is recommended for PWID [5], and one-time testing is recommended for individuals born between 1945 and 1965 [6]. HCV screening among this birth cohort may delay the pending burden of liver disease but it does not address HCV transmission.

Experience from human immunodeficiency virus (HIV) testing suggests that healthcare providers are ineffective at identifying high-risk patients [7]. Routine testing may identify more cases; however, it requires testing a larger pool of individuals to identify 1 case. Standard venipuncture HCV antibody followed by confirmatory HCV RNA testing is the diagnostic gold standard, but this 2-test process limits linkage to care. In contrast, rapid point-of-care testing provides immediate initial results and could improve linkage to care. Finally, the best implementation model within primary care sites such as community health centers is unknown. One common approach is for physicians to initiate HCV testing orders. Another option is a dedicated counselor/tester with standing orders.

We used decision analysis to evaluate testing strategies among 15- to 30-year-olds at urban community health centers to answer the following questions: Should testing target PWID or should routine testing be implemented in areas with a high prevalence of HCV? What is the estimated prevalence of PWID at which routine testing should be favored? Should testing be performed using rapid or standard venipuncture testing? Should testing be offered by a physician during a routine outpatient visit or by a dedicated counselor/tester? Our findings provide projections of long-term costs, benefits, and cost-effectiveness and can inform local testing protocols and guidelines for testing.

METHODS

Analytic Overview

We used TreeAge Pro 2014 to develop a decision analytic model to evaluate the cost-effectiveness of HCV testing among 15- to 30-years-olds who do not already know their HCV status and are seen in primary care settings in community health centers (TreeAge Software, Inc., Williamstown, Massachusetts). We used the model to compare 9 strategies that differed in the following 3 ways (Table 1):

Table 1.

Strategies Considered

Test Type	Person Initiating the Test	Strategy
Standard venipuncture	Physician	Current practice
		Routine physician ordered, phlebotomist performed venipuncture testing
		Targeteda physician ordered, phlebotomist performed venipuncture testing
	Counselor/tester	Routine counselor initiated venipuncture testing
		Targeted counselor initiated venipuncture testing
Rapid	Physician	Routine physician initiated, counselor performed rapid testing
		Targeted physician initiated, counselor performed rapid testing
	Counselor/tester	Routine counselor initiated rapid testing
		Targeted counselor initiated rapid testing

^aProviders used a validated hepatitis C virus screening checklist.

• Approach to screening—Current practice vs expanded targeted risk-based screening vs routine screening. For current practice, testing was offered only to individuals perceived as high risk. The offer rate was based on data from 3 community health centers in Boston neighborhoods with a high number of reported HCV cases among 15- to 30-year-olds. In expanded targeted risk-based testing, we used a validated HCV screening checklist to identify high-risk individuals [8]. For routine testing, there was an attempt to approach all individuals regardless of perceived risk.

• Ordering provider—Physician vs. counselor/tester. When physicians ordered testing as part of routine visits, there were no additional costs beyond the test itself. In strategies involving counselor/testers, we included labor and HCV test costs [9, 10].

• Type of test—Rapid finger stick vs standard serum venipuncture. In rapid testing, pre- and post-test counseling was provided by a counselor/tester, and test results were available within 20 minutes. All rapid tests were US Food and Drug Administration approved, with high sensitivity and specificity. Venipuncture testing requires phlebotomy, and results are available in 2 to 3 days. A trained phlebotomist performed venipuncture testing ordered by a physician, while counselor/testers completed blood draws for the patients they tested. Patients with reactive tests are required to return to the clinic for RNA testing.

Model Structure

The model began with a decision analytic tree that simulated HCV testing at the community health center and the cascade of HCV care. The decision tree identified and categorized all patients at entry by HCV status. HCV-infected individuals were then assigned probabilities of linking to care. Final branches of the tree ended with a Monte Carlo simulation of the individuals’ remaining life expectancies based on their status at the beginning of the simulation. The lifetime simulation calculated lifetime costs and quality-adjusted life years (QALYs) [11, 12].

Decision Tree

Each strategy in the decision tree included the HCV cascade of care: test offer, result delivery, linkage to care, and confirmatory HCV RNA testing (Figure 1). Linkage to care was defined as a visit with a health provider for confirmatory testing.

