HIV & Hepatitis C: Coping with Coinfection (Part 1)

HIV & Hepatitis C: Coping with Coinfection (Part 1)


Bova, Ogawa, and Sullivan-Bolyai (2010) report that "an estimated 25% to 40% of HIV-infected patients are also infected with HCV [hepatitis C virus], and in some practices the prevalence is as high as 75% to 90%. . . . Recent estimates suggest that approximately 250,000 persons are coinfected with HIV and HCV in the United States" (p. 63), "and with HIV antiretroviral therapy (ART) extending the life of people living with HIV, end-stage liver disease is now a leading cause of death in this population. . . . Studies show that a majority of coinfected patients have at least moderate liver inflammation or other signs of disease progression, . . . however, several studies published over the past 5 years have shown that less than one third of HIV coinfected patients in the United States are deemed eligible for HCV treatment, and under 10% actually receive treatment" (Wagner et al., 2009, p. 715).

Increasing attention has been directed to individuals coinfected with HIV and HCV because

in patients infected only with HCV, the time between infection and development of fibrosis [scar tissue resulting from inflammation of the liver] averages 20 years, whereas in patients coinfected with HIV/HCV, liver disease may develop in 5 to 10 years. . . . [Additionally,] HCV infection . . . influences the course and management of HIV disease, particularly by increasing the risk of ART-induced hepatotoxicity [liver damage]. . . . The goal of HCV treatment is to achieve a sustained virologic response (SVR), which is defined as the absence of serum hepatitis C RNA for 24 weeks after treatment completion. . . . Without HCV treatment, increasing numbers of HIV-infected patients will die either from end-stage liver disease or from HIV-related complications resulting from the inability to use antiretroviral agents because of their hepatotoxicity. (Bova et al., 2010, p. 64)

This is the first of a two-part series. Part 1 provides a medical, psychiatric, psychosocial, and neuropsychological overview of HIV/HCV coinfection, the process of determining eligibility for HCV treatment, and the important role mental health clinicians play in assessing eligibility and intervening with clients who elect to receive treatment for HCV.

Part 2 (to be presented in the Summer 2010 issue of mental health AIDS) will expand on how providers make the decision to offer HCV treatment to individuals living with HIV and chronic HCV infection, how coinfected individuals make decisions to accept or defer treatment for HCV, and the latest thinking on HCV-treatment interventions.

The Chance of a Cure

"A patient's willingness to undergo HCV treatment is likely influenced by how the patient views the efficacy and burden or risk of treatment" (Osilla et al., 2009, p. 993).

On the question of efficacy, it's important to know that "at least six distinct genotypes (numbered 1-6) and more than 30 subtypes of HCV are known," but "the most common genotype present in the United States, genotype 1, is also the most resistant to treatment" (Bova et al., 2010, pp. 63-64). According to Osilla et al. (2009), "standard HCV treatment, which consists of 48 weeks of weekly pegylated interferon (PEG-IFN) injections in combination with daily ribavirin (RBV), . . . has demonstrated a success rate of 30%-45% among HIV coinfected patients across all genotypes, . . . but only 17%-29% among HIV patients with . . . HCV . . . genotype 1" (p. 993). Although "new treatment agents (e.g., protease and polymerase inhibitors) that may improve treatment efficacy are at various stages of development and testing, . . . [they] are not expected to be available for routine practice for at least a few years and [IFN] will remain a component of treatment" (Wagner et al., 2009, p. 715).

As for the risks involved, treatment for HCV has been characterized as "lengthy, rigorous, and associated with side effects that are difficult to manage" (Silberbogen, Ulloa, Janke, & Mori, 2009, p. 114). "Flu-like symptoms (nausea, diarrhea, weight loss)" and "fatigue associated with hematologic abnormalities (anemia, neutropenia) . . . [are] highly prevalent" (Wagner et al., 2009, pp. 715-716). "In addition to physiological side effects, there are also significant neuropsychiatric side effects, including depression, anxiety, irritability, psychosis, suicidality, apathy/malaise, fatigue, impaired concentration, anhedonia, and recurrence of posttraumatic stress disorder symptoms" (Silberbogen et al., 2009, p. 114).

