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Psychiatric illness and illicit drugs as barriers to hepatitis C treatment
among HIV/hepatitis C virus co-infected individuals
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This article in the journal AIDS discusses how it is imperative to treat HCV-infected individuals who acquired HCV through IVDU. IVDU is the most common route of transmission for HCV accounting for perhaps 60% or more of new cases. The authors emphasize that we need to find ways to treat IV drug users. Clearly, IVDUs and other HCV-infected individuals present unique barriers to care including problems with depression, history of drug use, and additional emotional psychiatric illnesses. The authors also emphasize that we can successfully treat IVDUs with multi-disciplinary support services. I have been emphasizing this as well for some time. And there have been reports at recent hepatitis and liver conferences (AASLD, Nov 2002) outlining various such approaches to treating IVDUs successfully. Here is a link to my report on the presentations at AASLD. Jules Levin, NATAP
www.natap.org/2002/AASLD/day20.htm
Dr Guglielmo Nasti and colleagues [1] showed that combination treatment with IFN--2b/ribavirin could be well tolerated in HIV/hepatitis C virus (HCV) co-infected patients [1]. It has been customary to exclude from HCV treatment
patients with depression or active addiction, given concerns about psychiatric decompensation and the complications of injection drug use (IDU), including poor adherence and re-infection with HCV post-treatment. All the patients reported on by Nasti et al. [1] had addiction histories, although none were active drug abusers or were on methadone maintenance. Also, although they excluded patients with severe depression, Nasti and colleagues [1] did not include a psychiatric evaluation at baseline, thereby not excluding patients with milder forms of depression or other less obvious psychiatric disorders. Even with these somewhat less restrictive inclusion criteria, Nasti et al. [1] did not report side-effects of mood disturbances or complications of IDU among 17 patients co-infected with HIV/HCV through IDU. These findings hold important implications for the treatment of HCV in co-infected patients.
As a result of shared routes of transmission, co-infection with HIV and HCV is common, with rates as high as 80-90% in some populations [2]. Recent studies have shown that the disease course of HCV is accelerated in those individuals
with HIV [3]. Bica et al. [4] recently reported that the leading cause of death in their HIV-seropositive population was end-stage liver disease, with 94% of patients tested having antibodies to HCV. It is therefore vital that co-infected patients be treated for HCV. However, we have had difficulty enrolling co-infected patients in an HCV treatment trial because of restrictive exclusion criteria. Of 51 patients screened for eligibility to participate in an HCV treatment study, only five enrolled. The reasons for non-enrollment were recorded and analysed, and the breakdown is shown in Table 1.
These results are important for co-infected patients seeking treatment. Almost one-third of our patients were excluded because of mental illness, in particular severe depression. This is not surprising, given that that there is a higher rate of HCV among psychiatric populations, and those infected with HCV have a higher prevalence of depression [5]. Furthermore, IDU is now the major route of HCV transmission, and injection drug users are at increased risk of
depression [6]. Interferon has been associated with depression and suicidality [7]. Therefore, despite recent advances in
HCV treatment, concerns about the side-effects of interferon in co-infected patients have limited their treatment options.
Equally important, one-fifth of the patients did not enroll in the trial because of active addiction issues. The National Institutes of Health recommended that the treatment of HCV be withheld until patients had not injected illicit drugs for 6 months [8]. However, injection drug users comprise the reservoir of individuals from which most HCV spread occurs in the United States, making disease prevention and treatment of HCV in this population a public health imperative. Addiction is a chronic illness; therefore, waiting until addiction is ÔcuredÕ before initiating HCV treatment is unrealistic and places co-infected patients at risk of HCV disease progression [9].
The data of Nasti et al. [1] provide additional encouragement that co-infected patients can be treated with interferon, even in the face of addiction histories and potential psychiatric co-morbidities. In our patient population, the high prevalence of psychiatric illness and addiction suggests the need for the development of a multidisciplinary treatment and support program to see patients through treatment, and the development of alternative medications to treat HCV.