Figure 1.

Decision analytic model schematic. Abbreviation: HCV, hepatitis C virus. Adapted from Schackman et al [12].

Monte Carlo Simulation

We adapted the hepatitis C cost-effectiveness model (HEP-CE) [12, 13] to simulate individuals’ lifetime progression with or without chronic HCV. HEP-CE is an individual-level state transition Monte Carlo simulation of HCV screening, linkage to care, and treatment. Following is an overview of the model.

HCV Disease Progression

The model assigned a METAVIR fibrosis stage at simulation start based on the patient’s age and presumed age at HCV infection [14]. Then, fibrosis progression was simulated as a series of probabilistic transitions. There was no HCV-attributable mortality or decrease in quality of life related to HCV until patients reached cirrhosis. Cirrhotic patients faced risks of liver-related death and decompensation events.

HCV Treatment

Only those who were tested, diagnosed, and linked to care were eligible for treatment. Genotype distribution was based on recent surveys of PWID, with higher prevalence of genotype 3 compared to the cohort born between 1945 and 1965 [15]. We used treatment with 8 to 12 weeks of sofosbuvir/ledipasvir for genotype 1 and with 12 weeks of sofosbuvir/velpatasvir for genotypes 2 and 3. When patients achieved sustained virologic response (SVR), costs attributable to HCV infection decreased by 50%, and quality of life returned to that of an age- and sex-matched person without infection. When patients with cirrhosis attained SVR, their liver-related mortality decreased by 94% [16]. Those who attained SVR, but continued to inject drugs, faced reinfection. We assumed potential for retreatment for individuals who were reinfected. Individuals who had cirrhosis at the time of HCV cure could still develop hepatocellular carcinoma.

Future HCV Screening and Linkage

Individuals who were not tested or who failed to link to care, as well as those who became reinfected, had a future opportunity to be identified and linked to care.

Model Data

Analyses

Strategies were compared using incremental cost-effectiveness ratios (ICERs), calculated as the additional cost divided by the additional health benefit of the next most costly strategy, and expressed as the cost per QALY gained [17]. We used the commonly cited US threshold of $100000/QALY. Strategies were defined as dominated if they were more costly and less effective than a competing strategy or if they were associated with an ICER greater than that of a more effective strategy. Outcome measures were assessed from a healthcare sector perspective, and QALYs and costs were discounted at 3% annually. Costs were in 2016 US dollars. We performed deterministic sensitivity analyses to identify parameters with the greatest impact on cost-effectiveness. We also conducted a sensitivity analysis in which confirmatory HCV RNA testing was automatically performed for reactive serology with venipuncture testing (“reflex RNA testing”). We then performed a probabilistic sensitivity analysis in which we defined key parameter values as distributions and used second-order Monte Carlo simulation to perform 100000 cohort simulations. We also calculated the additional number of individuals who need to be evaluated to identify a new HCV case when comparing routine to targeted testing and provided the incremental cost of testing from a clinic budgetary perspective.

Base Case Inputs

Clinical Data

Table 2 summarizes model inputs used for the base case analysis. Data obtained from the literature included background mortality rate, natural history of HCV infection, HCV prevalence, cascade-of-care inputs, test characteristics, treatment effectiveness, HCV-related mortality rate, and cost associated with testing, confirmatory testing, and treatment. We also modeled increased risk of death in PWID by using published standardized mortality ratios (SMRs) for PWID [18]. Throughout the simulation, individuals could transition between drug use states with appropriate adjustment to their SMR such that long-term cessation and relapse behavior influenced life expectancy [19].

Table 2.