"Not surprisingly, a general fear and apprehension regarding side effects and their impact on quality of life and functioning are common among patients considering treatment" (Osilla et al., 2009, p. 993), and Wagner and colleagues report "dropout rates as high as 40%-50% in community samples of coinfected patients" (p. 716). Yet, "despite these side effects and related patient concerns," proponents of HCV treatment "recommend early treatment for coinfected patients to prevent more serious disease development" (Osilla et al., 2009, pp. 993-994) and "can argue that PEG-IFN/RBV, unlike ART, has a limited duration and at least a chance of a cure" (Wagner et al., 2009, p. 716; see also neuropsychology sidebar).

The Offer of Treatment

"Upon detection of HCV infection, for treatment to be provided, providers must first consider a patient an appropriate treatment candidate, and multiple medical and psychosocial factors can contribute to a provider's reluctance to recommend or offer treatment to a patient" (Osilla et al., 2009, p. 993). In a Seattle HIV-specialty clinic, for example, among 248 predominantly white and male, HCV/HIV-coinfected patients, fewer than half . . . were evaluated for possible [IFN]-based HCV treatment. Only 16% received treatment, and only 2.4% of the entire cohort achieved an SVR. The median time to evaluation for treatment was almost 3 years, a significant period of delay in patients who may have a much more rapid progression to cirrhosis [the final stage of fibrosis], compared to patients without HIV. . . . Similarly, the median time elapsing between evaluation and treatment initiation was 1.4 years. Substance abuse and advanced HIV infection were the primary reasons for nonevaluation. (Scott et al., 2009, p. 928)

According to Wagner and colleagues (2009), substance abuse and mental illness each account for 20%-30% of coinfected patients being deemed ineligible for treatment, as clinicians are concerned that the side effects of HCV treatment may lead to psychiatric deterioration, relapse into substance abuse, poor adherence, and treatment discontinuation. . . . Psychiatric and substance abuse patients have been excluded from most clinical trials, but the little data available show mixed results; some studies find that such patients do equally as well in terms of ability to complete and respond to treatment, . . . while others suggest that patients with active substance abuse and psychiatric problems are less likely to respond and more likely to drop out of treatment. (p. 716)

For this reason, mental health clinicians are often called upon to conduct a psychological evaluation to determine appropriateness for this course of treatment. . . . A pre-treatment psychological evaluation should assess for those factors that will maximize the likelihood of a successful treatment course. Therefore, clinicians should assess for: psychiatric stability and safety (e.g., suicidal ideation, uncontrolled depression), current and past substance use and abuse, knowledge and expectations about treatment for HCV, motivation and ability to adhere to treatment, and psychosocial support.1 . . . After an assessment, clinicians can help prepare patients for treatment by providing education, establishing realistic expectations of treatment success, developing stress-management skills, and identifying areas of concern that patients and/or providers can monitor throughout the course of treatment. Also, a clinician can discuss the potential benefits of a referral for psychiatry consultation to consider psychotropic medication. However, it is important to note that there have been few large-sample, controlled studies evaluating the benefits of prophylactic psychotropic medications in HCV patients on IFN treatment, and that studies with small sample sizes have found inconsistent results. (Silberbogen et al., 2009, p. 117; see alsopsychiatry sidebar)

The Role of the Mental Health Clinician

Silberbogen and colleagues (2009) "have identified areas in which clinicians can intervene [with patients diagnosed with HCV]; these include adjustment to having a chronic medical illness, coping with stigma and relationship changes, management of side effects, and implementing healthy lifestyle changes" (p. 114). Some of the recommendations from these authors in each of these areas follow:

Adjustment to having a chronic medical illness - At the time of diagnosis with HCV, "a mental health clinician can help a patient to process this new diagnosis, generate effective coping strategies, facilitate communication between the patient and hepatologists, and serve as a resource for patients' questions and concerns while providing stability and support" (p. 115). In fact, a key role for the mental health clinician is to ensure that HCV-positive patients have a thorough understanding of their diagnosis and to help translate this knowledge into behavioral change. A well-informed clinician can assess patients' current level of understanding, correct inaccurate beliefs, increase their base of knowledge, and help patients set behaviorally-based goals consistent with treatment recommendations.