We support evaluating patients on a case-by-case basis. A growing body of evidencence shows that interventions to address the psychosocial difficulties of patients, including addiction, lack of support, and homelessness, can improve
adherence and help Injection drug users care for their health. The support of a healthcare team and open discussion of injecting behaviors can lead to healthier behaviors and increased adherence to medical visits [10]. Harm reduction and concurrent substance abuse treatment may also be helpful.
Finally, 26% of our patients chose not to participate because of the rigorous treatment regime and time commitment. In addition to issues of mental health and addiction, the many possible side-effects of interferon/ribavirin and the need for 24-48 weeks of therapy can limit interest and adherence in co-infected patients [11]. In the study by Nasti et al. [1], 16 out of 17 patients (94%) completed 6 monthsÕ of combination therapy without difficulty. This is inspiring to patients and physicians wanting to initiate therapy.
In summary, the study by Nasti et al. [1] provided reassurance that co-infected patients can safely be treated for HCV. It is time for more inclusive HCV treatment. Regarding the disappointingly low sustained response rate, treatment with pegylated interferon/ribavirin appears to hold promise, as does 48 rather than 24 weeks of treatment [12,13].
AIDS 2002;16:1700-1701
Lynn E. Taylor, Theresa Costello, Elizabeth Alt, Gail Yates, Karen Tashima
Department of Medicine and bCenters for Behavioral and Preventive Medicine, Brown Medical School, The Miriam Hospital, Providence, RI, USA.
References
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2.Dietrich DT. Hepatitis C virus and human immunodeficiency virus: clinical issues.Am J Med 1999,107 (Suppl.):79-84.
3.Sulkowski M,Mast E,Seeff. et al. Hepatitis C virus infection as an opportunistic disease in persons infected with human immunodeficiency virus.Clin Infect Dis 2000,30 (Suppl. 1):S77-S84.
4.Bica I,McGovern B,Dhar R,Stone D,McGowan K,Scheib R,Snydman D. Increasing mortality due to end-stage liver disease in patients with HIV.Clin Infect Dis 2001,32:492-497.
5.Zdilar D,Franco-Bronson K,Buchler N,Locala JA,Younossi ZM. Hepatitis C, interferon alfa, and depression.Hepatology 2000,31:1207-1211.
6.Knowlton AR,Latkin CA,Schroeder JR,Hoover DR,Ensminger M,Celentano DD. Longitudinal predictors of depressive symptoms among low income injection drug users.AIDS Care 2001,13:549-559.
7.Yates WR,Gleason O. Hepatitis C and depression.Depression Anxiety 1998,7:188-193.
8.National Institutes of Health. Management of hepatitis C. Consensus Statement, Vol. 15, No. 3. National Institutes of Health, Bethesda, MD; 1997.
9.Edlin B,Seal K,Lorvick J,Kral A,Ciccarone D,Moore L,Lo B. Is it justifiable to withhold treatment for hepatitis c from illicit-drug users? N Engl J Med 2001,345:211-214.
10.Rich JD,Macalino GE,McKenzie M,Taylor LE,Burris S. Syringe prescription to prevent HIV infection in Rhode Island: a case study.Am J Pub Health 2001,91:699-700.
11.Bruno R,Sacchi P,Filice C. Aggressive daily interferon therapy in HIV-HCV coinfected patients [Letter].J Acquired Immune Defic Syndr 2000,25:372-373.
12.Heathcote EJ,Shiffman ML,Cooksley WG.et al. Peginterferon alfa-2a in patients with chronic hepatitis C and cirrhosis.N Engl J Med 2000,343:1673-1680.
13.Zeuzem S,Feinman SV,Rasenack J.et al. Peginterferon alfa-2a in patients with chronic hepatitis C.N Engl J Med 2000,343:1666-1672.
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