Model Input Parameter

Variable	Base Case Value	Range Evaluated	Source
Cohort characteristics
Mean age, y	20	19–21	[24]
Proportion male	0.4	0.3–0.5	[24]
Baseline prevalence of PWID among 15- to 30-year-olds, %	1.2	0.6–12	[25, 26]
Average age at infection, y	19	15–30	[27]
Monthly probability of recovery from drug use	0.0139	0.0104–0.0174	[19]
Monthly probability of relapse to drug use	0.032	0.024–0.04	[19]
Baseline prevalence of HCV in young PWID, %	34	25–42	[28, 29]
HCV reinfection in young PWID, infections/100 person-years	15.6	1.9–26.7	[30]
Probability of clearing acute infection	0.26	0.19–0.32	[31, 32]
Proportion with genotype 1, %	55	41–69	[15]
Proportion with genotype 2, %	14	11–18	[15]
Proportion with genotype 3, %	31	23–39	[15]
Screening test approach
Screening test offer rate
Current practice:
PWID, %	5	4–6	[33]
Non-PWID, %	3	2–4	Assumption
Expanded risk-targeted approach:
Physician offer rate among PWID, %	20	15–25	[8]
Counselor offer rate among PWID, %	44	30–50	Assumption
Non-PWID, %	5	4–6	[8]
Routine approach, %
Physician offer rate	36	25–45	[10]
Counselor offer rate	80	60–99	[10]
Cascade of care variables
Proportion accepting screening offer, %	56	42–70	[33–35]
Proportion receiving screening test results, %
HCV standard serum antibody testing	74	56–93	[36, 37]
HCV rapid testing	99	74–99	[21]
Proportion identified with HCV and linked to care, %	53	40–66	[36, 38, 39]
10-year probability of re-engaging with care after being lost to follow-up, %a	27	20–34	Assumption; see footnote
HCV disease progression
Median time from infection to cirrhosis, y	25	19–31	[40]
Median time from cirrhosis to first decompensation, y	11	8–13	[41, 42]
Liver-related mortality with cirrhosis, deaths/100 person-years	3	2–3	[43]
HCV therapy efficacy
Genotype 1 without cirrhosis Probability of SVRb	0.98	0.74–0.99	[44, 45]
Genotype 1 with cirrhosis Probability of SVRb	0.97	0.73–0.99	[44, 45]
Genotype 2 without cirrhosis Probability of SVRb	0.99	0.74–0.99
Genotype 2 with cirrhosis Probability of SVRb	0.93	0.70–0.99	[46]
Genotype 3 without cirrhosis Probability of SVRb	0.98	0.74–0.99	[46]
Genotype 3 with cirrhosis Probability of SVRb	0.93	0.70–0.99	[46]
Costs
Select rapid testing program-related costsc
Counselor time, ( $)/hour	21	15–25	[47]
Rapid HCV antibody test, ($)/test	13	6–20	[12]
Routine medical costs per month without HCV,d ($)	142–1064	71–1596	[48]
Routine medical costs per month with HCV, no cirrhosis,d ($)	248	187–309	[48, 49]
Routine medical costs per month with HCV, mild to moderate cirrhosis,d ($)	446	319–557	[48, 49]
Routine medical costs per month with HCV, decompensated cirrhosis,d ($)	841	628–1064	[48, 49]
HCV therapy costs per month, ($)
Provider visit costs,e ($)	122	62–184	[9, 50]
Sofosbuvir/Ledipasvir	30400	15200–45600	[51]
Sofosbuvir/Velpatasvir	30400	15200–44600	Assumptionf [51]
Complete course genotype 1 infection (weighted average 8-week and 12-week), ($) No cirrhosis Cirrhosis	71950g 90190g	36480–108430 45600–135790	Assumption [9, 50, 51]
Complete course genotype 2 infection, ($) No cirrhosis Cirrhosis	137790 137820	68910–206730 68910–206730	Assumption [9, 50, 51]
Complete course genotype 3 infection, ($) No cirrhosis Cirrhosis	137820 137820	68910–206730 68910–206730	Assumption [9, 50, 51]
Managing treatment ending toxicity, ($)	240	120–370	[9, 50]
Quality of life
Without HCV infectionh	0.90	0.80–1.0	[52–54]
HCV with cirrhosis	0.62	0.55–0.75	[55–57]
HCV after first decompensation event	0.48	0.40–0.60	[55–57]
On HCV treatmenti	0.99	0.84–0.99	[58]
Major toxicity decrementj	0.16	0.09–0.25	[59]

Costs are in 2016 US dollars.

Abbreviations: HCV, hepatitis C Virus; PWID, person who injects drugs; SVR, sustained virologic response.

^aTen-year probability of re-engaging with care assumed to be half of original linkage probability.

^bProbability of SVR given reaching end of treatment.

^cSelect rapid testing program-related costs are presented in Table 2. Additional information is provided in Supplementary Table S1.

^dCosts varied as a function of age and sex.