Although education may be sufficient to assist some during this adjustment process, other patients may benefit from counseling that helps them to make sense of this diagnosis. Cognitive-behavioral stress-management interventions have proven effective in reducing depressive symptoms and enhancing benefit-finding, positive reframing, and perceived social support in chronic medical populations, including those with HIV. . . . Stress- and anger-management interventions are likely to benefit patients struggling with the unpredictability that often accompanies the diagnosis of a chronic illness. Mental health clinicians can also help patients to identify areas of their life in which they can exert some control (i.e., response to stressors) that may counterbalance these negative psychological sequelae. (pp. 115-116) Coping with stigma and relationship changes - Clinician can help individuals living with HCV to "identity ways to buffer themselves from the impact of stigmatization, such as building a supportive network of friends, family, and medical providers, advocating assertively for . . . [their] needs, and learning how to disclose information while being self-protective. Therapy can also focus on enhancing patients' self-esteem by identifying and building on their positive attributes. Some patients may find value in activities that give them a sense of purpose (e.g., public-awareness programs, political advocacy)" (p. 116). In addition, "mental health clinicians can assist individuals with HCV to navigate . . . changes within their social support network. Communication and problem-solving skills training specifically focused on managing role-changes may prove beneficial, as well as acceptance-based work. Also, participation in couples or family therapy can allow patients to practice these skills in a supportive environment" (p. 116).

Finally, clinicians can help patients build their social support networks by treating mood disorders that interfere with social efforts and by setting small goals toward increased socialization. Clinicians can also assist HCV patients to identify and enhance existing relationships that they may initially overlook or discount. Patients may find it beneficial to engage in "safer" outlets for social interaction, such as online support communities, volunteer positions, or psycho-educational/support groups for patients with HCV, liver disease, or chronic medical conditions. Support groups can be a useful source of information and connection for patients with chronic illness. Mental health providers can make an important contribution to the care of patients with HCV by organizing and/or facilitating support groups focused on issues relevant to this patient population. In addition to providing much-needed social support, these groups can provide education, promote positive health behaviors, and moderate experiences of stigma or discrimination. (p. 117)2

Management of side effects - Once treatment has been initiated, mental health clinicians can use brief standardized measures (e.g., the Beck Depression Inventory) . . . to monitor the presence and severity of psychiatric symptoms . . . and can address specific symptoms in the context of therapy. Stress-management (e.g., relaxation exercises, problem-solving practice), behavioral activation, cognitive restructuring, and enhancement of self-care behaviors (e.g., exercise, proper diet, sleep hygiene) are useful strategies for minimizing potential side effects. Clinicians are also in an excellent position to provide feedback to medical staff, such as psychiatrists, should greater intervention be necessary (i.e., psychotropic medications). (pp. 117-118) In the area of medication adherence, "clinicians can help patients to identify and problem-solve barriers to treatment-adherence, assist in the organization and scheduling of medications, manage side effects, and facilitate access to medical providers" (p. 118).

Implementing healthy lifestyle changes - Because alcohol has a detrimental effect on liver functioning, "reduction in alcohol use is one of the most important behavioral changes patients can make to slow the rate of HCV progression" (p. 118), and "patients with an understanding of the relationship between HCV and alcohol use may be increasingly motivated to make and sustain healthy lifestyle changes" (p. 119). In support of this effort, mental health clinicians can work with patients to develop a concrete change plan based on their stated goals for treatment and anticipate challenges that may interfere with the execution of these goals. Also, patients on IFN treatment who have a history of alcohol abuse or dependence may benefit from ongoing monitoring and support from a clinician with experience in substance-abuse counseling, because the side effects of treatment may result in increased urges and cravings. . . .

