In the era of highly effective antiretroviral therapy, infection with Hepatitis C virus (HCV) resulting in end-stage liver disease is one of the leading causes of mortality for HIV-infected persons in the developed world [1
]. Given the potential to eradicate HCV with antiviral therapy, HIV/HCV-co-infected persons are increasingly being treated for Hepatitis C.
Treatment outcomes are worse in HIV/HCV-co-infected patients as compared to HCV mono-infected patients: sustained virologic response (SVR) is achieved in up to 55% of HCV mono-infected and in up to 40% of HCV/HIV-co-infected patients [4
]. A research synthesis using meta-regression of seven PEG-IFN/RBV treatment studies in a total of 784 HCV/HIV-co-infected patients reported an overall SVR rate of 33% [10
There are high rates of current and past psychiatric and substance use disorders in the HIV/HCV-co-infected population [11
]. This substantively complicates the treatment of HCV with pegylated interferon alfa and ribavirin (PEG-IFN/RBV), as the therapy causes neuro-psychiatric side effects (depression, anxiety, emotional lability, irritability, insomnia) in a large percentage of patients [12
]. While the potential for HCV treatment to cause more severe neuropsychiatric side effects such as new onset psychosis [14
] and suicidal ideation [15
] is much smaller, these risks warrant careful clinical monitoring. The treatment side effects present a barrier for providers and patients to initiate treatment, and once treatment is begun, these symptoms can result in dose reductions and early treatment discontinuation leading to reduced treatment efficacy [9
There is evidence that the mechanism underlying interferon-induced depression is mediated by deficiency of serotonin in the brain [17
] and selective serotonin reuptake inhibitors are therefore a logical treatment choice. Based largely on findings from a study done with malignant melanoma patients treated with interferon alfa-2b [18
], some clinicians prescribe antidepressants prophylactically prior to beginning patients on HCV treatment. However, neither of the two published double-blind, placebo-controlled randomized clinical trials addressing the use of antidepressants prophylactically during HCV treatment in HCV mono-infected patients [19
] found differences in the rates of development of major depression during HCV treatment between treatment groups (placebo and paroxetine).
In contrast, Kraus and colleagues [21
] conducted a randomized, double-blind, placebo-controlled study to investigate the use of citalopram to treat interferon-induced depression in HCV mono-infected patients already on PEG-IFN/RBV. The findings demonstrated a clear advantage of citalopram over placebo to treat depression which developed during treatment and the study was terminated prematurely. All citalopram patients were able to complete interferon therapy as planned. The authors conclude that a prophylaxis strategy is not necessary but recommend close monitoring of patients during HCV treatment and initiation of antidepressant treatment after the onset of clinically significant depressive symptoms. In addition to the lack of data supporting antidepressant prophylaxis, the potential for antidepressants to cause unwanted side effects in addition to those caused by HCV treatment further argues against this strategy in a mono-infected population with compromised liver function.
Psychiatric stabilization of the patient prior to initiating HCV treatment is critical to successful treatment in terms of reducing adverse neuro-psychiatric events and early treatment discontinuation [22
]. Hepatitis C treatment is therefore ideally conducted in an integrated care setting in which medical, psychiatric, and substance use care is available during the pre-treatment evaluation as well as during HCV treatment [24
]. With the appropriate level of integrated care, the treatment of Hepatitis C can be well managed in populations with very challenging comorbid psychiatric conditions [26
], such as those with bipolar disorder [27
], schizophrenia [28
], and active intravenous drug users [29
In contrast to the literature on therapy of HCV mono-infected patients, there are no completed randomized, controlled trials in co-infected HCV/HIV patients to address whether the use of prophylactic treatment with antidepressants prevents the development of depressive side effects during HCV treatment; while one such study of citalopram is currently underway in Canada, its results are not yet available [31
]. The high prevalence of psychiatric and substance use disorders in the medically eligible HIV-co-infected population leaves open the question of how best to manage these patients when initiating PEG-IFN/RBV, and currently no standard of clinical practice exists.
Individuals with HIV infection are more susceptible to drug-drug interactions and may be more sensitive to the side effects of medication than those without HIV infection [32
]. In addition, studies demonstrate that the effect of HIV on the brain is independent from that of HCV and results in a negative impact on neuro-cognitive functioning beyond that of HCV alone [33
]. For these reasons, the psychiatric management of HCV therapy in HIV-co-infected persons may require a different strategy than in HCV mono-infected persons and warrants dedicated study.
Despite the potential for psychiatric side-effects of PEG-IFN/RBV therapy to contribute to treatment failure, a standardized approach to managing them has yet to be universally adopted in practice. Studies have consistently established that patients who have higher levels of depression at the time of starting treatment with interferon-alfa are more likely than others to develop significant depression during treatment, but the vast majority of studies have not found a relationship between a history of depression in the absence of current depression and development of depressive symtpoms during HCV treatment [37
In the absence of established guidelines for the management of psychiatric status of HIV/HCV-co-infected patients initiating PEG-IFN/RBV therapy, the current study sought to determine what the state of practice is for providers actively engaged in the care of these patients. Herein, the results are reported of a provider survey designed to determine whether consensus exists in the management of these patients, and what factors might impact differing treatment approaches taken by health care providers.