^eTreatment visit costs are higher in the first month compared to other months.

^fAt the time of this analysis, the cost of velpatasvir was not available, and we made some assumptions on its likely cost.

^gWeighted average 8-week and 12-week.

^hThe less than 1.0 utility for those living without HCV infection reflects lower quality of life for individuals with HCV risk factors such as substance use.

ⁱThis utility was combined with an individual’s health state utility during the months that a patient was receiving HCV therapy without major toxicity. For example, a patient with HCV and mild to moderate fibrosis who underwent HCV treatment had a utility = 0.801 (0.90 × 0.89) during the months that (s)he was on medications.

^jThis utility “toll” was subtracted from a patient’s health state utility during the month of a major toxicity event.

As there was limited information for young adults during the interferon-free era, test acceptance, linkage to care, and treatment initiation were mostly derived from studies performed among PWID during the interferon era. For linkage to care rates, we included a recent study during the interferon-free era [20]. For strategies involving a counselor/tester, we used the offer rate reported in a randomized controlled trial of HIV testing in an emergency department as there was no comparable HCV-specific information [10].

Health-Related Quality of Life and Cost

Health outcomes were expressed in QALYs to incorporate mortality and morbidity associated with a particular health state (Table 2). We derived the direct medical costs of HCV care (clinic visits and monitoring of tests) by estimating healthcare utilization and applying unit costs. Estimates of time and labor costs for counselor/tester-initiated strategies were derived from a clinical trial [12, 21]. Treatment costs were derived from RedBook online. The costs of laboratory tests were from Medicare fee schedules.

RESULTS

Base Case

The average person lived for 79 years and accumulated $122080 in discounted lifetime medical costs (Table 3). As we were evaluating a screening intervention, the benefits were limited to the relatively small population of at-risk individuals (ie, PWID who are HCV infected). Although the population level average effects appeared to be small (0.0002–0.0013 incremental discounted QALYs, $10–80 incremental discounted cost), HCV-infected PWID who initiated therapy were projected to live approximately 2 years longer (50.18 vs 48.09 years) and accrued substantial additional discounted costs ($214000 vs $145000) compared with individuals who did not receive therapy.

Table 3.

Base Case Cost-Effectiveness Results

Strategy	Undiscounted Life Expectancy (y)	Total Discounted Cost per Person ($)	Remaining QALY per Person (QALY)	Incremental Cost- Effectiveness Ratio ($/QALY)
Current practice	79.0458	122080	23.7700	---
Physician-ordered, targeted venipuncture testing	79.0460	122090	23.7702	Dominated
Physician-ordered, counselor-performed targeted rapid testing	79.0461	122090	23.7702	40000
Counselor-initiated, targeted venipuncture testing	79.0465	122100	23.7705	Dominated
Physician-ordered, routine venipuncture testing	79.0463	122110	23.7704	Dominated
Counselor-initiated, targeted rapid testing	79.0467	122110	23.7706	44000
Physician ordered, counselor-performed routine rapid testing	79.0465	122110	23.7705	Dominated
Counselor-initiated, routine venipuncture testing	79.0471	122140	23.7709	Dominated
Counselor-initiated, routine rapid testing	79.0475	122160	23.7713	71000

Costs are rounded to the nearest $10, QALYs to nearest 0.0001, incremental cost-effectiveness ratios to nearest $1000/QALY. Small inconsistencies may be present due to rounding.

Abbreviation: QALY, quality adjusted life-year.

Rapid testing always provided greater life expectancy than venipuncture testing at either a lower lifetime medical cost or a lower cost/QALY gained. Thus, none of the venipuncture-based strategies were an efficient use of resources. Compared to physician-ordered targeted rapid testing, counselor/tester-initiated, targeted rapid testing provided an additional 0.0004 QALY at an incremental cost of $20 for an ICER of $44000/QALY gained. Compared to counselor/tester-initiated targeted rapid testing, counselor/tester-initiated routine rapid testing provided an additional 0.0006 QALY at an incremental cost of $40 for an ICER of $71000/QALY gained.