Several standardized instruments, such as the Alcohol Use Disorders Identification Test (AUDIT) . . . or the Alcohol Abstinence Self-Efficacy Scale, . . . may prove useful to the clinician assessing and monitoring alcohol intake for patients with HCV. These brief measures are easy to administer and can be used to identify patients in need of additional intervention. All patients should be educated regarding the effects of alcohol on the course of HCV, and, when appropriate, should be evaluated by a chemical-dependency specialist. (p. 118)

Because cigarette-smoking can affect "liver health, treatment efficacy, and quality of life," clinicians are encouraged to review "evidence-based recommendations from research in general populations that can be used as guides for . . . assisting . . . HCV-positive patient[s] to quit smoking or reduce the amount that they smoke. . . . Goals of these recommendations are to increase screening, enhance motivation, and assist patients to reduce tobacco use through problem-solving techniques" (p. 119).

Since "it is likely that improved nutritional status will have a positive effect on disease-progression and long-term outcome for HCV-positive patients," mental health clinicians can take several steps to assist the HCV-positive patient to achieve his or her individual dietary goals. First, clinicians should encourage all HCV-positive patients to pursue a healthy diet and educate patients about how diet can affect their disease progression and quality of life. Unhealthy diet patterns should be identified (e.g., high-sugar and high-fat diets, high daily caloric intake, frequent fast-food consumption, limited fruit and vegetable intake) and addressed. Finally, referrals to nutrition services may be appropriate for some patients, particularly for cases in which the nutritional needs may require a unique or intensive intervention, such as with HCV-positive patients who are overweight/obese, those for whom there are concerns about iron overload, and those who have comorbid metabolic concerns, such as diabetes. (p. 119)

Additionally, with medical-provider approval, HCV-positive patients should be encouraged to participate in regular physical activity to address weight-management, quality of life, and symptom-management. Clinicians can assist HCV patients with setting exercise goals, enhancing motivation to exercise, addressing barriers to activities, and challenging any unhelpful thoughts that interfere with exercise. Devices such as pedometers may motivate patients who are ready to make changes in activity levels. When appropriate, a referral to rehabilitation or physical therapy services for exercise recommendations can be extremely useful. (p. 119) ----Compiled by Abraham Feingold, Psy.D.

References

Bova, C., Ogawa, L.F., & Sullivan-Bolyai, S. (2010). Hepatitis C treatment experiences and decision making among patients living with HIV infection. Journal of the Association of Nurses in AIDS Care, 21(1), 63-74.

Osilla, K.C., Ryan, G., Bhatti, L., Goetz, M., Witt, M., & Wagner, G. (2009). Factors that influence an HIV coinfected patient's decision to start hepatitis C treatment. AIDS Patient Care & STDs, 23(12), 993-999.

Scott, J.D., Wald, A., Kitahata, M., Krantz, E., Drolette, L., Corey, L., & Wang, C.C. (2009). Hepatitis C virus is infrequently evaluated and treated in an urban HIV clinic population. AIDS Patient Care & STDs, 23(11), 925-929. Silberbogen, A.K., Mori, D.L., & Sogg, S. (2005). The Structured Interview for the Treatment of the Hepatitis C Virus (SIT-HCV). Journal of Clinical Psychology in Medical Settings, 12(1), 57-69.

Silberbogen, A.K., Ulloa, E.W., Janke, E.A., & Mori, D.L. (2009). Psychosocial issues and mental health treatment recommendations for patients with hepatitis C. Psychosomatics 50(2), 114-122.

Wagner, G., Ryan, G., Osilla, K.C., Bhatti, L., Goetz, M., & Witt, M. (2009). Treat early or wait and monitor? A qualitative analysis of provider hepatitis C virus treatment decision-making in the context of HIV coinfection. AIDS Patient Care & STDs, 23(9), 715-725. -------------------- 1 One version of the pre-treatment psychological evaluation, "the Structured Interview for the Treatment of the Hepatitis C Virus (SIT-HCV), developed by the Medical Psychology Service at the VA Boston Healthcare System in collaboration with the VA Liver Clinic[,] . . . expands upon a standard psychiatric interview by addressing those psychological and behavioral factors that are unique to this population and essential to consider prior to recommending a patient for IFN therapy. . . . On the basis of the information gathered during the administration of the SIT-HCV, clinicians can make behavioral recommendations that will enhance a patient's likelihood of attaining an optimal treatment outcome while minimizing the impact of incapacitating side effects" (Silberbogen, Mori, & Sogg, 2005, p. 58). The complete protocol can be found in the appendix of Silberbogen and colleagues' article.

