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The cost-effectiveness of improved hepatitis C virus therapies in HIV/hepatitis C virus coinfected patients

Linas, Benjamin P.a,b; Barter, Devra M.a; Leff, Jared A.c; DiLorenzo, Madelined,e; Schackman, Bruce R.c; Horsburgh, Charles R.a,b; Assoumou, Sabrina A.a; Salomon, Joshua A.f; Weinstein, Milton C.g; Kim, Arthur Y.e; Freedberg, Kenneth A.b,d,e,g

doi: 10.1097/QAD.0000000000000093
Clinical Science

Objectives: To evaluate the effectiveness and cost–effectiveness of strategies to treat hepatitis C virus (HCV) in HIV/HCV coinfected patients in the United States.

Participants: Simulated cohort of HIV/HCV genotype 1 coinfected, noncirrhotic, HCV treatment-naive individuals enrolled in US HIV guideline-concordant care.

Design/interventions: Monte Carlo simulation comparing five strategies: no treatment; dual therapy with pegylated-interferon (PEG) and ribavirin (RBV); ‘PEG/RBV trial’ in which all patients initiate dual therapy and switch to triple therapy upon failure; ‘IL28B triage’ in which patients initiate either dual therapy or triple therapy based on their IL28B allele type; and PEG/RBV and telaprevir (TPV) triple therapy. Sensitivity analyses varied efficacies and costs and included a scenario with interferon (IFN)-free therapy.

Main measures: Sustained virologic response (SVR), life expectancy, discounted quality-adjusted life expectancy (QALE), lifetime medical costs, and incremental cost-effectiveness ratios (ICERs) in $/quality-adjusted life years (QALY) gained.

Results: ‘PEG/RBV trial,’ ‘IL28B triage,’ and ‘triple therapy’ each provided 72% SVR and extended QALE compared with ‘dual therapy’ by 1.12, 1.14, and 1.15 QALY, respectively. The ICER of ‘PEG/RBV trial’ compared with ‘dual therapy’ was $37 500/QALY. ‘IL28B triage’ and ‘triple therapy’ provided little benefit compared with ‘PEG/RBV trial,’ and both had ICERs exceeding $300 000/QALY. In sensitivity analyses, IFN-free treatment attaining 90% SVR had an ICER less than $100 000/QALY compared with ‘PEG/RBV trial’ when its cost was $109 000 or less (125% of the cost of PEG/RBV/TVR).

Conclusion: HCV protease inhibitors are most efficiently used in HIV/HCV coinfection after a trial of PEG/RBV, sparing protease inhibitors for those who attain rapid virologic response and SVR. The cost-effectiveness of IFN-free regimens for HIV/HCV coinfection will depend on the cost of these therapies.

Supplemental Digital Content is available in the text

aSection of Infectious Diseases, Department of Medicine, Boston Medical Center

bDepartment of Epidemiology, Boston University School of Public Health, Boston, Massachusetts

cDepartment of Public Health, Weill Cornell Medical College, New York, New York

dDivision of General Medicine, Massachusetts General Hospital

eDivision of Infectious Diseases, Massachusetts General Hospital

fDepartment of Global Health and Population

gDepartment of Health Policy and Management, Harvard School of Public Health, Boston, Massachusetts, USA.

Correspondence to Benjamin P. Linas, MD, MPH, HIV Epidemiology and Outcomes Research Unit, Boston Medical Center, 850 Harrison Avenue, Dowling-3N Room 3205, Boston, MA 02118, USA. Tel: +1 617 414 5238; fax: +1 617 414 7062; e-mail:

Received 13 August, 2013

Revised 19 September, 2013

Accepted 19 September, 2013

Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal's Website (

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Hepatitis C virus (HCV) coinfection is a leading cause of morbidity and mortality among HIV-infected individuals [1]. Newer HCV therapies utilizing HCV protease inhibitors were licensed for the treatment of HCV monoinfection in the United States and Europe in 2011 [2]. Phase 2 clinical trials in HIV/HCV coinfected patients demonstrate sustained virologic response rates as high as 74% in those with HCV genotype 1 infection [3,4]. Clinical trial results for oral interferon (IFN)-free regimens for HCV monoinfected patients have been presented at national conferences, and the first IFN-free regimen for the treatment of HCV genotypes 2 and 3 in HCV monoinfected patients was submitted to the US Food and Drug Administration (FDA) in April 2013 [5]. These regimens attain 90% or greater SVR, with little toxicity and only 12 weeks of therapy [6–9].

The improved efficacy and toxicity profiles of new treatments are accompanied by higher costs [1,10,11]. Because many HIV/HCV coinfected patients rely on publicly funded health insurance (or other public payers such as the prison healthcare system), treatment for HIV/HCV coinfection often occurs in resource-constrained settings [12]. In such environments, efficient use of HCV therapy could increase the number of people treated for HCV, maximizing the population-level benefits of HCV treatment.

Genome-wide association studies have discovered that those with homozygosity at a single nucleotide polymorphism (rs12979860) related to the interleukin-28 beta subunit (IL28B) gene, the ‘CC’ genotype, have better treatment response to pegylated interferon (PEG) and ribavirin (RBV) than those with non-CC genotypes [13–16]. Using IL28B to triage CC genotype patients to initiate PEG/RBV without an HCV protease inhibitor could control costs. Another potential strategy is to initiate all patients on PEG/RBV, adding an HCV protease inhibitor only for those who experience virologic failure. The comparative effectiveness and cost–effectiveness of such approaches in HIV/HCV coinfection are unknown.

To inform strategies for use of new therapies for HIV/HCV coinfected patients, we investigated the cost–effectiveness of alternative treatment options and identified approaches that would efficiently use scarce budgetary resources, potentially expanding access to HCV treatment.

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Analytic overview

We used the Hepatitis C Cost-Effectiveness (HEP-CE) model, a Monte Carlo simulation of screening and treatment of HCV, to estimate the effectiveness and cost–effectiveness of strategies for treating HIV/HCV coinfection. The model is summarized below and details are available elsewhere [17] and in the supplemental materials, We considered five HCV treatment strategies (Fig. 1) [18]:

  1. No treatment
  2. ‘Dual therapy’ – 48 weeks of response-guided PEG/RBV.
  3. ‘PEG/RBV trial’ – 48 weeks of response-guided PEG/RBV. Individuals who fail PEG/RBV at any time during therapy advance to triple therapy (strategy 5).
  4. ‘IL28B triage’ – individuals are triaged to commence either PEG/RBV or triple therapy (strategy 5) based on IL28B genotype. Those with ‘CC’ alleles initiate PEG/RBV, whereas all others start triple therapy. Patients who fail PEG/RBV advance to triple therapy.
  5. ‘Triple therapy’ – treatment with 48 weeks of PEG/RBV in combination with the HCV protease inhibitor telaprevir (TVR).
Fig. 1

Fig. 1

All analyses simulated a cohort of 10 million hypothetical HIV/HCV coinfected individuals chronically infected with HCV genotype 1, noncirrhotic, HCV treatment-naive, and enrolled in US HIV guideline-concordant care. As per these guidelines, individuals were either on suppressive antiretroviral therapy (ART) or were HIV treatment-naive with CD4+ cell count more than 500 cells/μl (Table 1) [1,3,6,7,14,16,19–84].