Compared to current practice, counselor-initiated routine rapid testing identified more cases (20% vs 5%) with a larger proportion of individuals reaching SVR (18% vs. 2%; Figure 2). Counselor-initiated routine rapid testing also reduced the proportion of deaths attributable to HCV (34% vs 31%) when compared to current practice. When comparing routine rapid to targeted testing performed by a counselor, an additional 464 individuals need to be evaluated in the clinic to identify 1 new HCV case. The incremental cost of testing to identify 1 case of HCV by routine testing compared to targeted testing was $8720.

Figure 2.

Outcomes for strategies that were not dominated. The bar graph shows the percentage of hepatitis C virus (HCV)-infected individuals who reached HCV cascade of care outcomes and the percentage of HCV-related deaths. Each bar represents a specific strategy. Abbreviation: HCV, hepatitis C virus.

Sensitivity Analysis

Deterministic Sensitivity Analysis

HCV and Injection Drug Use Prevalence

 Both the prevalence of PWID and the prevalence of HCV among PWID influenced cost-effectiveness results, but our overall conclusions did not change within a range of reasonable estimates for either prevalence value. For example, counselor-initiated routine rapid testing was the optimal strategy unless the prevalence of PWID among 15- to 30-year-olds was <0.59% (base case 1.2%; Figure 3) or the HCV prevalence among PWID was <16% (base case 34%).

Figure 3.

Incremental cost-effectiveness ratios (ICERs) of increased percentage of young people who inject drugs in the population. The line graph illustrates the ICER of the counselor-initiated routine rapid hepatitis C virus antibody testing compared to the next best alternative across a range of percentages of young people who inject drugs in the population. Abbreviations: ICER, incremental cost-effectiveness ratio; PWID, person who injects drugs; QALY, quality adjusted life-year; WTP, willingness-to-pay.

Testing Program Characteristics

 The cost-effectiveness of routine testing depended on the effectiveness of targeting testing to those at high risk. When we increased the probability that PWID aged 15 to 30 years were correctly identified and offered tests in the targeting strategies, routine testing became less attractive. However, only when targeted testing correctly identified at least 63% of PWID who were aged <30 years (base case 44%) did the ICER of routine rapid testing become >$100000/QALY. With this very effective targeting, counselor-initiated targeted rapid testing was the favored strategy with an associated ICER of $44000/QALY gained.

The cost-effectiveness of rapid testing compared to venipuncture depended on loss to follow-up before receiving rapid test results. When we decreased the proportion of result delivery for rapid screening from 99% (base case) to 75%, routine venipuncture testing initiated by a counselor/tester was the strategy that provided higher QALYs at a lower cost per QALY gained. The associated ICER was $82000/QALY gained.

Rates of Reinfection With HCV After Treatment and Post-Treatment Costs

 Compared to the base case of 15 cases per 100 person-years, a reinfection rate of 1.9 cases per 100 person-years yielded an ICER of $34000/QALY gained for routine rapid testing initiated by a counselor/tester. In contrast, a reinfection rate of 26.7 cases per 100 person-years was associated with an ICER of $104000/QALY gained. In addition, our conclusions were unchanged when we assumed that SVR resulted in a more substantial reduction in HCV-attributable cost.

Reflex HCV RNA Testing

 We evaluated a scenario in which confirmatory HCV RNA testing was automatically performed after reactive venipuncture testing. With reflex HCV RNA testing, routine testing was still the favorable approach, but venipuncture testing initiated by a counselor/tester provided higher QALYs at a lower cost per QALY gained (Supplementary Table S4).

Probabilistic Sensitivity Analysis

We performed 100000 simulations in which input values for offer rate, test results, test characteristics, treatment cost, treatment efficacy, and quality weights were varied simultaneously. We found that counselor/tester-initiated routine rapid testing was the optimal strategy in 90% of simulations, with counselor/tester-initiated targeted rapid screening preferred in the remaining 10%.

DISCUSSION

We demonstrate that routine HCV testing improved life expectancy and is cost-effective in 15- to 30-year-olds in primary care settings serving communities with a PWID prevalence exceeding 0.59%. This core finding was robust across broad ranges of loss to follow-up along the HCV cascade of care and the risk of HCV reinfection after cure. Our analysis shows that there is value in routinely testing 15- to 30-year-olds seen at health centers in areas with high reported cases of HCV, even with ongoing HCV testing in competing venues such as substance use treatment centers. This finding does not imply that testing at health centers should replace testing in other venues. Previous work demonstrates that testing in sites such as substance use treatment centers is cost-effective [12]. Given the frequency with which PWID access services in such nonmedical settings, these venues play a central role in any national strategy to eliminate HCV. Instead, we demonstrate that routine testing at health centers is an appealing approach to add to the portfolio of strategies for eliminating HCV. Fortunately, in the United States, it is possible to screen in multiple locations, and our findings demonstrate that it is cost-effective to do so. In light of high rates of HCV infection among young adults [22], our findings provide information to inform recommendations for HCV testing among persons aged 15–30 years.

