Background
Hepatitis C virus (HCV) is an important cause of liver disease in human immunodeficiency virus (HIV)–infected patients.
Objective
To assess the cost-effectiveness of alternative management strategies for chronic HCV in co-infected patients with moderate hepatitis.
Methods
A state-transition model was used to simulate a cohort of HIV-infected patients with a mean CD4 cell count of 350 cells/µL and moderate chronic hepatitis C stratified by genotype. Strategies included interferon alfa (48 weeks), pegylated interferon alfa (48 weeks), interferon alfa and ribavirin (24 and 48 weeks), pegylated interferon alfa and ribavirin (48 weeks), and no treatment. Outcomes included life expectancy, quality-adjusted life years (QALYs), and incremental cost-effectiveness ratios.
Results
Treatment for moderate chronic HCV with combination therapy using an interferon-based regimen reduced the incidence of cirrhosis and provided gains in quality-adjusted life expectancy ranging from 6.2 to 13.9 months, depending on genotype. Regardless of genotype, the cost-effectiveness of interferon alfa and ribavirin for patients with moderate hepatitis was lower than $50 000 per QALY vs the next best strategy. With genotype 1, pegylated interferon alfa (vs interferon alfa) and ribavirin therapy provided an additional 1.6 quality-adjusted life-months for $40 000 per QALY. Because treatment is more effective with non-1 genotypes, pegylated interferon (vs interferon alfa) and ribavirin provided only 3 additional quality-adjusted life-months for $105 300 per QALY. For patients who were intolerant of ribavirin, monotherapy with pegylated interferon was always the most cost-effective option.
Conclusions
Combination therapy for moderate hepatitis in coinfected patients will increase quality-adjusted life expectancy and have a cost-effectiveness ratio comparable to that of other well-accepted clinical interventions.
APPROXIMATELY ONE third of all human immunodeficiency virus (HIV)–infected persons in the United States are coinfected with hepatitis C virus (HCV).1-3 Although the prognosis for HIV infection has improved dramatically with the availability of highly active antiretroviral therapy (HAART),4,5 coinfected patients are now vulnerable to the complications associated with long-term HCV infection (eg, cirrhosis).6-9 Numerous studies10-20 report an increase in hospital admissions and deaths due to liver disease in HIV-infected patients. Compared with HIV-uninfected patients, coinfected patients have higher levels of HCV RNA21-25 and a greater risk of progression to severe liver disease.2,6,7,19,24-39 Hepatitis C virus may also have a negative impact on HIV disease progression, although this issue remains controversial.2,19,38,40-45
Clinical trials46-52 have documented the enhanced antiviral efficacy of combination therapy with ribavirin and interferon alfa, with sustained treatment responses ranging from 33% to 49%. Moreover, multiple studies53-63 focusing on HIV-uninfected patients have shown that the cost-effectiveness of treatment for chronic HCV is comparable to that of other well-accepted standard preventive interventions. Recently, treatment with pegylated interferon alfa (with and without ribavirin), a long-acting variant of interferon alfa that requires less frequent dosing, has been shown to have higher efficacy than use of interferon alfa alone.64-70 The cost-effectiveness of pegylated interferon alfa therapy has not yet been explored in either HIV-infected or HIV-uninfected patients.
The longer expected survival of HIV-infected patients receiving HAART, coupled with the potentially accelerated progression of HCV-related liver disease, has resulted in a set of complex clinical and policy questions. Treatment recommendations for HIV-uninfected patients may not be directly applicable to coinfected patients.71-75 Although information from ongoing clinical studies in coinfected patients is anticipated in the next several years, the ideal source of data—long-term placebo-controlled trials of all potential treatment strategies—is not likely to be feasible. For many coinfected patients, treatment decisions must be made now, in the setting of considerable uncertainty and despite the absence of perfect information. To inform these decisions, we incorporated the best available data to assess the health and economic consequences of a variety of strategies to manage HCV-related liver disease in HIV-infected patients.
A computer-based mathematical model was used to compare the following strategies for the management of moderate chronic HCV in coinfected patients with CD4 cell counts greater than 350 cells/µL: (1) no HCV treatment, (2) monotherapy with interferon alfa (48 weeks), (3) monotherapy with pegylated interferon alfa (48 weeks), (4) combination therapy with interferon alfa and ribavirin (24 and 48 weeks), and (5) combination therapy with pegylated interferon alfa and ribavirin (48 weeks). Analyses were stratified by HCV genotype because distributions of genotypes vary in different patient subgroups and affect response to therapy.64,65,76 We adopted a societal perspective and followed the recommendations of the Panel on Cost-effectiveness in Health and Medicine.77 Model outcomes included quality-adjusted life expectancy (QALE) and total lifetime costs. Comparative performance of alternative strategies was measured by the incremental cost-effectiveness ratio, defined as the additional cost of a specific treatment strategy divided by its additional clinical benefit compared with the next least-expensive strategy. We conducted univariate and multivariate sensitivity analyses to assess variable uncertainty, and we explored the effect of alternative assumptions compared with those made in the base case.
A deterministic state-transition Markov model (DATA 3.5; TreeAge Software Inc, Williamstown, Mass) was used to simulate the natural history of HCV-induced liver disease in coinfected patients (Figure 1). Health states were defined to reflect 5 broad categories of HCV-related liver disease (mild chronic HCV, moderate chronic HCV, compensated cirrhosis, decompensated cirrhosis, and hepatocellular carcinoma [HCC]), stage of HIV disease (CD4 cell count >500, 200-500, and <200 cells/µL), and treatment status with HAART. Decompensated cirrhosis was defined as the presence of complications of portal hypertension, such as ascites, variceal bleeding, or hepatic encephalopathy.
In the base case, a cohort of coinfected individuals entered the model with a mean CD4 cell count of 350 cells/µL and histologically moderate chronic hepatitis. Transition probabilities from the literature were used to move individuals through different health states over time. The time horizon of the analysis was divided into equal increments during which patients could progress to later stages of HCV or HIV. Each month, patients could progress from mild to moderate hepatitis or from moderate hepatitis to cirrhosis. Patients with cirrhosis could develop complications (ie, decompensated cirrhosis) or primary HCC. In the absence of HAART, patients could progress from higher to lower CD4 cell strata. We conservatively assumed that HIV progression was independent of HCV but explored the implications of a more rapid progression to acquired immunodeficiency syndrome. Each month, patients faced competing mortality risks from advanced liver disease, acquired immunodeficiency syndrome, and other causes.
We made the following assumptions: (1) HCV treatment was discontinued in patients not responding to monotherapy after 3 months or combination therapy after 6 months71,72,74; (2) HCV treatment resulted in 1 of 3 potential outcomes—no treatment response, a partial but nonsustained response, or a sustained response; (3) patients with no treatment response received no clinical benefit and were subject to their annual pretreatment risk of HCV-related liver disease progression; (4) patients with a partial but nonsustained response did not progress in their HCV-related liver disease during treatment but were subject to pretreatment risks of liver disease once treatment was stopped; (5) patients with a sustained response (ie, undetectable HCV RNA for >6 months after treatment) did not experience a future risk of HCV-related liver disease, although the implications of relapse were evaluated in sensitivity analysis; (6) response to treatment was conditional on genotype; (7) the rate of liver disease progression in the absence of treatment was independent of genotype; (8) minor adverse effects of treatment resulted in additional costs and a temporary decrease in quality of life, whereas major toxicity due to treatment resulted in treatment discontinuation; (9) patients were eligible to receive 4 sequential regimens of HAART for HIV78,79; and (10) coinfected patients with decompensated cirrhosis or HCC were not eligible for liver transplantation. Alternative assumptions were evaluated in sensitivity analysis.
The variable estimates and plausible ranges used in the base case analysis are shown in Table 1.70-109110-138 A summary of selected clinical studies used to establish the plausible ranges for variables related to the relationship between HIV and HCV, and the efficacy of treatment for HCV, is available from the authors.139-148 In HIV-uninfected patients, progression from chronic HCV to cirrhosis and HCC may take up to several decades.8,9 The risk of cirrhosis implied by cohort studies149-153 of chronically infected patients ranges from 8% to 50% after 1 to 2 decades, although these studies are subject to referral bias because most were performed at tertiary referral centers. A much slower rate of progression has been implied from prospective cohort studies80,88,154-159 of acutely infected patients after transfusion or during defined periods of exposure.