Table 1-a

Table 1-a

Table 1-b

Table 1-b

We projected outcomes including the percentage attaining SVR, life expectancy, discounted quality-adjusted life expectancy (QALE), discounted lifetime medical costs, and the incremental cost–effectiveness ratio (ICER) of each strategy compared to its next costliest alternative. We conducted one-way and multiway sensitivity analyses on these results.

We also considered scenarios using an oral, IFN-free regimen that was more effective and less toxic than PEG/RBV/TVR. We considered a range of IFN-free regimen efficacies and costs, and we identified cost/efficacy combinations leading to IFN-free therapy having an ICER less than $100 000/quality-adjusted life year (QALY) when compared with the preferred treatment strategy without an IFN-free regimen. To explore cost-reducing strategies in cost-constrained environments, we considered scenarios similar to the base case in which patients initiate a trial of PEG/RBV, but instead of switching to triple therapy upon a failed course of PEG/RBV, they switch to IFN-free therapy.

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Model structure

Hepatitis C virus disease progression

The model simulates HCV disease progression through three stages of liver disease: mild-to-moderate fibrosis, cirrhosis, and decompensated cirrhosis. Consistent with previous studies, all disease stages of HCV infection are associated with increased resource utilization and decreased quality of life (QoL) [19–21,85–88]. When individuals become cirrhotic, they are subject to increased mortality attributable to liver disease [22,23]. With successful treatment (SVR), HCV-related mortality, resource utilization, and QoL revert to those of HIV monoinfected individuals.

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HIV disease progression

We used the Cost-Effectiveness of Preventing AIDS Complications (CEPAC) model to estimate the cohort's HIV-related outcomes and costs [24]. CEPAC simulates HIV disease progression through CD4+ cell count and HIV RNA levels. We used the CEPAC model to assess the cohort's progression of HIV disease across a range of CD4+ cell and viral load categories. CEPAC provided sex-stratified estimates of monthly HIV-related mortality conditional upon being alive at the beginning of the month (life table), mean monthly medical costs related to HIV disease, and QoL related to HIV infection. We used these CEPAC outputs as HEP-CE model inputs, such that in every month, individuals in the HEP-CE model were exposed to sex and time-dependent HIV-attributable mortality, costs, and QoL changes (see supplemental materials,

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Hepatitis C virus therapy

‘Dual therapy’

All individuals initiate a planned 48-week course of weekly PEG alfa-2a 180 μg subcutaneously in combination with twice daily oral RBV 600 mg (average cohort weight 80 kg). Simulated patients undergo routine HCV RNA testing at the end of treatment week 4. Those with detectable viremia stop HCV therapy, whereas those with suppressed HCV RNA (rapid virologic response – RVR) continue a planned 48-week treatment course [3].

While taking HCV medications, all patients experience a monthly QoL decrement related to adverse therapy symptoms. Additionally, a proportion of patients on therapy experience nontreatment ending toxicities, including moderate anemia managed by RBV dose reduction and moderate neutropenia managed with PEG dose reduction and twice weekly filgrastim 300 μg subcutaneously. Patients with nontreatment ending toxicities accrue cost adjustments related to dosing changes and additional therapies, but they remain on HCV treatment and are eligible to attain SVR. In every month, patients also risk treatment discontinuation due to nonadherence or major toxicity, including severe anemia or rash. Major toxicity is associated with additional costs and an additional QoL decrement.

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‘Pegylated interferon/ribavirin trial’

All patients initiate the same PEG/RBV regimen as in the ‘dual therapy’ strategy. Those who fail to attain virologic suppression at week 4 (RVR) subsequently add TVR to their regimen for 12 weeks as described below (‘triple therapy’). Patients who attain RVR on PEG/RBV at week 4, but do not achieve SVR at treatment completion, are re-treated with PEG/RBV/TVR. Patients who stop PEG/RBV therapy due to nonadherence or major toxicity are ineligible to advance to PEG/RBV/TVR.

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‘Interleukin-28 beta subunit triage’

IL28B genotyping is used to triage patients to start either PEG/RBV (CC genotype), or PEG/RBV/TVR (non-CC genotypes). The approach to modeling PEG/RBV therapy and the addition of TVR to failing regimens is the same as that for ‘PEG/RBV trial.’

The efficacy of protease-based therapy among those who fail PEG/RBV is lower than its efficacy as first-line therapy [25]. Exposure to PEG/RBV, however, does not compromise protease efficacy if the individual simply started treatment with PEG/RBV/TVR [25]. We therefore assume that nonresponders to PEG/RBV are more likely to be nonresponders to PEG/RBV/TVR when retreated in all strategies, and we assume that in the ‘PEG/RV trial’ strategy, exposure of patients to PEG/RBV before adding a protease inhibitor does not reduce the overall percentage of the cohort who ultimately attain SVR.

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‘Triple therapy’

All patients initiate a regimen of PEG/RBV/TVR for 12 weeks followed by 36 weeks of PEG/RBV alone for a 48-week total therapy course. Patients receive 750 mg three times daily of TVR in combination with the same dosage of PEG/RBV as described above. Patients undergo routine HCV RNA monitoring at treatment weeks 4 and 12. Those with HCV RNA more than 1000 copies/ml at either time point stop therapy. We did not specifically model TVR dose increases required when using efavirenz, but we effectively included such dose changes in drug cost sensitivity analyses. The approach to modeling adherence, toxicity, and therapy disutility was the same as for dual therapy, but we included rash as potential treatment toxicity.

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Interferon-free regimen’

Patients initiate a 12-week course of an HCV protease inhibitor, a polymerase inhibitor, and RBV [6,7,26]. Compared with IFN-containing regimens, this interferon-free regimen yields lower toxicity, higher treatment adherence, higher QoL while on therapy, and higher SVR rates. Individuals face a risk of treatment ending toxicity and nonadherence, but we assumed there are no early stopping criteria for IFN-free therapy.

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We assessed costs in the model from the health system perspective. In each simulation month, individuals accrue ‘background costs’ associated with non-HIV/HCV-related healthcare. In addition to these costs, there are HCV-specific and HIV-specific costs. HCV-associated costs include those of HCV medications, physician visits, laboratory tests for monitoring and safety, emergency department visits, and hospitalizations for liver-related events (Table 1). HIV-associated costs include costs of ART, laboratory monitoring, and hospital admissions associated with AIDS-related events [27–35].

To reflect increased resource utilization among those with HIV/HCV coinfection compared with HIV monoinfection, all costs except those of HIV and HCV medications and HIV-related testing are 70% greater in coinfected individuals than in HIV monoinfected individuals [19,36].

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Quality of life

QoL estimates include independent effects related to HIV and HCV infection integrated in the model using a multiplicative assumption [20,21,37–40]. HIV-related QoL is a function of current CD4+ cell count and acute AIDS-related events. HCV-related QoL is a function of fibrosis stage, HCV treatment status, and treatment-related toxicity (Table 1).

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Base case parameters

The cohort was 66% male [41–44], mean age 45 years (SD 6 years) [41–45], mean CD4+ cell count 520/μl (SD 100/μl) [46–48], and 32% IL28B CC genotype prevalent [14] (Table 1). The median time to cirrhosis from HCV infection (mean age of infection 26 years [49]) was 25 years [50], and the rate of liver-related deaths with cirrhosis was 2.73 per 100 person-years [22,23].

The total SVR probability for PEG/RBV among those with CC genotype was 55% [16,51–54] and 20% for CT or TT [16,51–53]. The total SVR probability with PEG/RBV/TVR was 74% [3] and ranged from 80 to 100% with an IFN-free regimen [6,7]. The probability of withdrawal due to toxicity or nonadherence was 11% for triple therapy [3], 23% for dual therapy [54], and 3% for IFN-free therapy [6,7]. The cost of a complete course of dual and triple therapy, including the cost of managing toxicities, was $43 000 and $87 300 respectively. The cost of a complete course of IFN-free therapy ranged from $87 300 to $175 000 [28,30]. Those with mild-to-moderate fibrosis, cirrhosis, and decompensated cirrhosis had a QoL of 0.89, 0.62, and 0.48, respectively [20,21,40].

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We calculated the ICER of each treatment strategy as the additional cost divided by the additional QALY gained compared with the next less expensive strategy [89,90]. Strategies were considered inefficient and excluded from ICER calculations if they resulted in higher costs but fewer QALYs gained or had a higher ICER than a more effective strategy [90,91]. QALYs and costs were both discounted at 3% annually [90]. We assumed a societal willingness-to-pay of $100 000 per QALY in which strategies below the threshold were considered ‘cost-effective’ [92,93].

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Base case

Without HCV treatment, undiscounted life expectancy was 13.24 years, QALE was 6.76 QALYs, and discounted lifetime medical costs were $198 700 (Table 2). ‘Dual therapy’ yielded 30.8% attaining SVR, increased life expectancy by 0.52 to 13.76 years, QALE by 0.84 to 7.60 QALY, and lifetime medical costs by $23 200 to $221 900. The ICER for treating patients with dual therapy compared with no treatment was $27 700/QALY gained.

Table 2

Table 2

The ‘PEG/RBV trial’ strategy was the least costly approach to using an HCV protease inhibitor. ‘PEG/RBV trial’ increased SVR to 72% and life expectancy and QALE compared with ‘dual therapy’ by 0.70 years and 1.13 QALY, a larger gain than that provided by ‘dual therapy’ compared with ‘no treatment.’ ‘PEG/RBV trial’ increased lifetime medical cost compared with ‘dual therapy’ by $42300 to $264 200, resulting in an ICER for ‘PEG/RBV trial’ compared with ‘dual therapy’ of $37 500/QALY.

The ‘IL28B triage’ and ‘triple therapy’ scenarios both increased SVR by less than 1% compared with ‘PEG/RBV trial.’ As a result, life expectancy and QALE increased by less than 0.01 QALY, resulting in ICERs more than $300 000/QALY (Table 2).

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Sensitivity analysis

‘PEG/RBV trial’ remained the preferred (<$100 000/QALY) treatment strategy when we varied treatment efficacy for both PEG/RBV and PEG/RBV/TVR regimens. Across all efficacy assumptions, the ICERs of ‘IL28B triage’ compared with ‘PEG/RBV trial’ and of ‘triple therapy’ compared with ‘IL28B triage’ remained more than $250 000/QALY.

Total treatment costs had the greatest impact on cost–effectiveness conclusions (Fig. 2). With a higher cost of PEG/RBV therapy, the ‘PEG/RBV trial’ and ‘dual therapy’ strategies became less efficient than ‘IL28B triage’. With higher PEG/RBV costs, ‘triple therapy’ remained economically unattractive with an ICER more than $500 000/QALY.

Fig. 2

Fig. 2

When we reduced the cost of PEG/RBV/TVR by 50%, the ‘triple therapy’ strategy was most efficient, with an ICER compared to no treatment of $20 500/QALY. This remained the preferred strategy at a threshold of $100 000/QALY as long as the cost of PEG/RBV/TVR was less than $50 000 (57% of base case cost). When we increased the cost of PEG/RBV/TVR by 50%, the ‘PEG/RBV trial’ strategy was preferred with an ICER of $55 600/QALY compared with ‘dual therapy’.

‘PEG/RBV trial’ remained the preferred treatment strategy with an ICER less than $100 000/QALY across a broad range of other sensitivity analyses including HIV therapy efficacy, time to cirrhosis, QoL, and costs of routine medical care, ARTs, and laboratory tests (Fig. 2).

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Interferon-free scenario

Treating individuals with an ‘IFN-free’ regimen achieving 90% SVR extended discounted QALE by 2.56 years compared with no treatment, by 0.59 years compared with ‘PEG/RBV trial’, and by 0.57 years compared with ‘triple therapy’. In a two-way sensitivity analysis comparing ‘IFN-free’ therapy to ‘PEG/RBV trial’, an IFN-free regimen that provided a 90% SVR rate had an ICER less than $100 000/QALY when the cost of the IFN-free regimen was 125% or less of the cost of a complete course of PEG/RBV/TVR, or approximately $109 000 (Fig. 3). An IFN-free regimen that attained 95% SVR had an ICER less than $100 000/QALY when the cost of the IFN-free regimen was 150% or less of the cost of a complete course of PEG/RBV/TVR, or $131 000.

Fig. 3

Fig. 3

When we considered potential intermediate strategies using IFN-free therapy, a strategy in which all patients initiated PEG/RBV and only those with treatment failure advanced to an IFN-free regimen, was preferred with an ICER compared with ‘dual therapy’ of $51 800/QALY (Supplemental Table 4, In this scenario, providing IFN-free therapy to all patients was cost-effective (ICER <$100 000/QALY) only when the cost of a course of IFN-free treatment was less than $88 000 (base case $131 000), or when the QoL of being on PEG/RBV was less than 0.3 (similar to having compensated cirrhosis).

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We assessed the cost-effectiveness of new therapies to treat HIV/HCV genotype 1 coinfected individuals and found that although new HCV therapies improve life expectancy in coinfected patients, they substantially increase costs and are most efficiently used after an initial trial of PEG/RBV to determine protease inhibitor necessity. Furthermore, the economic efficiency of future IFN-free regimens will depend greatly on their cost. In highly cost-constrained environments, initiating treatment with PEG/RBV, or using IL28B genotyping to triage patients to IFN-free therapy, may be economically attractive.

It is not surprising that we found that initiating all patients on ‘triple therapy’ is not cost-effective. The Re-treatment of Patients with Telaprevir-based Regimen to Optimize Outcomes (REALIZE) study demonstrates that using a lead-in of PEG/RBV before adding TVR is efficacious and does not compromise overall SVR [25]. Extrapolating this finding to naive patients, in HIV/HCV coinfected patients, there is little disadvantage to the ‘PEG/RBV trial’ approach, as patients who do not attain RVR with PEG/RBV alone can add TVR to their regimen without extending the treatment course or decreasing treatment efficacy. Those who attain RVR with PEG/RBV have over a 95% chance of ultimately attaining SVR [54,94].

Several important observations explain the greater economic efficiency of the ‘PEG/RBV trial’ strategy compared with ‘IL28B triage’. First, the efficacy of PEG/RBV in non-CC genotypes is approximately 20%; thus, the ‘IL28B triage’ strategy forgoes substantial cost savings without additional clinical benefits when it assigns the 20% of patients who would have attained SVR on PEG/RBV instead to triple therapy. Second, the negative predictive value of failing to attain RVR as a predictor of attaining SVR is approximately 98% [54,94], whereas that of IL28B CC is only 80% [95–97]. Therefore, the ‘PEG/RBV trial’ strategy functions as a more specific ‘diagnostic test’ than IL28B testing to prioritize patients to triple therapy.

A cost–effectiveness analysis in HCV monoinfection has reported that protease inhibitor-based therapy for all HCV monoinfected patients is cost-effective when compared with the ‘IL28B triage’ strategy [18]. In the base case analysis, however, that study did not consider retreatment with a protease-based regimen for patients who were triaged to PEG/RBV. When the authors did consider re-treatment, the ICER of ‘triple therapy’ was approximately $100 000/QALY, and for some subgroups, IL28B-triage was a dominant strategy. A critical difference between HCV monoinfection and coinfection is that in monoinfection, the overall treatment course of protease-based therapy is usually 6 months, whereas that of coinfection is 12 months. As a result, strategies that assign some monoinfected patients to initiate PEG/RBV have a greater negative impact on QoL. Simultaneously, protease-based regimens are relatively less costly because using a protease inhibitor often saves the expense of 6 additional months of PEG/RBV. Thus, there may be greater disadvantage of the ‘PEG/RBV trial’ approach in HCV monoinfection than in HIV/HCV coinfection, in which response-guided therapy to shorten therapy is not yet proven. Finally, even in HCV monoinfection, the cost-effectiveness of initiating all patients on triple therapy is not entirely clear, as at least one cost-effectiveness analysis has found that ‘IL28B-triage’ is preferred [98].

In two-way sensitivity analysis, we demonstrated the range of costs and efficacies across which future IFN-free regimens would be cost-effective compared with the ‘PEG/RBV trial’ approach using TVR. We found that total therapy costs remained the critical factor determining cost-effectiveness. Assuming an IFN-free regimen that attains 90% SVR, treating all patients with IFN-free therapy will be cost-effective compared with protease-based regimens only if the IFN-free regimen costs are approximately $109 000 or less.

We also explored strategies to reduce the cost of IFN-free therapy by triaging such medications to a proportion of the population. In that case, initiating PEG/RBV and advancing to IFN-free treatment for failure was the preferred strategy. Importantly, a trial of PEG/RBV was cost-effective despite the fact that in the base case scenario, QoL while taking therapy was 10 times worse for an IFN-containing regimen than for IFN-free (0.10 QALY lost vs. 0.01 QALY). Only when the QoL while taking IFN was similar to that of having decompensated cirrhosis did initiating IFN-free therapy for all patients become cost-effective.

Concern that failing an initial course of PEG/RBV could compromise the efficacy of future treatment might limit enthusiasm for the ‘PEG/RBV trial’ approach. Phase 2 trials of IFN-free regimens in HCV monoinfection demonstrate a lower efficacy among treatment-experienced patients [8,9]. Such findings, however, likely demonstrate that failing PEG/RBV is a marker for having difficult to treat HCV. No data exist to suggest that first-line PEG/RBV itself decreases the efficacy of IFN-free treatment. Routine use of IFN-free regimens in budget-constrained settings will, therefore, require price negotiations for IFN-free therapy to provide acceptable value for money compared with using those funds to treat a larger number of patients with a strategy that initiates some or all patients on PEG/RBV.

There are several limitations to this analysis. First, we based efficacy estimates for protease-based therapy on phase 2 clinical trials and developed estimates for an IFN-free regimen using trials in HCV monoinfected patients. Nonetheless, the findings that the ICERs of universal triple therapy and IFN-free therapy strategies were more than $100 000/QALY at base case therapy costs were consistent across a plausible range of efficacy assumptions. Second, many HCV providers may be inclined to treat HIV/HCV coinfected cirrhotic patients with currently available therapies, but wait for the improved toxicity profile of IFN-free regimes for patients without cirrhosis [99,100]. Given the importance of therapy costs in determining the cost–effectiveness of treatment, it might also be economically attractive to defer HCV therapy for those with early-stage fibrosis until such time that a generic HCV protease inhibitor is available. Such questions of ‘treat now or defer’, though interesting, are outside the scope of this analysis, as they are critically dependent on still unknown relative efficacies of current and future therapies in early-stage and cirrhotic patients, as well as on the relative prices of multiple future drugs.

In summary, this analysis informs strategies for maximizing the population-level benefits of new HCV therapies in HIV/HCV coinfected patients. We found that in the era of ‘triple therapy,’ initiating PEG/RBV and adding TVR when patients fail to attain RVR or SVR maximizes the benefits attainable from constrained healthcare budgets. IFN-free regimens with improved efficacy may provide reasonable value, but this will depend on the cost of these regimens.

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The authors would like to thank Ms. Marion Robine for her help using the CEPAC model.

The project described was supported by grants from the National Institute on Drug Abuse (R01DA031059, R01DA027379) and the National Institute of Allergy and Infectious Diseases (R37AI042006). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.

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Conflicts of interest

There are no conflicts of interest.

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1. Ingiliz P, Rockstroh JK. HIV-HCV co-infection facing HCV protease inhibitor licensing: implications for clinicians. Liver Int 2012; 32:1194–1199.
2. Food and Drug Administration. Approval of Incivek (TVRaprevir), a direct acting antiviral drug (DAA) to treat hepatitis C (HCV). [Accessed 10 July 2013].
3. Sulkowski MS, Sherman KE, Dieterich DT, Bsharat M, Mahnke L, Rockstroh JK, et al. Combination therapy with TVRaprevir for chronic hepatitis C virus genotype 1 infection in patients with HIV: a randomized trial. Ann Intern Med 2013; 159:86–96.
4. Sulkowski M, Pol S, Mallolas J, Fainboim H, Cooper C, Slim J, et al. Boceprevir versus placebo with pegylated interferon alfa-2b and ribavirin for treatment of hepatitis C virus genotype 1 in patients with HIV: a randomised, double-blind, controlled phase 2 trial. Lancet Infect Dis 2013; 13:597–605.
5. Gilead Sciences. Gilead Submits New Drug Application to U.S. FDA for Sofosbuvir for the Treatment of Hepatitis C. [Accessed 10 July 2013].
6. Gane E, Hyland R, Ding X, Pang P, McHutchison J, Symonds W, et al.100% suppression of viral load through 4 weeks’ posttreatment for sofosbuvir + ledipasvir (GS-5885) + ribavirin for 12 weeks in treatment-naïve and -experienced hepatitis C virus GT 1 patients. In: 20th Conference on Retroviruses and Opportunistic Infection; Atlanta, GA; 3–6 March 2013.
7. Lawitz E, Cohen D, Poordad F, Kowdley K, Everson G, Freilich B, et al.12 weeks of ABT-450/ritonavir, nonnucleoside inhibitor and ribavirin achieved SVR24 in >90% of treatment-naïve hepatitis C virus GT1 patients and 47% of prior nonresponders. In: 20th Conference on Retroviruses and Opportunistic Infections; Atlanta, GA; 3–6 March 2013.
8. Jacobson IM, Gordon SC, Kowdley KV, Yoshida EM, Rodriguez-Torres M, Sulkowski MS, et al. Sofosbuvir for hepatitis C genotype 2 or 3 in patients without treatment options. N Engl J Med 2013; 368:1867–1877.
9. Lawitz E, Mangia A, Wyles D, Rodriguez-Torres M, Hassanein T, Gordon SC, et al. Sofosbuvir for previously untreated chronic hepatitis C infection. N Engl J Med 2013; 368:1878–1887.
10. Sulkowski MS. Hepatitis C virus-human immunodeficiency virus coinfection. Liver Int 2012; 32 (Suppl 1):129–134.
11. Holmberg SD, Spradling PR, Moorman AC, Denniston MM. Hepatitis C in the United States. N Engl J Med 2013; 368:1859–1861.
12. Spaulding AS, Kim AY, Harzke AJ, Sullivan JC, Linas BP, Brewer A, et al. Impact of new therapeutics for hepatitis C virus infection in incarcerated populations. Top Antivir Med 2013; 21:27–35.
13. Clark PJ, Thompson AJ, McHutchison JG. IL28B genomic-based treatment paradigms for patients with chronic hepatitis C infection: the future of personalized HCV therapies. Am J Gastroenterol 2011; 106:38–45.
14. Dayyeh BK, Gupta N, Sherman KE, de Bakker PI, Chung RT. IL28B alleles exert an additive dose effect when applied to HCV-HIV coinfected persons undergoing peginterferon and ribavirin therapy. PLoS One 2011; 6:e25753.
15. Lindh M, Lagging M, Arnholm B, Eilard A, Nilsson S, Norkrans G, et al. IL28B polymorphisms determine early viral kinetics and treatment outcome in patients receiving peginterferon/ribavirin for chronic hepatitis C genotype 1. J Viral Hepat 2011; 18:e325–e331.
16. Rallon NI, Naggie S, Benito JM, Medrano J, Restrepo C, Goldstein D, et al. Association of a single nucleotide polymorphism near the interleukin-28B gene with response to hepatitis C therapy in HIV/hepatitis C virus-coinfected patients. AIDS 2010; 24:F23–F29.
17. Linas BP, Wong AY, Schackman BR, Kim AY, Freedberg KA. Cost-effective screening for acute hepatitis C virus infection in HIV-infected men who have sex with men. Clin Infect Dis 2012; 55:279–290.
18. Liu S, Cipriano LE, Holodniy M, Owens DK, Goldhaber-Fiebert JD. New protease inhibitors for the treatment of chronic hepatitis C: a cost-effectiveness analysis. Ann Intern Med 2012; 156:279–290.
19. Linas BP, Wang B, Smurzynski M, Losina E, Bosch RJ, Schackman BR, et al. The impact of HIV/HCV co-infection on healthcare utilization and disability: results of the ACTG Longitudinal Linked Randomized Trials (ALLRT) Cohort. J Viral Hepat 2011; 18:506–512.
20. Chong CA, Gulamhussein A, Heathcote EJ, Lilly L, Sherman M, Naglie G, et al. Health-state utilities and quality of life in hepatitis C patients. Am J Gastroenterol 2003; 98:630–638.
21. Grieve R, Roberts J, Wright M, Sweeting M, DeAngelis D, Rosenberg W, et al. Cost effectiveness of interferon alpha or peginterferon alpha with ribavirin for histologically mild chronic hepatitis C. Gut 2006; 55:1332–1338.
22. Pineda JA, Aguilar-Guisado M, Rivero A, Giron-Gonzalez JA, Ruiz-Morales J, Merino D, et al. Natural history of compensated hepatitis C virus-related cirrhosis in HIV-infected patients. Clin Infect Dis 2009; 49:1274–1282.
23. Singal AG, Volk ML, Jensen D, Di Bisceglie AM, Schoenfeld PS. A sustained viral response is associated with reduced liver-related morbidity and mortality in patients with hepatitis C virus. Clin Gastroenterol Hepatol 2010; 8:280–288.288 e281.
24. Walensky RP, Sax PE, Nakamura YM, Weinstein MC, Pei PP, Freedberg KA, et al. Economic savings versus health losses: the cost-effectiveness of generic antiretroviral therapy in the United States. Ann Intern Med 2013; 158:84–92.
25. Zeuzem S, Andreone P, Pol S, Lawitz E, Diago M, Roberts S, et al. Telaprevir for retreatment of HCV infection. N Engl J Med 2011; 364:2417–2428.
26. Sulkowski M, Gardiner D, Rodriguez-Torres M, Reddy KR, Hassanein T, Jacobson IM, et al.Sustained virologic response with daclatasvir plus sofosbuvir ± ribavirin (RBV) in chronic HCV genotype (GT) 1-infected patients who previously failed TVRaprevir (TVR) or boceprevir (BOC) In: European Association for the Study of the Liver; Netherlands, Amsterdam; 24–28 April 2013.
27. United States Department of Health and Human Services Center for Medicare Services. Physician Fee Schedule. [Accessed 15 January 2013].
28. United States Department of Health and Human Services Center for Medicare Services. Clinical Diagnostic Laboratory Fee Schedule. [Accessed 1 February 2013].
29. University Health Systems Consortium. CDP Online Report. [Accessed 30 January 2013].
30. Micromedex 2.0. Drug Topics Red Book Online. [Accessed 25 June 2013].
31. United States Department of Labor Bureau of Labor Statistics. Consumer Price Index - All Urban Consumers. From: [Accessed 15 January 2013].
32. Bamezai A, Melnick G, Nawathe A. The cost of an emergency department visit and its relationship to emergency department volume. Ann Emerg Med 2005; 45:483–490.
33. Bozzette SA, Berry SH, Duan N, Frankel MR, Leibowitz AA, Lefkowitz D, et al. The care of HIV-infected adults in the United States. HIV Cost and Services Utilization Study Consortium. N Engl J Med 1998; 339:1897–1904.
34. Gebo KA, Fleishman JA, Conviser R, Hellinger J, Hellinger FJ, Josephs JS, et al. Contemporary costs of HIV healthcare in the HAART era. AIDS 2010; 24:2705–2715.
35. Levinson D. Medicaid drug price comparisons: average manufacturer price to published prices. Department of Health and Human Services. 2005. [Accessed 3 August 2013.]
36. Schackman BR, Gebo KA, Walensky RP, Losina E, Muccio T, Sax PE, et al. The lifetime cost of current human immunodeficiency virus care in the United States. Med Care 2006; 44:990–997.
37. Paltiel AD, Scharfstein JA, Seage GR 3rd, Losina E, Goldie SJ, Weinstein MC, et al. A Monte Carlo simulation of advanced HIV disease: application to prevention of CMV infection. Med Decis Making 1998; 18:S93–S105.
38. Schackman BR, Goldie SJ, Freedberg KA, Losina E, Brazier J, Weinstein MC. Comparison of health state utilities using community and patient preference weights derived from a survey of patients with HIV/AIDS. Med Decis Making 2002; 22:27–38.
39. Siebert U, Sroczynski G, Rossol S, Wasem J, Ravens-Sieberer U, Kurth BM, et al. Cost effectiveness of peginterferon alpha-2b plus ribavirin versus interferon alpha-2b plus ribavirin for initial treatment of chronic hepatitis C. Gut 2003; 52:425–432.
40. Stein K, Dalziel K, Walker A, McIntyre L, Jenkins B, Horne J, et al. Screening for hepatitis C among injecting drug users and in genitourinary medicine clinics: systematic reviews of effectiveness, modelling study and national survey of current practice. Health Technol Assess 2002; 6:1–122.
41. Fishbein DA, Lo Y, Reinus JF, Gourevitch MN, Klein RS. Factors associated with successful referral for clinical care of drug users with chronic hepatitis C who have or are at risk for HIV infection. J Acquir Immune Defic Syndr 2004; 37:1367–1375.
42. Hall CS, Charlebois ED, Hahn JA, Moss AR, Bangsberg DR. Hepatitis C virus infection in San Francisco's HIV-infected urban poor. J Gen Intern Med 2004; 19:357–365.
43. Mehta SH, Lucas GM, Mirel LB, Torbenson M, Higgins Y, Moore RD, et al. Limited effectiveness of antiviral treatment for hepatitis C in an urban HIV clinic. AIDS 2006; 20:2361–2369.
44. Strasfeld L, Lo Y, Netski D, Thomas DL, Klein RS. The association of hepatitis C prevalence, activity, and genotype with HIV infection in a cohort of New York City drug users. J Acquir Immune Defic Syndr 2003; 33:356–364.
45. Fultz SL, Justice AC, Butt AA, Rabeneck L, Weissman S, Rodriguez-Barradas M. Testing, referral, and treatment patterns for hepatitis C virus coinfection in a cohort of veterans with human immunodeficiency virus infection. Clin Infect Dis 2003; 36:1039–1046.
46. Backus LI, Boothroyd DB, Phillips BR, Mole LA. Pretreatment assessment and predictors of hepatitis C virus treatment in US veterans coinfected with HIV and hepatitis C virus. J Viral Hepat 2006; 13:799–810.
47. Pineda JA, Mira JA, Gil Ide L, Valera-Bestard B, Rivero A, Merino D, et al. Influence of concomitant antiretroviral therapy on the rate of sustained virological response to pegylated interferon plus ribavirin in hepatitis C virus/HIV-coinfected patients. J Antimicrob Chemother 2007; 60:1347–1354.
48. Zinkernagel AS, von Wyl V, Ledergerber B, Rickenbach M, Furrer H, Battegay M, et al. Eligibility for and outcome of hepatitis C treatment of HIV-coinfected individuals in clinical practice: the Swiss HIV cohort study. Antivir Ther 2006; 11:131–142.
49. Freeman AJ, Dore GJ, Law MG, Thorpe M, Von Overbeck J, Lloyd AR, et al. Estimating progression to cirrhosis in chronic hepatitis C virus infection. Hepatology 2001; 34:809–816.
50. Thein HH, Yi Q, Dore GJ, Krahn MD. Natural history of hepatitis C virus infection in HIV-infected individuals and the impact of HIV in the era of highly active antiretroviral therapy: a meta-analysis. AIDS 2008; 22:1979–1991.
51. Aparicio E, Parera M, Franco S, Perez-Alvarez N, Tural C, Clotet B, et al. IL28B SNP rs8099917 is strongly associated with pegylated interferon-alpha and ribavirin therapy treatment failure in HCV/HIV-1 coinfected patients. PLoS One 2010; 5:e13771.
52. Pineda JA, Caruz A, Di Lello FA, Camacho A, Mesa P, Neukam K, et al. Low-density lipoprotein receptor genotyping enhances the predictive value of IL28B genotype in HIV/hepatitis C virus-coinfected patients. AIDS 2011; 25:1415–1420.
53. Pineda JA, Caruz A, Rivero A, Neukam K, Salas I, Camacho A, et al. Prediction of response to pegylated interferon plus ribavirin by IL28B gene variation in patients coinfected with HIV and hepatitis C virus. Clin Infect Dis 2010; 51:788–795.
54. Torriani FJ, Rodriguez-Torres M, Rockstroh JK, Lissen E, Gonzalez-Garcia J, Lazzarin A, et al. Peginterferon Alfa-2a plus ribavirin for chronic hepatitis C virus infection in HIV-infected patients. N Engl J Med 2004; 351:438–450.
55. Reekie J, Gatell JM, Yust I, Bakowska E, Rakhmanova A, Losso M, et al. Fatal and nonfatal AIDS and non-AIDS events in HIV-1-positive individuals with high CD4 cell counts according to viral load strata. AIDS 2011; 25:2259–2268.
56. Arendt M, Munk-Jorgensen P, Sher L, Jensen SO. Mortality among individuals with cannabis, cocaine, amphetamine, MDMA, and opioid use disorders: a nationwide follow-up study of Danish substance users in treatment. Drug Alcohol Depend 2011; 114:134–139.
57. Seage GR 3rd, Holte SE, Metzger D, Koblin BA, Gross M, Celum C, et al. Are US populations appropriate for trials of human immunodeficiency virus vaccine? The HIVNET Vaccine Preparedness Study. Am J Epidemiol 2001; 153:619–627.
58. Akkarathamrongsin S, Sugiyama M, Matsuura K, Kurbanov F, Poovorawan Y, Tanaka Y, et al. High sensitivity assay using serum sample for IL28B genotyping to predict treatment response in chronic hepatitis C patients. Hepatol Res 2010; 40:956–962.
59. Kani S, Tanaka Y, Matsuura K, Watanabe T, Yatsuhashi H, Orito E, et al. Development of new IL28B genotyping method using Invader Plus assay. Microbiol Immunol 2012; 56:318–323.
60. Lin M, Rouster SD, Charlton A, Sherman KE. High-resolution melting analysis: a rapid and accurate alternative method for the detection of IL28B single-nucleotide polymorphisms. In: Conference on Retroviruses and Opportunistic Infections. Seattle; 5–8 March 2012.
61. Sangiovanni A, Prati GM, Fasani P, Ronchi G, Romeo R, Manini M, et al. The natural history of compensated cirrhosis due to hepatitis C virus: a 17-year cohort study of 214 patients. Hepatology 2006; 43:1303–1310.
62. Mellors JW, Munoz A, Giorgi JV, Margolick JB, Tassoni CJ, Gupta P, et al. Plasma viral load and CD4+ lymphocytes as prognostic markers of HIV-1 infection. Ann Intern Med 1997; 126:946–954.
63. Multicenter AIDS Cohort Study (MACS) Public Dataset: Release PO4. 1995 ed. Springfield, VA: National Technical Information Service.
64. Bozzette SA, Larsen RA, Chiu J, Leal MA, Jacobsen J, Rothman P, et al. A placebo-controlled trial of maintenance therapy with fluconazole after treatment of cryptococcal meningitis in the acquired immunodeficiency syndrome. California Collaborative Treatment Group. N Engl J Med 1991; 324:580–584.
65. Cole SR, Hernan MA, Robins JM, Anastos K, Chmiel J, Detels R, et al. Effect of highly active antiretroviral therapy on time to acquired immunodeficiency syndrome or death using marginal structural models. Am J Epidemiol 2003; 158:687–694.
66. Drew WL, Ives D, Lalezari JP, Crumpacker C, Follansbee SE, Spector SA, et al. Oral ganciclovir as maintenance treatment for cytomegalovirus retinitis in patients with AIDS. Syntex Cooperative Oral Ganciclovir Study Group. N Engl J Med 1995; 333:615–620.
67. Ioannidis JP, Cappelleri JC, Skolnik PR, Lau J, Sacks HS. A meta-analysis of the relative efficacy and toxicity of Pneumocystis carinii prophylactic regimens. Arch Intern Med 1996; 156:177–188.
68. Pedrol E, Gonzalez-Clemente JM, Gatell JM, Mallolas J, Miro JM, Graus F, et al. Central nervous system toxoplasmosis in AIDS patients: efficacy of an intermittent maintenance therapy. AIDS 1990; 4:511–517.
69. Powderly WG, Saag MS, Cloud GA, Robinson P, Meyer RD, Jacobson JM, et al. A controlled trial of fluconazole or amphotericin B to prevent relapse of cryptococcal meningitis in patients with the acquired immunodeficiency syndrome. The NIAID AIDS Clinical Trials Group and Mycoses Study Group. N Engl J Med 1992; 326:793–798.
70. Wheat J, Hafner R, Wulfsohn M, Spencer P, Squires K, Powderly W, et al. Prevention of relapse of histoplasmosis with itraconazole in patients with the acquired immunodeficiency syndrome. Ann Intern Med 1993; 118:610–616.
71. Carrat F, Bani-Sadr F, Pol S, Rosenthal E, Lunel-Fabiani F, Benzekri A, et al. Pegylated interferon alfa-2b vs standard interferon alfa-2b, plus ribavirin, for chronic hepatitis C in HIV-infected patients: a randomized controlled trial. JAMA 2004; 292:2839–2848.
72. Sherman KE, Flamm SL, Afdhal NH, Nelson DR, Sulkowski MS, Everson GT, et al. Response-guided TVRaprevir combination treatment for hepatitis C virus infection. N Engl J Med 2011; 365:1014–1024.
73. Dieterich D, Soriano V, Sherman KE, Girard P-M, Rockstroth JK, Henshaw J, et al.TVRaprevir in combination with peginterferon Alfa-2a/ribavirin in HCV/HIV co-infected patients: SVR12 interim analysis. In: Conference for Retroviruses and Opportunistic Infections; Seattle, Washington; 5–8 March 2012.