Beyond the conclusion that “screening is cost-effective,” our analysis implies an ordered list of priorities for expanding testing in urban primary care settings. Our findings suggest that rapid testing should be considered instead of venipuncture diagnostics, or centers should ensure reflex RNA testing due to the reduction in loss to follow-up. Reflex RNA testing is not feasible in all settings, as it is associated with some logistical challenges. These include the possible risk of contamination if reflex testing uses the same tube collected for serology and the need to collect 2 tubes of blood upfront but only run RNA testing if the antibody is reactive.

In addition, centers in areas with high HCV case rates among those aged <30 years should consider using a dedicated counselor/tester to provide either targeted testing or routine testing to all. In our analysis, this strategy provides the best outcomes within commonly cited willingness-to-pay thresholds in the United States.

Despite our evidence that routine opt-out HCV testing using a dedicated counselor/tester is cost-effective, budgetary constraints may hinder implementation. Leveraging an existing HIV testing infrastructure with dedicated counselors/testers is a potential solution to reduce those costs and facilitate HCV testing expansion. Given that HIV and HCV share modes of transmission and HIV testing is recommended for all adults [23], this approach would use the existing infrastructure to increase HCV diagnosis.

It is also notable that routine testing remained cost-effective, even when we assumed very high incidence of HCV reinfection after HCV cure. Though perhaps counterintuitive, this finding reflects the reality that HCV therapy is itself cost-effective, with ICERs substantially below $1000000/QALY gained. Thus, as long as retreatment remains possible, screening continues to provide value. Essentially, each course of therapy is highly cost-effective and therefore allows for ratios to remain below the threshold. Although we found that screening remained cost-effective despite high rates of reinfection, preventing reinfection with harm reduction approaches could minimize reinfection rates.

There are limitations to our study. We do not currently have detailed information on current HCV testing rates for youth in primary care settings. We estimated our base case values by using rates of testing at 3 community health centers located in Boston neighborhoods with a high number of reported HCV cases. We then tested our assumptions in sensitivity analyses. Without information on the offer rate for rapid HCV testing compared to standard venipuncture testing, we used available information from HIV rapid testing. One might consider delaying testing until individuals are older to avoid possible reinfection. However, as demonstrated by our sensitivity analyses, conclusions remain robust despite very high rates of reinfection. Moreover, waiting until individuals reach older age would allow for ongoing HCV transmission. In addition, we only considered 1-time testing at age 15–30 years and did not evaluate strategies for repeat testing among those at high risk in this age range. Our analysis focused on strategies to find undiagnosed HCV cases by current guidance. Periodic, or repeat, testing is also important but it is intended to improve outcomes among a different population—individuals who are already known to be at high risk. We also did not include the influence of extrahepatic manifestations independent of fibrosis stage such as vasculitis or lymphomas.

We show that routine testing provides the most clinical benefit and best economic value in an urban community health setting where HCV prevalence is high. Centers should consider either routine rapid testing by a counselor/tester or provide reflex HCV RNA following venipuncture testing. Future studies are needed to define the programmatic effectiveness of HCV treatment among youth and the testing and treatment acceptability in this population.

Supplementary Data

Supplementary materials are available at Clinical Infectious Diseases online. Consisting of data provided by the authors to benefit the reader, the posted materials are not copyedited and are the sole responsibility of the authors, so questions or comments should be addressed to the corresponding author.

Notes

Disclaimer. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.

Financial support. This project was supported by grants from the National Institute on Drug Abuse (R01DA031059, R01DA031059-03S1, P30DA040500, R25DA035163) and the National Institute of Allergy and Infectious Diseases (P30AI042853).

Potential conflicts of interest. All authors: No reported conflicts of interest. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed.