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Logo of nihpaAbout Author manuscriptsSubmit a manuscriptHHS Public Access; Author Manuscript; Accepted for publication in peer reviewed journal;
 
Int J Infect Dis. Author manuscript; available in PMC 2010 July 1.
Published in final edited form as:
PMCID: PMC2731415
NIHMSID: NIHMS128833

Effect of race and HIV co-infection upon treatment prescription for hepatitis C virus

Summary

Background:

Treatment rates for hepatitis C virus (HCV) have not been compared directly between HCV mono-infected and HCV–HIV co-infected patients in academic center settings.

Methods:

We prospectively enrolled consecutive mono-infected and co-infected subjects at three academic centers in the USA. Clinical and laboratory data were gathered through interviews and medical records. Logistic regression analysis was used to determine the factors associated with treatment prescription for HCV.

Results:

The 241 HCV mono-infected and 158 HCV–HIV co-infected subjects were similar in age, but there were more blacks (58.9% vs. 30.7%, p < 0.001) and males (81.6% vs. 58.5%, p < 0.001) in the latter group. The co-infected subjects were less likely to have a liver biopsy (43.7% vs. 71.4%, p < 0.001) or ever receive treatment for HCV (32.3% vs. 62.2%, p < 0.001). In bivariate analysis, subjects not prescribed treatment for HCV were more likely to be black, have HIV co-infection, and have ongoing alcohol abuse. In multivariate analysis, black race (odds ratio (OR) 0.44, 95% confidence interval (CI) 0.28–0.70) and HIV co-infection (OR 0.33, 95% CI 0.21–0.53) were independently associated with non-prescription of treatment.

Conclusions:

Black race and HIV co-infection are associated with a lower likelihood of treatment for HCV. Addressing comorbidities in these populations may help to reduce such treatment disparities.

Keywords: Hepatitis C virus, HIV, Co-infection, Treatment rates, Racial disparity

Introduction

The last decade has seen significant advances in therapies for hepatitis C virus (HCV). With currently available pharmacotherapy, sustained virologic response rates range from 54% to 56% in HCV mono-infected persons and from 27% to 40% in HCV–HIV co-infected persons.1-5 Despite these successes, few data exist on the rates of HCV treatment and factors associated with non-treatment among HCV mono-infected and HCV–HIV co-infected individuals. Studies have been conducted primarily among patients receiving care at Veterans Affairs (VA) medical centers, where access to HCV treatment is not dependent on reimbursement issues,6-9 but this patient population is demographically and socio-economically different than the general population. Among HCV-infected patients at VA healthcare facilities, HCV treatment prescription rates are low in both HCV–HIV co-infected and HCV mono-infected persons.7,8 For veterans in care at the VA facilities, non-treatment is associated with certain medical, psychiatric, and substance abuse comorbidities, conditions that are more prevalent in this population than in the general population. To our knowledge, there has been no direct comparison of HCV mono-infected and HCV–HIV co-infected persons to determine the differences in treatment rates and factors associated with non-treatment in a non-VA setting. To address these issues, we conducted this study to determine and directly compare the rates of treatment and reasons for non-treatment for HCV in HCV mono-infected vs. HCV–HIV co-infected persons in non-VA academic medical center settings. These results may suggest future interventions to increase prescription rates of antiviral therapy, which can help to lower the incidence of HCV-associated liver failure in the HCV mono-infected and HCV–HIV co-infected populations.

Methods

We performed a cross-sectional study among prospectively recruited adult HCV mono-infected and HCV–HIV co-infected patients referred for HCV care to the infectious diseases/HIV clinics and hepatology clinics of the University of Pittsburgh Medical Center in Pittsburgh, PA, University of Pennsylvania Medical Center in Philadelphia, PA, and the University of Cincinnati Medical Center in Cincinnati, OH. Inclusion criteria included (1) a positive test for anti-HCV antibody, and (2) at least one visit for HCV care. Patients were placed in the HCV–HIV co-infected group if, in addition, they had a positive test for anti-HIV antibody and/or detectable HIV RNA. Eligible subjects were identified at all sites through computerized registries, and all subjects seen between January 2005 and November 2006 were offered inclusion in this study.

After obtaining informed consent, we interviewed all subjects using a standard questionnaire to gather information on demographics, risk factors for HCV and HIV, comorbid illnesses, substance abuse (tobacco, alcohol, and illicit drugs as reported by subjects), educational status, history of incarceration, and number of lifetime sexual partners. We abstracted additional laboratory and clinical data from subject medical records at the initial and most recent visits for HCV care. Liver biopsy data were retrieved from hospital computerized pathology records, where they were recorded as modified histology activity index (HAI) score. Necroinflammatory (inflammation) and fibrosis scores were retrieved from the histopathology report and recorded separately. HCV treatment information was gathered from patient self-report and confirmed by chart and/or pharmacy records review. The study was approved by the institutional review boards of the University of Pittsburgh (ClinicalTrials.gov identifier NCT00222859), University of Pennsylvania, and University of Cincinnati.

Our primary outcome measure was prescription of treatment for HCV at any past time, determined from subject self-report and pharmacy records at each site. Subjects were considered to have been prescribed HCV treatment if any prescription for interferon-alpha or pegylated interferon-alpha (with or without ribavirin) was written for the patient at any time point, for any duration. Anemia was defined as a hemoglobin level ≤13.0 g/dl for men and ≤12.0 g/dl for women, neutropenia was defined as a total leukocyte count <1.5 × 109 cells/l, and thrombocytopenia was defined as a platelet count <75 × 109/l (all at first HCV care visit) (Table 1).

Table 1
Summary of definitions used for the study

Baseline subject characteristics were described by using means and standard deviations for continuous data and proportions for categorical data. Differences between groups were assessed by using t-tests or Wilcoxon rank-sum tests, as appropriate, for continuous data and Chi-square or Fisher's exact tests for categorical data. Factors associated with treatment prescription were tested first in univariate logistic regression models. Stepwise multivariate logistic regression was then performed retaining variables that were significant at p < 0.10 in the univariate model. All analyses were conducted using STATA® statistical software (Stata Corporation, College Station, TX, USA). Given our sample sizes for the two groups and a two-tailed alpha of 0.05, we had 80% power to detect the following differences in treatment prescription rates between the HCV–HIV co-infected patients and the HCV mono-infected patients, respectively: 0.20 vs. 0.33; 0.25 vs. 0.38; 0.30 vs. 0.44, and 0.35 vs. 0.49.

Results

We recruited a total of 399 subjects (241 HCV mono-infected and 158 HCV–HIV co-infected). The two groups were similar in age, but there were more blacks (58.9% vs. 30.7%, p < 0.001) and males (81.6% vs. 58.5%, p < 0.001) in the HCV–HIV co-infected group (Table 2). HCV–HIV co-infected subjects also had a lower mean (SD) body mass index compared with the HCV mono-infected subjects (25.8 (5.5) vs. 29.1 (5.6), p < 0.001).

Table 2
Baseline characteristics of HCV mono-infected and HCV–HIV co-infected subjects

A total of 241 subjects (60.4%) underwent liver biopsy. HCV–HIV co-infected subjects were less likely to have a liver biopsy performed than HCV mono-infected subjects (43.7% vs. 71.4%, p < 0.001). The HCV–HIV co-infected patients had lower mean (SD) fibrosis scores (2.1 (1.3) vs. 2.5 (1.5), p = 0.04) and inflammation scores (2.6 (1.6) vs. 3.7 (2.0), p = 0.001) compared to HCV mono-infected subjects (Table 2).

A total of 201 subjects (50.4%) were ever prescribed HCV therapy. HCV–HIV co-infected subjects were less likely to have ever initiated treatment for HCV than HCV mono-infected subjects (32.3% vs. 62.2%, p < 0.001). In addition, subjects not prescribed treatment were more likely to be of black race, HIV co-infected, and have ongoing alcohol abuse (Table 3).

Table 3
Characteristics of subjects prescribed treatment for HCV vs. those who were not prescribed treatment for HCV

When we examined factors associated with non-receipt of HCV therapy separately among HCV mono-infected and HCV–HIV co-infected subjects, fewer subjects of black race were prescribed treatment in each group (though the difference did not reach statistical significance in the HCV–HIV co-infected group) (Table 4). In univariate analysis, black race (odds ratio (OR) 0.39, 95% confidence interval (CI) 0.26–0.59), HIV co-infection (OR 0.29, 95% CI 0.19–0.44), and ongoing alcohol abuse (OR 0.53, 95% CI 0.30–0.89) were associated with a lesser likelihood of receiving treatment for HCV (Table 5). In multivariate analysis, black race (adjusted OR 0.44, 95% CI 0.28–0.70) and HIV co-infection (adjusted OR 0.33, 95% CI 0.21–0.53) were associated with a lower likelihood of treatment prescription, while anemia was associated with an increased likelihood of treatment prescription (adjusted OR 2.16, 95% CI 1.26–3.70) (Table 6). When we analyzed the HCV mono-infected and HCV–HIV co-infected groups separately, black race was associated with a lower likelihood of receiving treatment in each group, with a lower odds ratio in the latter group compared with the former.

Table 4
A comparison of subjects prescribed treatment for HCV with those who were not prescribed treatment by HIV status
Table 5
Factors associated with treatment prescription for HCV (univariate logistic regression)
Table 6
Factors associated with treatment prescription for HCV (multivariate logistic regression)a

Subjects who were HCV–HIV co-infected were more likely to have at least one comorbidity compared with HCV mono-infected subjects (80.4% vs. 63.9%, p < 0.001; results not shown). The following comorbidities/contraindications were more likely to be present in blacks (p < 0.05): diabetes, autoimmune disease, intravenous drug use, and anemia prior to treatment. Blacks were also more likely to have at least one comorbidity compared to non-blacks, but this did not reach statistical significance (74.2% vs. 67.7%, p = 0.16).

Discussion

Our study demonstrates that there are significant differences in rates of treatment prescription for HCV between HCV mono-infected and HCV–HIV co-infected persons. HIV co-infection is an independent predictor of not receiving treatment for HCV. This effect persists even after adjusting for age, minority race, and other comorbidities. Such an effect has been demonstrated previously in veterans in care with HCV infection,8 but has not been shown in patients presenting to university medical centers. While HIV infection is not a contraindication for treatment for HCV, there are several possible reasons for this disparity. The response to currently available pharmacotherapy for HCV is lower in the HCV–HIV co-infected persons than in HCV mono-infected persons.4,5,10 Persons with HCV–HIV co-infection are more likely to have medical, psychiatric, and substance abuse comorbidities that could reduce HCV treatment eligibility.8,11,12 In addition, the majority of HCV–HIV co-infected patients receive complex antiretroviral drug regimens with potential drug interactions with ribavirin.13 Due to such factors, healthcare providers may be reluctant to initiate treatment for HCV in HCV–HIV co-infected persons. Whether other provider factors, e.g., provider level of comfort in prescribing anti-HCV therapy, knowledge, attitudes, and beliefs regarding HCV infection play any part in treatment decisions for HCV is unknown.

We also found that blacks are less likely to receive treatment for HCV than whites. Racial disparities have been observed for other treatment modalities.14-16 Among the HCV-infected, patients of black race are less likely to achieve a sustained virologic response compared with white patients.17,18 The reason for these differences is not known, but these data might affect provider decisions regarding treatment prescription for HCV in blacks. Additionally, prevalence of certain medical and psychiatric comorbidities and substance abuse rates are higher in blacks,19 and these represent additional barriers to prescription of HCV treatment.

Only a small number of HCV-infected persons in our study ever underwent a liver biopsy, despite being evaluated at tertiary care referral centers. HCV–HIV co-infected persons were less likely to undergo liver biopsy compared with HCV mono-infected persons. This might be due to provider reluctance to perform an invasive procedure in HCV–HIV co-infected patients who are more likely to have concomitant comorbidities and a reduced likelihood of achieving a sustained virologic response. The very low rate of obtaining a liver biopsy in the HCV–HIV co-infected patients (36.4%) suggests that noninvasive tests to assess hepatic fibrosis, either by use of serum markers (e.g., AST-to-platelet ratio index, FIB-4, SHASTA, or FibroSURE) or imaging modalities (e.g., elastometry) may be of value in this population.20 These tests, currently still under investigation, represent an alternative to the liver biopsy. Examination of the liver biopsy results in our study demonstrated lower mean necroinflammatory and fibrosis scores among HCV–HIV co-infected subjects compared with HCV mono-infected subjects. Since liver damage due to HCV is immunologically mediated, one plausible explanation is that the co-infected subjects had lesser damage due to a relatively suppressed immune system.

Our study has some limitations. It may not be representative of the HCV-infected population in general due to a likely referral bias. It is plausible that the patients referred to tertiary care centers are believed to be better candidates for HCV therapy by their primary care providers, implying that the treatment prescription rates in the general population may be even lower than what we found in our study. The laboratory data were not collected at predetermined study points, and were retrieved from the results routinely performed for clinical care of the patients. Furthermore, the liver biopsy results were read by different pathologists. The strengths of our study include prospective and uniform data collection. To our knowledge, ours is the first study to directly compare HCV treatment rates in the HCV mono-infected and HCV–HIV co-infected subjects receiving care at academic medical centers.

In conclusion, we found substantial disparities in the treatment of HCV. Blacks and HCV–HIV co-infected persons are less likely to receive treatment for HCV than whites or HCV mono-infected persons. Part of this disparity may be explained by the differences in comorbidities in blacks and those with HIV co-infection. Addressing comorbidities may help reduce this disparity in treatment.

Acknowledgments

Dr Butt is supported by a Career Development Award from the National Institutes of Health/National Institute on Drug Abuse (1 K23 DA016175-01A1). This study was also partly supported through grants from the Agency for Healthcare Quality and Research (1 R03 HS13220-01), the Health Services Research and Development Service, Department of Veterans Affairs (ECI 01-195), the National Center for Complementary and Alternative Medicine (1 R01 AT01147), and the National Institute of Allergy and Infectious Diseases (U01 AI 25897). Dr Tsevat is supported by a National Center for Complementary and Alternative Medicine award (grant # K24 AT001676). Dr Lo Re is supported by a Career Development Award from the National Institutes of Health/National Institute for Allergy and Infectious Diseases (K01 AI070001-01A1).

Footnotes

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Conflict of interest: No conflict of interest to declare.

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