74. Mangia A, Santoro R, Minerva N, Ricci GL, Carretta V, Persico M, et al. Peginterferon alfa-2b and ribavirin for 12 vs. 24 weeks in HCV genotype 2 or 3. N Engl J Med 2005; 352:2609–2617.
75. Gallant JE, DeJesus E, Arribas JR, Pozniak AL, Gazzard B, Campo RE, et al. Tenofovir DF, emtricitabine, and efavirenz vs. zidovudine, lamivudine, and efavirenz for HIV. N Engl J Med 2006; 354:251–260.
76. Grinsztejn B, Nguyen B, Katlama C, Gatell J, Lazzarin A, Vittecog D, et al. Safety and efficacy of the HIV-1 integrase inhibitor raltegravir (MK-0518) in treatment-experienced patients with multidrug-resistant virus: a phase II randomised controlled trial. Lancet 2007; 369:1261–1269.
77. Johnson M, Grinsztejn B, Rodriguez C, Coco J, DeJesus E, Lazzarin A, et al. Atazanavir plus ritonavir or saquinavir, and lopinavir/ritonavir in patients experiencing multiple virological failures. AIDS 2005; 19:685–694.
78. Lalezari JP, Goodrich J, deJesus E, Lampiris H, Gulick R, Saag M, et al.Efficacy and safety of maraviroc plus optimized background therapy in viremic ART-experienced patients infected with CCR5-tropic HIV-1: 24-week results of a phase 2b/3 study in the US and Canada. In: Conference on Retroviruses and Opportunistic Infections; Los Angeles, CA; 25–28 February 2007.
79. Nelson M, Arasteh K, Clotet B, Cooper DA, Henry K, Katlama C, et al. Durable efficacy of enfuvirtide over 48 weeks in heavily treatment-experienced HIV-1-infected patients in the T-20 versus optimized background regimen only 1 and 2 clinical trials. J Acquir Immune Defic Syndr 2005; 40:404–412.
80. Flieishman J. Linas B; HIV loss to follow up data from the HIV Research Network. 2013.
81. Gao X, Stephens JM, Carter JA, Haider S, Rustgi VK. Impact of adverse events on costs and quality of life in protease inhibitor-based combination therapy for hepatitis C. Expert Rev Pharmacoecon Outcomes Res 2012; 12:335–343.
82. McHutchison JG, Lawitz EJ, Shiffman ML, Muir AJ, Galler GW, McCone J, et al. Peginterferon alfa-2b or alfa-2a with ribavirin for treatment of hepatitis C infection. N Engl J Med 2009; 361:580–593.
83. Schackman BR, Teixeira PA, Weitzman G, Mushlin AI, Jacobson IM. Quality-of-life tradeoffs for hepatitis C treatment: do patients and providers agree?. Med Decis Making 2008; 28:233–242.
84. Food and Drug Administration. TVRaprevir package insert. [Accessed 7 August 2013].
85. McAdam-Marx C, McGarry LJ, Hane CA, Biskupiak J, Deniz B, Brixner DI. All-cause and incremental per patient per year cost associated with chronic hepatitis C virus and associated liver complications in the United States: a managed care perspective. J Manag Care Pharm 2011; 17:531–546.
86. Daltro-Oliveira R, Morais-de-Jesus M, Pettersen KM, Parana R, Quarantini LC. Impact of sustained virologic response on quality of life in chronic HCV carriers. Ann Hepatol 2013; 12:399–407.
87. Rodger AJ, Jolley D, Thompson SC, Lanigan A, Crofts N. The impact of diagnosis of hepatitis C virus on quality of life. Hepatology 1999; 30:1299–1301.
88. Vera-Llonch M, Martin M, Aggarwal J, Donepudi M, Bayliss M, Goss T, et al. Health-related quality of life in genotype 1 treatment-naive chronic hepatitis C patients receiving TVRaprevir combination treatment in the ADVANCE study. Aliment Pharmacol Ther 2013; 38:124–133.
89. Drummond M, Sculpher M, Torrance G, O’Brien B, Stoddart G. Methods for the economic evaluation of healthcare programmes. 3rd ed.Oxford:Oxford University Press; 2005.
90. Gold M, Siegel J, Russell L, Weinstein M. Cost-effectiveness in health and medicine. New York:Oxford University Press; 1996.
91. Cantor SB. Cost-effectiveness analysis, extended dominance, and ethics: a quantitative assessment. Med Decis Making 1994; 14:259–265.
92. Ubel PA, Hirth RA, Chernew ME, Fendrick AM. What is the price of life and why doesn’t it increase at the rate of inflation?. Arch Intern Med 2003; 163:1637–1641.
93. Braithwaite RS, Meltzer DO, King JT Jr, Leslie D, Roberts MS. What does the value of modern medicine say about the $50 000 per quality-adjusted life-year decision rule?. Med Care 2008; 46:349–356.
94. Chung RT, Andersen J, Volberding P, Robbins GK, Liu T, Sherman KE, et al. Peginterferon Alfa-2a plus ribavirin versus interferon alfa-2a plus ribavirin for chronic hepatitis C in HIV-coinfected persons. N Engl J Med 2004; 351:451–459.
95. Fried MW, Hadziyannis SJ, Shiffman ML, Messinger D, Zeuzem S. Rapid virological response is the most important predictor of sustained virological response across genotypes in patients with chronic hepatitis C virus infection. J Hepatol 2011; 55:69–75.
96. Martinot-Peignoux M, Maylin S, Moucari R, Ripault MP, Boyer N, Cardoso AC, et al. Virological response at 4 weeks to predict outcome of hepatitis C treatment with pegylated interferon and ribavirin. Antivir Ther 2009; 14:501–511.
97. Poordad FF. Review article: the role of rapid virological response in determining treatment duration for chronic hepatitis C. Aliment Pharmacol Ther 2010; 31:1251–1267.
98. Gellad Z. The cost-effectiveness of a TVRaprevir-inclusive regimen as initial therapy for genotype 1 hepaticis C infection in individuals with the CC IL28B polymorphism. In: 62nd Annual Meeting of the American Association for the Study of Liver Diseases (AASLD); 4–11 November 2011; San Francisco.
99. Coffin PO, Scott JD, Golden MR, Sullivan SD. Cost-effectiveness and population outcomes of general population screening for hepatitis C. Clin Infect Dis 2012; 54:1259–1271.
100. Hagan LM, Yang Z, Ehteshami M, Schinazi RF. All-oral, interferon-free treatment for chronic hepatitis C: cost-effectiveness analyses. J Viral Hepat 2013. 1–11.

cost–effectiveness; HIV/hepatitis C virus coinfection; interferon-free; telaprevir

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