To estimate the probabilities of progression from compensated to decompensated cirrhosis as well as the risk of HCC and death, a series of calibration exercises was conducted using one of the largest published studies of cirrhotic patients with chronic HCV.91 First, we used the model to simulate the course of chronic HCV in an HIV-uninfected cohort and projected several clinical outcomes, including decompensated cirrhosis, HCC, and death. Second, the probabilities of disease progression were adjusted until the model outcome projections closely matched the observed data.91 Finally, these disease progression probabilities were adjusted to reflect the increased risk of advanced liver disease reported in coinfected patients.2,21-25,27,29-39,160-164 In the base case, we conservatively assumed a relative risk (RR) of progression to cirrhosis of 2 compared with HIV-uninfected patients, but varied it from 1 (ie, no increased risk compared with HIV-uninfected patients) to 5 in sensitivity analysis.
The natural history of HIV disease was modeled by stratifying health states by CD4 cell counts, as was done in previous studies.138,165 To incorporate the impact of HAART, we first extrapolated average probabilities of CD4 cell decline and HIV-related mortality using published data.166-168 Because health states were not stratified by HIV RNA level, we calibrated our simplified model to results obtained with a previously described computer-based simulation model of HIV disease that includes both HIV RNA and CD4 cell count as predictors of disease progression.101-103 Assuming a hypothetical cohort of 1 million HIV-infected adults with a mean CD4 cell count of 350 cells/µL, the probabilities of CD4 decline and HIV-related mortality were adjusted such that projected life expectancy, QALE, and costs for both models converged.
Details of this more comprehensive HIV policy model have been published elsewhere.101-103 Briefly, it is a state-transition model programmed in C and compiled with Visual C++ 6.0 (Microsoft Corp, Redmond, Wash) in which the risks of opportunistic infections and death are stratified by CD4 cell count and the rate of CD4 cell decline is determined by level of HIV RNA. Methods used to derive the transition probabilities for antiretroviral treatment efficacy in this model are described elsewhere101-103 and are based on data from several clinical trials.166-171 Data have also been incorporated regarding the initiation, discontinuation, efficacy, and toxic effects of prophylaxis against major opportunistic infections.101-103
We assumed that the efficacy of combination regimens for chronic HCV in coinfected patients was the same as in HIV-uninfected patients, although we explored lower rates of response in sensitivity analyses.140-148,163 We used data from several studies172-184 to estimate a plausible range for the risk of minor and major toxic effects from HCV treatment or HAART.
Health-related quality of life
The consequences of mortality and morbidity were incorporated into a single outcome measure by adjusting life expectancy for quality of life on a scale from 0 (death) to 1 (perfect health). Data were not available for the specific health states in our model, which reflect coinfection with HCV and HIV. Therefore, we assumed a multiplicative relationship using the quality weights derived for each disease separately.185,186 The quality weights for the HCV-specific health states were from published studies using the visual analog scale. We calculated utilities from these values using a rating scale transformation derived by Torrance.187 The quality weights for the HIV-specific health states were derived from recent works107-110 based on data from the HIV Cost and Services Utilization Study.
An increasing number of studies106,111-124,188,189 document the impact of chronic HCV on health-related quality of life. We conservatively assumed that the quality of life benefit associated with treating moderate hepatitis was captured by averting progression to cirrhosis. We explored the effect of temporary decrements in quality of life associated with treatment (due to adverse effects and medication toxic effects) for chronic HCV.172,173
We used previously published estimates for the direct medical costs associated with chronic HCV that were based on a cost accounting approach and combined unit cost estimates for office visits, hospitalizations, laboratory tests, and medications, with resource utilization frequency estimated by an expert panel.55 Drug costs were based on average wholesale prices.128,132 Because of a wide discrepancy in costs based on compounded vs separately marketed drugs, a wide plausible range was used in sensitivity analyses.63,125,130,131 To account for inflation, all costs were converted to constant dollars using the Medical Care Component of the Consumer Price Index.129
Costs of monthly HIV care were based on previously published data and reflected routine HIV care, antiretroviral drug costs, HIV RNA testing every 3 months, and resistance testing after virologic failure after the first HAART regimen.101-103 The costs of genotypic resistance tests, CD4 tests, and HIV RNA and HCV RNA assays were obtained from the public use Clinical Diagnostic Laboratory Fee Schedule.134 Estimates were similar to other sources of costs attributable to HIV and acquired immunodeficiency syndrome.135
Predictive validity of the natural history model
We compared the model's predictions of cirrhosis and mortality with data from published studies that were not used for variable estimation. For an HIV-infected cohort with mild chronic HCV, our model predicted a cumulative risk of cirrhosis after 10 years of 16.9% compared with 14.9% reported by Soto et al.37 The model predicted that 90% of deaths were attributable to HIV disease and that 5% were attributable to HCV compared with the 89% and 5%, respectively, observed by Puoti et al.17
For a cohort of 35-year-old coinfected patients (mean CD4 cell count of 350 cells/µL) with moderate HCV, the average discounted QALE was 83.8 months, and lifetime costs were $139 000 (Table 2). In patients with genotype 1, treatment for HCV provided incremental gains ranging from 6.2 to 7.8 quality-adjusted life-months compared with no therapy. Combination therapy with interferon alfa and ribavirin for 48 weeks dominated combination therapy for 24 weeks and interferon alfa alone because it was more effective and had a lower (more attractive) cost-effectiveness ratio. Compared with no therapy, its incremental cost-effectiveness ratio was $11 600 per quality-adjusted life-year (QALY). In comparison, combination therapy with pegylated interferon alfa and ribavirin for 48 weeks provided an additional 1.6 quality-adjusted months of life for a cost of $40 000 per QALY.
Treatment provided even greater QALE gains in individuals with non-1 genotypes. Combination therapy with interferon alfa and ribavirin for 24 weeks provided 12.3 quality-adjusted life-months and had an incremental cost-effectiveness ratio of $2900 per QALY compared with no therapy. Combination therapy for 48 weeks provided 1.0 additional month of life expectancy and cost $38 800 per QALY compared with a 24-week course. In comparison, pegylated interferon alfa and ribavirin for 48 weeks provided an additional 3 weeks and cost $105 300 per QALY gained.
For an otherwise identical cohort of coinfected patients with mild chronic HCV, QALE gains were lower, reflecting their overall lower risk of progression to cirrhosis. In those with genotype 1, combination therapy with interferon alfa and ribavirin for 48 weeks increased QALE by 2.2 months and cost $35 900 per QALY compared with no therapy. In comparison, pegylated interferon alfa and ribavirin therapy for 48 weeks increased QALE by 3 weeks and cost $113 100 per QALY. In those with genotypes other than 1, interferon alfa and ribavirin administration for 24 weeks increased the QALE by 4.5 months and cost $11 900 per QALY compared with no treatment. The additional clinical benefits achieved with 48 weeks of combination therapy with either regular interferon alfa or pegylated interferon alfa ranged from 2 to 3 weeks and cost $112 100 and $300 800 per QALY, respectively.
Results were most sensitive to the RR of progression to cirrhosis compared with HIV-negative patients, the ability to tolerate HAART, and the discount rate (Figure 2). Results were moderately sensitive to the long-term effectiveness and cost of treatment for HCV. General results were minimally sensitive to the direct medical costs associated with HIV disease, a potential treatment effect in nonresponders, and minor toxic effects. The impact of major toxic effects depended on assumptions made about the necessity for long-term treatment interruptions with HAART.
Figure 3 shows the relationship between the RR of progression to cirrhosis in coinfected patients with mild and moderate chronic HCV compared with HIV-uninfected patients and the incremental cost-effectiveness ratios for combination therapy compared with the next best treatment strategy. General results for patients with genotype 1 (Figure 3 A) and non-1 genotypes (Figure 3 B) are similar, although the optimal strategies for treatment differ. For patients with genotype 1, even with an RR of 1 the gains in QALE ranged from 4.04 to 5.12 months. For this conservative scenario, the incremental cost-effectiveness ratio for combination therapy with interferon alfa and ribavirin was $18 800 per QALY compared with no therapy. In comparison, treatment with pegylated interferon alfa and ribavirin for 48 weeks was $62 000 per QALY. As the RR was increased from 1 (ie, risk is no different than in HIV-uninfected patients) to 5, the incremental benefits associated with treatment increased and the cost-effectiveness ratios became more attractive. The impact on the cost-effectiveness ratios associated with treatment was most pronounced between an RR of 1 and 2, with less effect observed at RRs higher than 3. Changes in the RR had a greater effect on patients with mild HCV than with moderate HCV because the former have a lower baseline probability of disease progression.
We explored the potential implications of major toxicity resulting from the use of interferon alfa and ribavirin if such toxic effects resulted in a 50% reduction in the effectiveness of HAART (eg, secondary to a lower rate of adherence or necessity for discontinuation of HAART). Under these exploratory and hypothetical conditions, if 20% of patients experienced major toxicity resulting from 48 weeks of combination therapy with pegylated interferon alfa and ribavirin, the incremental cost-effectiveness ratio increased from $40 600 to $69 000 per QALY with genotype 1 compared with the next best strategy. In contrast, minor adverse affects from treatment had little effect on the results.
In coinfected patients with mild chronic hepatitis, results were sensitive to assumptions about the impact of treatment on quality of life. The life expectancy benefits from treating mild HCV ranged from 1 to 2 weeks, whereas the QALE benefits ranged from 2 weeks to nearly 2 months (Table 2). These results demonstrate that a substantial proportion of the clinical benefit associated with treating mild chronic HCV results from averting progression to moderate HCV, which is associated with a poorer quality of life.
For patients with moderate HCV and genotype 1, the cost-effectiveness of pegylated interferon alfa and ribavirin therapy was sensitive to assumptions about the potential quality of life benefits associated with a single weekly injection compared with the 3 weekly injections needed for regular interferon alfa. We conducted a threshold analysis to identify the quality of life decrement associated with 3 weekly subcutaneous injections that would make pegylated interferon alfa plus ribavirin the preferred strategy. We found that if the quality of life during 48 weeks of treatment was reduced by more than 10%, combination therapy with pegylated interferon alfa and ribavirin dominated conventional interferon alfa–based strategies.
We conducted an exploratory analysis for patients with CD4 cell counts below 200 cells/µL. For coinfected patients in later stages of HIV with CD4 cell counts below 200 cells/µL and with moderate HCV, the general results were similar, although all cost-effectiveness ratios were higher, reflecting the increased competing morbidity and mortality associated with HIV disease (Table 2). In sensitivity analysis, when the efficacy of HAART was increased such that life expectancy approached that of the average patient in the base case cohort, the cost-effectiveness ratios associated with HCV treatment consistently declined below $50 000 per QALY.
We also evaluated the cost-effectiveness of interferon alfa–based monotherapy in coinfected patients intolerant of ribavirin. For these patients, monotherapy with pegylated interferon alfa was the most effective option. Compared with regular interferon alfa therapy, the cost-effectiveness ratio associated with use of pegylated interferon alfa was $29 400 per QALY in patients with genotype 1 and $20 300 per QALY in patients with non-1 genotypes.
We found that for HIV-infected patients with moderate chronic HCV and a mean CD4 cell count of 350 cells/µL, treatment with combination therapy using an interferon alfa–based regimen reduced the incidence of cirrhosis and provided substantial gains in QALE. Regardless of genotype, the cost-effectiveness of interferon alfa and ribavirin therapy for patients with moderate HCV was less than $50 000 per QALY.
The incremental benefits and cost-effectiveness of pegylated interferon alfa and ribavirin therapy for 48 weeks (compared with use of regular interferon alfa and ribavirin for 24 and 48 weeks) differed between individuals with genotype 1 and non-1 genotypes. Combination therapy (pegylated interferon alfa and ribavirin) in patients with moderate HCV and genotype 1 cost less than $50 000 per QALY. In contrast, because treatment is relatively more effective in patients with non-1 genotypes, the incremental gain in QALE associated with the more costly pegylated interferon alfa, compared with regular interferon alfa and ribavirin, was relatively small. Accordingly, although the cost-effectiveness ratio of interferon alfa and ribavirin therapy for non-1 genotypes was less than $50 000 per QALY compared with no treatment, combination therapy with pegylated interferon alfa exceeded $100 000 per QALY. For all patients, regardless of genotype, if ribavirin was not tolerated, monotherapy with pegylated interferon alfa was the best option.
There is considerable uncertainty in the natural history of chronic HCV, although recent data indicate that the RR of liver disease progression seems to be increased in coinfected patients compared with HIV-uninfected patients.2,6,17,19,24-37 We assumed an RR of 2 for progression of liver disease compared with HIV-uninfected patients, but all analyses were repeated using the more conservative assumption of an RR of 1. When we assumed that the risk of liver disease was no different than in HIV-uninfected patients, the life expectancy gains and cost-effectiveness ratios associated with treatment for moderate HCV were comparable or superior to those provided by prophylaxis for opportunistic infections. In contrast, the cost-effectiveness of treatment for mild HCV was more sensitive to assumptions about the RR of HCV progression in HIV-infected vs HIV-uninfected patients. Unless this RR was 2 or greater, the incremental cost-effectiveness ratio for combination therapy exceeded $50 000 per QALY. These results highlight the importance of obtaining better data to inform the attributable excess risk associated with HIV coinfection. The results of this analysis indicate that the information with the greatest potential value will be that providing detail on whether the RR is closer to 1 or 2 in coinfected compared with HIV-uninfected patients.
Detailed data on the interactions between the tolerance and effectiveness of HAART and treatment for HCV are not yet available, to our knowledge. Therefore, the goal of our exploratory analyses examining the implications of these interactions was to provide qualitative insight into the importance of certain variables but not to answer questions for which data are not yet available. We found that changes in HCV treatment efficacy and minor toxic effects, when varied over a wide plausible range, had a minimal effect on our major results. In contrast, there was a greater effect of major toxic effects when they resulted in a lower efficacy of HAART. Without the clinical benefits associated with HAART, patients experienced HIV disease progression before the development HCV-related end-stage liver disease; thus, they received minimal life-extending benefit from HCV treatment despite accruing its treatment costs. On the other hand, it is equally plausible that treatment for HCV could improve the probability of tolerance to HAART by reducing the risk of hepatotoxicity. If this turns out to be true, HCV treatment will provide even greater clinical benefits and be even more cost-effective. These results indicate that better information on whether HCV treatment limits or enhances tolerability to HAART should be a high priority.
This study has several additional limitations. The natural history of HCV is uncertain in HIV-uninfected patients and in HIV-infected patients undergoing HAART. The efficacy and toxic effects of HCV therapy in HIV-infected patients have only been assessed in relatively small clinical studies. There are no published data, to our knowledge, on the quality of life associated with coinfection, stratified by stage of HIV disease, that are suitable for weighting the specific health states in our model. We assumed a multiplicative relationship between the quality weights for HIV and HCV, but empiric data to inform the validity of this assumption are lacking. The quality of life benefits associated with use of pegylated interferon alfa, recently approved by the Food and Drug Association for treatment of chronic HCV, remain unclear. Our results indicate that, in theory, if HCV could be treated before an individual's need for HAART (thereby eliminating any potential negative consequences of HCV treatment on tolerance of HAART or preventing hepatotoxicity of HAART), such a strategy would likely be effective and cost-effective. It is possible that temporary interruptions in HAART due to HCV treatment toxic effects will be less detrimental than we assumed; in this case, the negative impact of toxic effects was overestimated. Our results do not address the question of whether treatment for HCV should be administered much earlier in the disease progression (eg, CD4 cell counts >500 cells/µL). Data in these patients are lacking but will be important to incorporate when available. A key attribute of a model such as this one is that as better data become available, the impact of new information can be rapidly evaluated. In the meantime, however, clinical decisions for individuals and broader public policy decisions must proceed before all uncertainties are resolved.
Evaluating the effectiveness of HCV treatment in coinfected patients requires specification of the natural history of both diseases (HIV and HCV), consideration of the heterogeneity of risk, treatment efficacy and toxic effects, and accessibility, feasibility, and affordability of medication and health care. Data are not available for all of this information, and our analysis therefore required multiple assumptions. However, even in the future, a single study will not be able to simultaneously consider all of these components and assess all possible strategies for all relevant populations. This analysis was conducted to provide qualitative and quantitative insight into the relative importance of different components of the treatment process and to investigate how results would change when values of key variables were changed. By identifying the most influential variables, these results may be used to help prioritize and guide data collection efforts. Our results suggest that the most critical variables for future research include the RR of progression in chronic HCV, the health-related quality of life in coinfected patients with mild HCV, and the ability to tolerate treatment for HIV with HAART.
Based on conservative assumptions about the natural history of HCV and treatment efficacy, coinfected patients with a CD4 cell count of at least 350 cells/µL and moderate chronic HCV should be treated with combination therapy. In patients able to tolerate combination therapy, the choice of pegylated vs standard interferon alfa (in combination with ribavirin) depends on the genotype (and likelihood of sustained treatment response to traditional interferon alfa and ribavirin) and assumptions about the quality of life decrement associated with 3 subcutaneous injections per week. Patients who are intolerant of ribavirin therapy should be treated with pegylated interferon alfa regardless of genotype.
Accepted for publication April 24, 2002.
This study was presented in part at the meeting of the Society of Medical Decision Making, Cincinnati, Ohio, September 25, 2000.
Corresponding author and reprints: Sue J. Goldie, MD, MPH, Harvard Program on the Economic Evaluation of Medical Technology, 718 Huntington Ave, Second Floor, Boston, MA 02115-5924 (e-mail: sgoldie@hsph.harvard.edu).
1.Bonacini
MPuoti
M Hepatitis C in patients with human immunodeficiency virus infection: diagnosis, natural history, meta-analysis of sexual and vertical transmission, and therapeutic issues.
Arch Intern Med 2000;1603365- 3373
Google ScholarCrossref 2.Dieterich
DT Hepatitis C virus and human immunodeficiency virus: clinical issues in coinfection.
Am J Med. 1999;107
((suppl))
79S- 84S
Google ScholarCrossref 3.Soriano
VRodriguez-Rosado
RGarcia-Samaniego
J Management of chronic hepatitis C in HIV-infected patients.
AIDS. 1999;13539- 546
Google ScholarCrossref 4.Palella
FJ
JrDelaney
KMMoorman
AC
et al. Declining morbidity and mortality among patients with advanced human immunodeficiency virus infection.
N Engl J Med. 1998;338853- 860
Google ScholarCrossref 5.Kaplan
JEHanson
DDworkin
MS
et al. Epidemiology of human immunodeficiency virus–associated opportunistic infections in the United States in the era of highly active antiretroviral therapy.
Clin Infect Dis. 2000;30
((suppl 1))
S5- S14
Google ScholarCrossref 7.Soriano
VGarcia-Samaniego
JRodriguez-Rosado
RGonzalez
JPedreira
J Hepatitis C and HIV infection: biological, clinical, and therapeutic implications.
J Hepatol. 1999;31119- 123
Google ScholarCrossref 9.Alter
HJSeeff
LB Recovery, persistence, and sequelae in hepatitis C virus infection: a perspective on long-term outcome.
Semin Liver Dis. 2000;2017- 35
Google ScholarCrossref 10.Bica
IMcGovern
BDhar
R
et al. Increasing mortality due to end-stage liver disease in patients with human immunodeficiency virus infection.
Clin Infect Dis. 2001;32492- 497
Google ScholarCrossref 11.Valdez
HChowdhry
TKAsaad
R
et al. Changing spectrum of mortality due to human immunodeficiency virus: analysis of 260 deaths during 1995-1999.
Clin Infect Dis. 2001;321487- 1493
Google ScholarCrossref 12.Soriano
VMartin-Carbonero
LGarcia-Samaniego
JPuoti
M Mortality due to chronic viral liver disease among patients infected with human immunodeficiency virus.
Clin Infect Dis. 2001;331793- 1795
Google ScholarCrossref 13.Bonnet
FMorlat
PChene
G
et al. Causes of death among HIV-infected patients in the era of highly active antiretroviral therapy: Aquitane Cohort France, 1998-1999. Paper presented at: 8th Conference on Retroviruses and Opportunistic Infections February 4-8, 2001 Chicago, IllAvailable at:
http://www.retroconference.org/2001/abstracts/abstracts/abstracts/299.htm. Accessed April 23, 2001. Abstract 299
14.Di Perri
GRaiteri
RBonora
S
et al. Liver failure from HCV as the current leading cause of death in HIV-infected patients in Northern Italy. Paper presented at: 8th Conference on Retroviruses and Opportunistic Infections February 4-8, 2001 Chicago, IllAvailable at:
http://www.retroconference.org/2001/abstracts/abstracts/abstracts/573.htm. Accessed April 23, 2001. Abstract 573
15.Ahmad
SPulvirenti
JShastri
PIrfan
MAriga
D Death in HIV-infected inpatients in the HAART era: an evaluation of mortality in an inner-city hospital. Paper presented at: 8th Conference on Retroviruses and Opportunistic Infections February 4-8, 2001 Chicago, IllAvailable at:
http://www.retroconference.org/2001/abstracts/abstracts/abstracts/300.htm. Accessed April 23, 2001. Abstract 300
16.Justice
AChang
CFusco
J
et al. Extrapolating long-term HIV/AIDS survival in the post-HAART era. Program and abstracts of the 39th International Conference on Antimicrobial Agents and Chemotherapy September 26-29, 1999 San Francisco, CalifAbstract 1158
17.Puoti
MSpinetti
AGhezzi
A
et al. Mortality for liver disease in patients with HIV infection: a cohort study.
J Acquir Immune Defic Syndr. 2000;24211- 217
Google ScholarCrossref 18.Martin-Carbonero
LSoriano
VValencia
MLopez
MGonzalez-Lahoz
J Impact of chronic viral hepatitis on hospital admission and mortality in HIV-infected patients. Paper presented at: 8th Conference on Retroviruses and Opportunistic Infections February 4-8, 2001 Chicago, IllAvailable at:
http://www.retroconference.org/2001/abstracts/abstracts/abstracts/297.htm. Accessed April 23, 2001). Abstract 297
20.Kim
WRGross
JB
JrPoterucha
JJLocke
GRDickson
ER Outcome of hospital care of liver disease associated with hepatitis C in the United States.
Hepatology. 2001;33201- 206
Google ScholarCrossref 21.Telfer
PSabin
CDevereux
HScott
FDusheiko
GLee
C The progression of HCV-associated liver disease in a cohort of haemophilic patients.
Br J Haematol. 1994;87555- 561
Google ScholarCrossref 22.Cribier
BRey
DSchmitt
C
et al. High hepatitis C viraemia and impaired antibody response in patients coinfected with HIV.
AIDS. 1995;91131- 1136
Google ScholarCrossref 23.Beld
MPenning
MLukashov
V
et al. Evidence that both HIV and HIV-induced immunodeficiency enhance HCV replication among HCV seroconverters.
Virology. 1998;244504- 512
Google ScholarCrossref 24.Thomas
DLShih
JWAlter
HJ
et al. Effect of human immunodeficiency virus on hepatitis C virus infection among injecting drug users.
J Infect Dis. 1996;174690- 695
Google ScholarCrossref 25.Eyster
MEDiamondstone
LSLien
JMEhmann
WCQuan
SGoedert
JJ Natural history of hepatitis C virus infection in multitransfused hemophiliacs: effect of coinfection with human immunodeficiency virus: the Multicenter Hemophilia Cohort Study.
J Acquir Immune Defic Syndr. 1993;6602- 610
Google Scholar 26.Graham
CBaden
LRYu
E
et al. Influence of human immunodeficiency virus infection on the course of hepatitis C virus infection: a meta-analysis.
Clin Infect Dis. 2001;33562- 569
Google ScholarCrossref 27.Allory
YCharlotte
FBenhamou
YOpolon
PLe Charpentier
YPoynard
T Impact of human immunodeficiency virus infection on the histological features of chronic hepatitis C: a case-control study.
Hum Pathol. 2000;3169- 74
Google ScholarCrossref 28.Pol
SLamorthe
BThi
NT
et al. Retrospective analysis of the impact of HIV infection and alcohol use on chronic hepatitis C in a large cohort of drug users.
J Hepatol. 1998;28945- 950
Google ScholarCrossref 29.Ragni
MVBelle
SH Impact of human immunodeficiency virus infection on progression to end-stage liver disease in individuals with hemophilia and hepatitis C virus infection.
J Infect Dis. 2001;1831112- 1115
Google ScholarCrossref 30.Benhamou
YBochet
MDi Martino
V
et al. for the Multivirc Group, Liver fibrosis progression in human immunodeficiency virus and hepatitis C virus coinfected patients.
Hepatology. 1999;301054- 1058
Google ScholarCrossref 31.Benhamou
YBochet
MDi Martino
V
et al. Anti-protease inhibitor therapy decreases the liver fibrosis progression rate in HIV-HCV coinfected patients [abstract].
Hepatology. 1999;30362A
Google Scholar 32.Darby
SWewart
DGiangrande
P
et al. Mortality from liver cancer and liver disease in haemophilic men and boys in UK given blood products contaminated with hepatitis C.
Lancet. 1997;3501425- 1431
Google ScholarCrossref 33.Garcia-Samaniego
JSoriano
VCastilla
J
et al. Influence of hepatitis C virus genotypes and HIV infection on histological severity of chronic hepatitis C.
Am J Gastroenterol. 1997;921130- 1134
Google Scholar 34.Lesens
ODeschenes
MSteben
MBelanger
GTsoukas
CM Hepatitis C virus is related to progressive liver disease in human immunodeficiency virus–positive hemophiliacs and should be treated as an opportunistic infection.
J Infect Dis. 1999;1791254- 1258
Google ScholarCrossref 35.Puoti
MPatroni
AZanini
S
et al. Hepatitis virus coinfections, antiretrovirals hepatotoxicity, and risk of death in HIV-infected persons: prospective cohort study. Paper presented at: 8th Conference on Retroviruses and Opportunistic Infections February 4-8, 2001 Chicago, IllAvailable at:
http://www.retroconference.org/2001/abstracts/abstracts/abstracts/576.htm. Accessed April 23, 2001. Abstract 576
36.Sanchez-Quijano
AAndreu
JGavilan
F
et al. Influence of human immunodeficiency virus type 1 infection on the natural course of chronic parenterally acquired hepatitis C.
Eur J Clin Microbiol Infect Dis. 1995;14949- 953
Google ScholarCrossref 37.Soto
BSanchez-Quijano
ARodrigo
L
et al. Human immunodeficiency virus infection modifies the natural history of chronic parenterally-acquired hepatitis C with an unusually rapid progression to cirrhosis.
J Hepatol. 1997;261- 5
Google ScholarCrossref 38.Wright
TLHollander
HPu
X
et al. Hepatitis C in HIV-infected patients with and without AIDS: prevalence and relationship to patient survival.
Hepatology. 1994;201152- 1155
Google ScholarCrossref 39.Zylberberg
HPol
S Reciprocal interactions between human immunodeficiency virus and hepatitis C virus infections.
Clin Infect Dis. 1996;231117- 1125
Google ScholarCrossref 40.Daar
ELynn
HGomperts
E
et al. for the Hemophilia Growth and Development Study, Hepatitis C virus load is associated with human immunodeficiency virus type 1 disease progression in hemophiliacs.
J Infect Dis. 2001;183589- 595
Google ScholarCrossref 41.Sulkowski
MSMast
EESeeff
LBThomas
DL Hepatitis C virus infection as an opportunistic disease in persons infected with human immunodeficiency virus.
Clin Infect Dis. 2000;30
((suppl 1))
S77- S84
Google ScholarCrossref 42.Greub
GLedergerber
BBattegay
M
et al. Clinical progression, survival, and immune recovery during antiretroviral therapy in patients with HIV-1 and hepatitis C virus coinfection: the Swiss HIV Cohort Study.
Lancet. 2000;3561800- 1805
Google ScholarCrossref 44.Piroth
LGrappin
MCuzin
L
et al. Hepatitis C virus co-infection is a negative prognostic factor for clinical evolution in human immunodeficiency virus–positive patients.
J Viral Hepat. 2000;7302- 308
Google ScholarCrossref 46.Kjaergard
LLKrogsgaard
KGluud
C Interferon alfa with or without ribavirin for chronic hepatitis C: systematic review of randomised trials.
BMJ. 2001;3231151- 1155
Google ScholarCrossref 47.Poynard
TMarcellin
PLee
SS
et al. for the International Hepatitis Interventional Therapy Group (IHIT), Randomised trial of interferon alpha2b plus ribavirin for 48 weeks or for 24 weeks versus interferon alpha2b plus placebo for 48 weeks for treatment of chronic infection with hepatitis C virus.
Lancet. 1998;3521426- 1432
Google ScholarCrossref 48.Reichard
ONorkrans
GFryden
ABraconier
J-HSönnerborg
AWeiland
O Randomized, double-blind, placebo-controlled trial of interferon alpha-2b with and without ribavirin for chronic hepatitis C.
Lancet. 1998;35183- 87
Google ScholarCrossref 49.McHutchison
JGGordon
SCSchiff
ER
et al. Interferon alfa-2b alone or in combination with ribavirin as initial treatment for chronic hepatitis C.
N Engl J Med. 1998;3391485- 1492
Google ScholarCrossref 50.Shepherd
JWaugh
NHewitson
P Combination therapy (interferon alfa and ribavirin) in the treatment of chronic hepatitis C: a rapid and systematic review.
Health Technol Assess. 2000;41- 67
Google Scholar 51.Cummings
JLee
SMWest
ES
et al. Interferon and ribavirin vs interferon alone in the re-treatment of chronic hepatitis C previously nonresponsive to interferon: a meta-analysis of randomised trials.
JAMA. 2001;285193- 199
Google ScholarCrossref 52.Schalm
SWWeiland
OHansen
BE
et al. for the Eurohep Study Group for Viral Hepatitis, Interferon-ribavirin for chronic hepatitis C with and without cirrhosis: analysis of individual patient data of six controlled trials.
Gastroenterology. 1999;117408- 413
Google ScholarCrossref 53.Wong
JBPoynard
TLing
MHAlbrecht
JKPauker
SGfor the International Hepatitis Interventional Therapy Group, Cost-effectiveness of 24 or 48 weeks of interferon alpha-2b alone or with ribavirin as initial treatment of chronic hepatitis C.
Am J Gastroenterol. 2000;951524- 1530
Google Scholar 54.Wong
JBDavis
GLPauker
SG Cost-effectiveness of ribavirin/interferon alfa-2b after interferon relapse in chronic hepatitis C.
Am J Med. 2000;108366- 373
Google ScholarCrossref 55.Bennett
WGInoue
YBeck
JRWong
JBPauker
SGDavis
GL Estimates of the cost-effectiveness of a single course of interferon-alpha 2b in patients with histologically mild chronic hepatitis C.
Ann Intern Med. 1997;127855- 865
Google ScholarCrossref 56.Younossi
ZMSinger
MEMcHutchison
JGShermock
KM Cost effectiveness of interferon alpha-2b combined with ribavirin for the treatment of chronic hepatitis C.
Hepatology. 1999;301318- 1324
Google ScholarCrossref 57.Kim
WRPoterucha
JJHermans
JE
et al. Cost-effectiveness of 6 and 12 months of interferon-alpha therapy for chronic hepatitis C.
Ann Intern Med. 1997;127866- 874
Google ScholarCrossref 58.Wong
JB Cost-effectiveness of treatments for chronic hepatitis C.
Am J Med. 1999;107
((suppl))
74S- 78S
Google ScholarCrossref 59.Wong
JBKoff
RS Watchful waiting with periodic liver biopsy versus immediate empirical therapy for histologically mild chronic hepatitis C.
Ann Intern Med. 2000;133665- 675
Google ScholarCrossref 60.Sennfalt
KReichard
OHultkrantz
RWong
JBJonsson
D Cost-effectiveness of interferon alfa-2b with and without ribavirin as therapy for chronic hepatitis C in Sweden.
Scand J Gastroenterol. 2001;36870- 876
Google ScholarCrossref 61.Buti
MCasado
MAFosbrook
LWong
JBEsteban
R Cost-effectiveness of combination therapy for naive patients with chronic hepatitis C.
J Hepatol. 2000;33651- 658
Google ScholarCrossref 62.Sagmeister
MWong
JBMullhaupt
BRenner
EL A pragmatic and cost-effective strategy of a combination therapy of interferon alpha-2b and ribavirin for the treatment of chronic hepatitis C.
Eur J Gastroenterol Hepatol. 2001;13483- 488
Google ScholarCrossref 63.Kim
WRPoterucha
JJGross
JB
Jr Cost-effectiveness of interferon alfa 2b and ribavirin in the treatment of chronic hepatitis C.
Hepatology. 2000;31807- 808
Google ScholarCrossref 64.Zeuzem
SFeinman
VRasenack
J
et al. Peg-interferon alfa-2a in patients with chronic hepatitis C.
N Engl J Med. 2000;3431666- 1672
Google ScholarCrossref 65.Reddy
KWright
TLPockros
P
et al. Efficacy and safety of pegylated (40-kd) interferon alpha-2a compared with interferon alpha-2a in noncirrhotic patients with chronic hepatitis C.
Hepatology. 2001;33433- 438
Google ScholarCrossref 66.Glue
PFang
JWRouzier-Panis
R
et al. for the Hepatitis C Intervention Therapy Group, Pegylated interferon-alpha2b: pharmacokinetics, pharmacodynamics, safety, and preliminary efficacy data.
Clin Pharmacol Ther. 2000;68556- 567
Google ScholarCrossref 67.Glue
PRouzier-Panis
RRaffanel
C
et al. for the Hepatitis C Intervention Therapy Group, A dose-ranging study of pegylated interferon alfa-2b and ribavirin in chronic hepatitis C.
Hepatology. 2000;32647- 653
Google ScholarCrossref 68.Heathcote
J Antiviral therapy for patients with chronic hepatitis C.
Semin Liver Dis. 2000;20185- 199
Google ScholarCrossref 69.Lindsay
KTrepo
CHeintges
T
et al. A randomized, double-blind trial comparing pegylated interferon alfa-2b to interferon alfa-2b as initial treatment for chronic hepatitis C.
Hepatology. 2001;34395- 403
Google ScholarCrossref 70.Manns
MPMcHutchison
JGGordon
SC
et al. Peginterferon alfa-2b plus ribavirin compared with interferon alfa-2b plus ribavirin for initial treatment of chronic hepatitis C: a randomised trial.
Lancet. 2001;358958- 965
Google ScholarCrossref 71.Booth
JCO'Grady
JNeuberger
J Clinical guidelines on the management of hepatitis C.
Gut. 2001;49
((suppl 1))
I1- I21
Google ScholarCrossref 72.European Association for Study of the Liver, EASL International Consensus Conference on hepatitis C.
J Hepatol. 1999;31
((suppl 1))
3- 8
Google ScholarCrossref 73.Not Available, Recommendations for prevention and control of hepatitis C virus (HCV) infection and HCV-related chronic disease.
MMWR Morb Mortal Wkly Rep. 1998;47
((RR-19))
1- 39
Google Scholar 76.Sherman
KRouster
SDChung
RTRajicic
N Hepatitis C virus prevalence among patients infected with human immunodeficiency virus: a cross-sectional analysis of the US adult AIDS clinical trials Group.
Clin Infect Dis. 2002;34831- 837
Google ScholarCrossref 77.Gold
MRSiegel
JERussell
LBWeinstein
MC Cost-effectiveness in Health and Medicine. New York, NY Oxford University Press1996;
78.Centers for Disease Control and Prevention, 1999 USPHS/IDSA guidelines for the prevention of opportunistic infections in persons infected with human immunodeficiency virus.
MMWR Recomm Rep. 1999;48
((RR-10))
1- 5961- 66
Google Scholar 80.Mattson
LSönnerborg
AWeiland
O Outcome of acute symptomatic non-A, non-B hepatitis: a 13-year follow-up study of hepatitis C virus markers.
Liver. 1993;13274- 278
Google ScholarCrossref 81.Kao
JHTsai
SLChen
PJ
et al. A clinicopathologic study of chronic non-A, non-B (type C) hepatitis in Taiwan: comparison between posttransfusion and sporadic patients.
J Hepatol. 1994;21244- 249
Google ScholarCrossref 82.Seeff
LBBuskell-Bales
ZWright
EC
et al. for the National Heart, Lung, and Blood Institute Study Group, Long-term mortality after transfusion-associated non-A, non-B hepatitis.
N Engl J Med. 1992;3271906- 1911
Google ScholarCrossref 83.Pagliaro
LPeri
VLinea
CCamma
CGiunta
MMagrin
S Natural history of chronic hepatitis C.
Ital J Gastroenterol Hepatol. 1999;3128- 44
Google Scholar 84.Vaquer
PCanet
RLlompart
ARiera
JObrador
AGaya
J Histological evolution of chronic hepatitis C: factors related to progression.
Liver. 1994;14265- 269
Google ScholarCrossref 85.Yousuf
MNakano
YTanaka
ESodeyama
TKiyosawa
K Persistence of viremia in patients with type-C chronic hepatitis during long-term follow-up.
Scand J Gastroenterol. 1992;27812- 816
Google ScholarCrossref 86.Shev
SDhillon
APLindh
M
et al. The importance of cofactors in the histologic progression of minimal and mild chronic hepatitis C.
Liver. 1997;17215- 223
Google ScholarCrossref 87.Takahashi
MYamada
GMiyamoto
RDoi
TEndo
HTsuji
T Natural course of chronic hepatitis C.
Am J Gastroenterol. 1993;88240- 243
Google Scholar 88.Tremolada
FCasarin
CAlberti
A
et al. Long-term follow-up of non-A, non-B (type C) post-transfusion hepatitis.
J Hepatol. 1992;16273- 281
Google ScholarCrossref 89.Yano
MKumada
HKage
M
et al. The long-term pathological evolution of chronic hepatitis C.
Hepatology. 1996;231334- 1340
Google ScholarCrossref 90.Kobayashi
MTanaka
ESodeyama
TUrushihara
AMatsumoto
AKiyosawa
K The natural course of chronic hepatitis C: a comparison between patients with genotypes 1 and 2 hepatitis C viruses.
Hepatology. 1996;23695- 699
Google ScholarCrossref 91.Fattovich
GGiustina
GDegos
F
et al. Morbidity and mortality in compensated cirrhosis type C: a retrospective follow-up study of 384 patients.
Gastroenterology. 1997;112463- 472
Google ScholarCrossref 92.Christensen
EKrintel
JJHansen
SM
et al. Prognosis after the first episode of gastrointestinal bleeding or coma in cirrhosis: survival and prognostic factors.
Scand J Gastroenterol. 1989;24999- 1006
Google ScholarCrossref 93.Serfaty
LAumaître
HChazouillères
O
et al. Determinants of outcome of compensated hepatitis C virus–related cirrhosis.
Hepatology. 1998;271435- 1440
Google ScholarCrossref 94.Tsukuma
HHiyama
TTanaka
S
et al. Risk factors for hepatocellular carcinoma among patients with chronic liver disease.
N Engl J Med. 1993;3281797- 1801
Google ScholarCrossref 95.Gines
PQuintero
EArroyo
V
et al. Compensated cirrhosis: natural history and prognostic factors.
Hepatology. 1987;7122- 128
Google ScholarCrossref 96.Gentilini
PLaffi
GLa Villa
G
et al. Long course and prognostic factors of virus-induced cirrhosis of the liver.
Am J Gastroenterol. 1997;9266- 72
Google Scholar 97.Not Available, SEER Cancer Statistics Review, 1973-1994. Surveillance, Epidemiology, and End Results Web site. Available at:
http://www-seer.ims.nci.nih.gov/. Accessed July 7, 2001
98.Salerno
FBorroni
GMoser
P
et al. Survival and prognostic factors of cirrhotic patients with ascites: a study of 134 outpatients.
Am J Gastroenterol. 1993;88514- 519
Google Scholar 99.National Center for Health Statistics, Vital Statistics of the United States, 1992. Washington, DC Public Health Service1996;
100.Enger
CGraham
NPeng
Y
et al. Survival from early, intermediate, and late stages of HIV infection.
JAMA. 1996;2751329- 1334
Google ScholarCrossref 101.Freedberg
KALosina
EWeinstein
MC
et al. The cost effectiveness of combination antiretroviral therapy for HIV disease.
N Engl J Med. 2001;344824- 831
Google ScholarCrossref 102.Weinstein
MCGoldie
SJLosina
E
et al. Use of genotypic resistance testing to guide HIV therapy: clinical impact and cost-effectiveness.
Ann Intern Med. 2001;134440- 450
Google ScholarCrossref 103.Goldie
SJKaplan
JELosina
E
et al. Prophylaxis for human immunodeficiency virus–related
Pneumocystis carinii pneumonia: using simulation modeling to inform clinical guidelines.
Arch Intern Med 2002;162921- 928
Google ScholarCrossref 104.Not Available, Multicenter AIDS Cohort Study (MACS) Public Dataset: Release P04. Springfield, Va National Technical Information Service1995;
105.Longini
IJClark
WSByers
RH
et al. Statistical analysis of the stages of HIV infection using a Markov model.
Stat Med. 1989;8831- 843
Google ScholarCrossref 106.Patil
RCotler
SJBanaad-Omiotek
G
et al. Physicians' preference values for hepatitis C health states and antiviral therapy: a survey.
BMC Gastroenterol. 2001;1- 6
Google Scholar 107.Schackman
BRGoldie
SJFreedberg
KALosina
EBrazier
JWeinstein
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;2227- 38
Google ScholarCrossref 108.Bozzette
SABerry
SHDuan
N
et al. for the HIV Cost and Services Utilization Study Consortium, The care of HIV-infected adults in the United States.
N Engl J Med. 1998;3391897- 1904
Google ScholarCrossref 109.Torrance
GWFeeny
DHFurlong
WJBarr
RDZhang
YWang
Q Multiattribute utility function for a comprehensive health status classification system: Health Utilities Index Mark 2.
Med Care. 1996;34702- 722
Google ScholarCrossref 110.Brazier
JUsherwood
THarper
RThomas
K Deriving a preference-based single index from the UK SF-36 Health Survey.
J Clin Epidemiol. 1998;511115- 1128
Google ScholarCrossref 111.Foster
GRGoldin
RDThomas
HC Chronic hepatitis C virus infection causes a significant reduction in quality of life in the absence of cirrhosis.
Hepatology. 1998;27209- 212
Google ScholarCrossref 112.Foster
GR Hepatitis C virus infection: quality of life and side effects of treatment.
J Hepatol. 1999;31
((suppl 1))
250- 254
Google ScholarCrossref 113.Bonkovsky
HLWoolley
JMfor the Consensus Interferon Study Group, Reduction of health-related quality of life in chronic hepatitis C and improvement with interferon therapy.
Hepatology. 1999;29264- 270
Google ScholarCrossref 114.Ware
JEBayliss
MSMannocchia
MDavis
GL Health-related quality of life in chronic hepatitis C: impact of disease and treatment.
Hepatology. 1999;30550- 555
Google ScholarCrossref 115.Neary
MCort
SBayliss
MWare
JE
Jr Sustained virologic response is associated with improved health-related quality of life in relapsed chronic hepatitis C patients.
Semin Liver Dis. 1999;19
((suppl 1))
77- 85
Google Scholar 116.McHutchison
JWare
JEBayliss
MS
et al. The effects of interferon alpha-2b in combination with ribavirin on health-related quality of life and work productivity.
J Hepatol. 2001;34140- 147
Google ScholarCrossref 117.Younossi
ZBoparai
NMcCormick
MPrice
LGuyatt
G Assessment of utilities and health-related quality of life in patients with chronic liver disease.
Am J Gastroenterol. 2001;96579- 583
Google ScholarCrossref 118.Younossi
ZBoparai
NPrice
L
et al. Health-related quality of life in chronic liver disease: the impact of type and severity of disease.
Am J Gastroenterol. 2001;962199- 2205
Google ScholarCrossref 120.Fontana
RJMoyer
CASonnad
S
et al. Comorbidities and quality of life in patients with interferon-refractory chronic hepatitis C.
Am J Gastroenterol. 2001;96170- 178
Google ScholarCrossref 121.Rasenack
JZeuzem
SFeinman
S
et al. Therapy with pegylated interferon alfa-2a significantly enhances quality of life compared with standard interferon [abstract]. Paper presented at: the American Association for the Study of Liver Diseases October 27-31, 2000 Dallas, Tex
122.Treadwell
JRKearney
DDavila
M Health profile preferences of hepatitis C patients.
Dig Dis Sci. 2000;45345- 350
Google ScholarCrossref 123.Rodger
AJJolley
DThompson
SCLanigan
ACrofts
N The impact of diagnosis of hepatitis C virus on quality of life.
Hepatology. 1999;301299- 1301
Google ScholarCrossref 124.Hussain
KFontana
RJMCSu
GLSneed-Pee
NLok
AS Comorbid illness is an important determinant of health-related quality of life in patients with chronic hepatitis C.
Am J Gastroenterol. 2001;962737- 2744
Google ScholarCrossref 125.Wong
JBBennett
WGKoff
RSPauker
SG Pretreatment evaluation of chronic hepatitis C: risks, benefits, and costs.
JAMA. 1998;2802088- 2093
Google ScholarCrossref 126.Chong
C Health state utilities and quality of life in hepatitis C patients. Paper presented at: 23rd Annual Meeting of the Society for Medical Decision Making October 21-24, 2001 San Diego, Calif
127.Siebert
U Health related quality of life in chronic hepatitis C patients: a comparison of different utility assessment methods. Paper presented at: 23rd Annual Meeting of the Society for Medical Decision Making October 21-24, 2001 San Diego, Calif
128.Not Available, 2000 Drug Topics: Red Book. Montvale, NJ Medical Economics2000;
129.Bureau of Labor Statistics, Statistical Abstract of the United States: Consumer Price Index—All Urban Consumers. Washington, DC Bureau of the Census2000;
130.Wong
JBMcQuillan
GMMcHutchison
JGPoynard
T Estimating future hepatitis C morbidity, mortality, and costs in the United States.
Am J Public Health. 2000;901562- 1569
Google ScholarCrossref 132.AIDS treatment data network, Hepatitis C Action and Advocacy Coalition Web site. Available at:
http://www.atdn.org. Accessed December 28, 2001
133.Shiell
ABriggs
AFarrell
GC The cost effectiveness of alpha interferon in the treatment of chronic active hepatitis C.
Med J Aust. 1994;160268- 272
Google Scholar 134.Not Available, 2000 Clinical Diagnostic Laboratory Fee Schedule Public Use File. Baltimore, MD Health Care Financing Administration2000;
135.Bozzette
SAJoyce
GMcCaffrey
DF
et al. Expenditures for the care of HIV-infected patients in the era of highly active antiretroviral therapy.
N Engl J Med. 2001;344817- 823
Google ScholarCrossref 136.Not Available, AIDS Cost and Services Utilization Survey: Public Use Tapes 4 and 5. Springfield, Va National Technical Information Service1994;No. PB94189891
137.Holtgrave
DRPinkerton
SD Updates of cost of illness and quality of life estimates for use in economic evaluations of HIV prevention programs.
J Acquir Immune Defic Syndr Hum Retrovirol. 1997;1654- 62
Google ScholarCrossref 138.Goldie
SJWeinstein
MCKuntz
KMFreedberg
KA The costs, clinical benefits, and cost-effectiveness of screening for cervical cancer in HIV-infected women.
Ann Intern Med. 1999;13097- 107
Google ScholarCrossref 139.Tradati
FColombo
MMannucci
PM
et al. for the Study Group of the Association of Italian Hemophilia Centers, A prospective multicenter study of hepatocellular carcinoma in Italian hemophiliacs with chronic hepatitis C.
Blood. 1998;911173- 1177
Google Scholar 140.Boyer
NMarcellin
PDegott
C
et al. Recombinant interferon-alpha for chronic hepatitis C in patients positive for antibody to human immunodeficiency virus.
J Infect Dis. 1992;165723- 726
Google ScholarCrossref 141.Causse
XPayen
JLIzopet
JBabany
GGirardin
MFfor the French Multicenter Study Group, Does HIV-infection influence the response of chronic hepatitis C to interferon treatment? a French multicenter prospective study.
J Hepatol. 2000;321003- 1010
Google ScholarCrossref 142.Garcia-Samaniego
JSoriano
VBravo
B
et al. Efficacy and safety of alpha interferon therapy for chronic hepatitis C in HIV patients [abstract].
Hepatology. 1994;20162A
Google Scholar 143.Hanley
JPJarvis
LMAndrew
J
et al. Interferon treatment for chronic hepatitis C infection in hemophiliacs: influence of virus load, genotype, and liver pathology on response.
Blood. 1996;871704- 1709
Google Scholar 144.Landau
ABatisse
DVan Huyen
JP
et al. Efficacy and safety of combination therapy with interferon-alpha2b and ribavirin for chronic hepatitis C in HIV-infected patients.
AIDS. 2000;14839- 844
Google ScholarCrossref 145.Mauss
SHeintges
TAdams
O
et al. Treatment of chronic hepatitis C with interferon-alpha in patients infected with the human immunodeficiency virus.
Hepatogastroenterology. 1995;42528- 534
Google Scholar 146.Perez-Olmeda
MGonzalez
JGarcia-Samaniego
J
et al. Interferon + ribavirin in HIV+ patients with chronic hepatitis C. Paper presented at: 7th Conference on Retroviruses and Opportunistic Infections January 30-Feberuary 2, 2000 San Francisco, CalifAvailable at:
http://www.retroconference.org/2000/abstracts/284.htm. Accessed April 23, 2001. Abstract 284
147.Soriano
VNedjar
SGarcia-Samaniego
J
et al. for the Hepatitis HIV Spanish Study Group, High rate of co-infection with different hepatitis C virus subtypes in HIV-infected intravenous drug addicts in Spain.
J Hepatol. 1995;22598- 599
Google ScholarCrossref 148.Zylberberg
HBenhamou
YLagneaux
J
et al. Safety and efficacy of interferon-ribavirin combination therapy in HCV-HIV coinfected subjects: an early report.
Gut. 2000;47694- 697
Google ScholarCrossref 149.Yano
M Advances in hepatitis C: sero-epidemiology and natural history.
J Gastroenterol Hepatol. 1992;7549- 550
Google ScholarCrossref 150.Kiyosawa
KSodeyama
TTanaka
E
et al. Interrelationship of blood transfusion, non-A, non-B hepatitis and hepatocellular carcinoma: analysis by detection of antibody to hepatitis C virus.
Hepatology. 1990;12671- 675
Google ScholarCrossref 151.Niederau
CLange
SHeintges
T
et al. Prognosis of chronic hepatitis C: results of a large, prospective cohort study.
Hepatology. 1998;281687- 1695
Google ScholarCrossref 152.Tong
MJEl-Farra
NSReikes
ARCo
RL Clinical outcomes after transfusion-associated hepatitis C.
N Engl J Med. 1995;3321463- 1466
Google ScholarCrossref 153.Gordon
SCElloway
RSLong
JCDmuchowski
CF The pathology of hepatitis C as a function of mode of transmission: blood transfusion vs intravenous drug use.
Hepatology. 1993;181338- 1343
Google ScholarCrossref 154.Hopf
UMoller
BKuther
D
et al. Long-term follow-up of posttransfusion and sporadic chronic hepatitis non-A, non-B and frequency of circulating antibodies to hepatitis C virus (HCV).
J Hepatol. 1990;1069- 76
Google ScholarCrossref 155.Koretz
RLBrezina
MPolito
AJ
et al. Non-A, non-B posttransfusion hepatitis: comparing C and non-C hepatitis.
Hepatology. 1993;17361- 365
Google ScholarCrossref 157.Kenny-Walsh
Eand the Irish Hepatology Research Group, Clinical outcomes after hepatitis C infection from contaminated anti-D immune globulin.
N Engl J Med. 1999;3401228- 1233
Google ScholarCrossref 159.Seeff
LBMiller
RNRabkin
CS
et al. 45-Year follow-up of hepatitis C virus infection in healthy young adults.
Ann Intern Med. 2000;132105- 111
Google ScholarCrossref 160.Sabin
CTelfer
PPhillips
ABhagani
SLee
C The association between hepatitis C virus genotype and human immunodeficiency virus disease progression in a cohort of hemophilic men.
J Infect Dis. 1997;175164- 168
Google ScholarCrossref 161.Romeo
RRumi
MGDonato
F
et al. Hepatitis C is more severe in drug users with human immunodeficiency virus infection.
J Viral Hepat. 2000;7297- 301
Google ScholarCrossref 162.Makris
MPreston
FRosendaal
FUnderwood
JRice
KTriger
D The natural history of chronic hepatitis C in haemophiliacs.
Br J Haematol. 1996;94746- 752
Google ScholarCrossref 163.Pol
SZylberberg
H Interactions between the human immunodeficiency virus and hepatitis C virus.
Rev Med Interne. 1998;19885- 891
Google ScholarCrossref 164.Staples
CT
JrRimland
DDudas
D Hepatitis C in the HIV (human immunodeficiency virus) Atlanta VA (Veterans Affairs Medical Center) Cohort Study (HAVACS): the effect of coinfection on survival.
Clin Infect Dis. 1999;29150- 154
Google ScholarCrossref 165.Goldie
SJKuntz
KMWeinstein
MCFreedberg
KAPalefsky
JM Cost-effectiveness of screening for HPV-induced anal squamous intraepithelial lesions in homosexual men.
Am J Med. 2000;108634- 641
Google ScholarCrossref 166.Staszewski
SMorales-Ramirez
JTashima
KT
et al. for the Study 006 Team, Efavirenz plus zidovudine and lamivudine, efavirenz plus indinavir, and indinavir plus zidovudine and lamivudine in the treatment of HIV-1 infection in adults.
N Engl J Med. 1999;3411865- 1873
Google ScholarCrossref 167.Hammer
SMSquires
KEHughes
MD
et al. for the AIDS Clinical Trials Group 320 Study Team, A controlled trial of two nucleoside analogues plus indinavir in persons with human immunodeficiency virus infection and CD4 cell counts of 200 per cubic millimeter or less.
N Engl J Med. 1997;337725- 733
Google ScholarCrossref 168.Baxter
JDMayers
DLWentworth
DN
et al. for the CPCRA 046 Study Team for the Terry Beirn Community Programs for Clinical Research on AIDS, A randomized study of antiretroviral management based on plasma genotypic antiretroviral resistance testing in patients failing therapy.
AIDS. 2000;14F83- F93
Google ScholarCrossref 169.Lucas
GMChaisson
REMoore
RD Highly active antiretroviral therapy in a large urban clinic: risk factors for virologic failure and adverse drug reactions.
Ann Intern Med. 1999;13181- 87
Google ScholarCrossref 170.Gulick
RMMellors
JWHavlir
D
et al. Simultaneous vs sequential initiation of therapy with indinavir, zidovudine, and lamivudine for HIV-1 infection: 100-week follow-up.
JAMA. 1998;28035- 41
Google ScholarCrossref 171.Montaner
JSReiss
PCooper
D
et al. A randomized, double-blind trial comparing combinations of nevirapine, didanosine, and zidovudine for HIV-infected patients: the INCAS Trial: Italy, The Netherlands, Canada and Australia Study.
JAMA. 1998;279930- 937
Google ScholarCrossref 172.Sulkowski
MSThomas
DLChaisson
REMoore
RD Hepatotoxicity associated with antiretroviral therapy in adults infected with human immunodeficiency virus and the role of hepatitis C or B virus infection.
JAMA. 2000;28374- 80
Google ScholarCrossref 174.Monforte
AAde
ABugarini
R
et al. Low frequency of severe hepatotoxicity and association with HCV coinfection in HIV-positive patients treated with HAART.
J Acquir Immune Defic Syndr. 2001;28114- 123
Google ScholarCrossref 175.den Brinker
MWit
FWWertheim-van
PM
et al. Hepatitis B and C virus co-infection and the risk for hepatotoxicity of highly active antiretroviral therapy in HIV-1 infection.
AIDS. 2000;142895- 2902
Google ScholarCrossref 176.Rodriguez-Rosado
RJimenez-Nacher
ISoriano
VAnton
PGonzalez-Lahoz
J Virological failure and adherence to antiretroviral therapy in HIV-infected patients.
AIDS. 1998;121112- 1113
Google ScholarCrossref 177.Melvin
DLee
JBelsey
EArnold
JMurphy
R The impact of co-infection with hepatitis C virus and HIV on the tolerability of antiretroviral therapy.
AIDS. 2000;14463- 465
Google ScholarCrossref 178.Servoss
JSherman
KERobbins
G
et al. Hepatotoxicity in the US Adult AIDS Clinical Trial Group [abstract].
Gastroenterology. 2001;120- 283
Google Scholar 179.Roychowdhury
A The impact of HIV therapy with HAART on HCV disease in HIV/HCV co-infection. Paper presented at: Digestive Disease Week 2001 conference May 20-23, 2001 Atlanta, GaAbstract 1894
182.Max
BSherer
R Management of the adverse effects of antiretroviral therapy and medication adherence.
Clin Infect Dis. 2000;30
((suppl 2))
S96- S116
Google ScholarCrossref 183.Filippini
PCoppola
NScolastico
C
et al. Can HCV affect the efficacy of anti-HIV treatment?
Arch Virol. 2000;145937- 944
Google ScholarCrossref 184.Torre
DTambini
RCFBarbarini
GMoroni
MBasilico
C Evolution of coinfection with human immunodeficiency virus and hepatitis C virus in patients treated with highly active antiretroviral therapy.
Clin Infect Dis. 2001;331579- 1585
Google ScholarCrossref 185.Esnaola
N Comparison of addictive and multiplicative utility functions to predict the utilities of combined health states. Paper presented at: 23rd Annual Meeting of the Society for Medical Decision Making October 21-24, 2001 San Diego, Calif
186.Zaric
GSBarnett
PGBrandeau
ML HIV transmission and the cost-effectiveness of methadone maintenance.
Am J Public Health. 2000;901100- 1111
Google ScholarCrossref 187.Torrance
GW Social preferences for health states: an empirical evaluation of three measurement techniques.
Socioecon Planning Sci. 1976;10128- 136
Google Scholar 188.Hunt
CMDominitz
JABute
BPWaters
BBlasi
UWilliams
DM Effect of interferon-alpha treatment of chronic hepatitis C on health-related quality of life.
Dig Dis Sci. 1997;422482- 2486
Google ScholarCrossref 189.Davis
GLBalart
LASchiff
ER
et al. Assessing health related quality of life in chronic hepatitis C using the sickness impact profile.
Clin Ther. 1994;16334- 343
Google Scholar