2 "As the nation's largest care-provider of patients with HCV, the [Department of Veterans Affairs] has developed a comprehensive website designed to meet both patients' and providers' needs (www.hepatitis.va.gov). . . . Available resources for mental health providers include a 'how-to' program guide that outlines the basic steps for initiating and maintaining a hepatitis C support group. This valuable resource includes a discussion of issues to consider when developing a group, suggestions for group topics, descriptions of therapeutic and facilitation techniques, and sample forms and handouts" (Silberbogen, Ulloa, Janke, & Mori, 2009, p. 117).

Neuropsychology of HIV/HCV Coinfection

"HCV mono-infection is associated with significant impairment in neuropsychological domains typically characterized as 'subcortical' in nature, with predominant impact on attention, information processing speed, and verbal memory. Further, evidence of neuropsychological impairment among HCV mono-infected individuals exists independent of comorbid substance abuse and severe liver disease, raising the possibility of direct brain involvement from HCV" (Martin-Thormeyer & Paul, 2009, p. 223). Moreover, individuals infected with both HCV and HIV express more severe neuropsychological impairment than individuals with HIV alone but the mechanisms underlying these effects remain unclear. To date a handful of studies have examined neuropsychological function among individuals co-infected with HCV and HIV. Among these studies there is notable variability in the methods to examine neuropsychological function, the use of various comparison groups (e.g., HCV alone, HIV alone, both mono-infected groups compared to co-infected patients), and the focus on various laboratory indices of disease burden. These methodological differences require some caution when drawing conclusions regarding the impact of co-infection on cognitive outcome. For example, a number of studies did not involve a comprehensive neuropsychological assessment, and therefore, conclusions regarding the neuropsychological pattern associated with co-infection remains premature. With that caveat noted, there is some suggestion in the literature that several domains of cognitive function are more likely impacted by co-infection than others.

Decreased processing speed and psychomotor speed among co-infected individuals is a commonly reported outcome of the studies . . . [although e]vidence of selective impairment in psychomotor speed/information processing is not universal. . . . [In fact, n]ot all studies have reported greater cognitive impairment among co-infected patients. . . . When taken collectively the majority of studies have reported more severe neuropsychological impairment among co-infected patients than mono-infected patients. (Martin-Thormeyer & Paul, 2009, pp. 224-225) Importantly, "recent studies of dually infected subjects indicate that neurocognitive function may improve with successful therapy for either disorder" (Gonzalez, Quartana, & Martin, 2009, p. 223).

References

Gonzalez, R., Quartana, P.J., & Martin, E.M. (2009). Co-occurrence of HIV, hepatitis C, and substance use disorders: Effects on brain functioning. In R.H. Paul, N.C. Sacktor, V. Valcour, & K.T. Tashima (Eds.), HIV and the brain: New challenges in the modern era (pp. 213-233). Totowa, NJ: Humana Press. Martin-Thormeyer, E.M., & Paul, R.H. (2009). Drug abuse and hepatitis C infection as comorbid features of HIV associated neurocognitive disorder: Neurocognitive and neuroimaging features [Review]. Neuropsychology Review, 19(2), 215-231.

Psychiatry & HIV/HCV Coinfection

According to Silberbogen and colleagues (2009), "numerous studies . . . document high prevalence rates of preexisting psychiatric disorders among patients with HCV. . . . Within the HCV-positive population, approximately 27%-78% of patients are diagnosed with past or current substance abuse, 15%-62% with mood disorders, and 30%-40% with anxiety disorders such as PTSD [posttraumatic stress disorder]" (p. 115).

With regard to the population of co-infected individuals, however, and "in the absence of established guidelines for the management of [the] psychiatric status of HIV/HCV-coinfected patients initiating PEG-IFN/RBV therapy," Weiss and Morgello (2009) "sought to determine what the state of practice is for providers actively engaged in the care of these patients" (p. 532). The investigators developed and reported on "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" (p. 532). They focused in particular on "the use of prophylactic treatment with antidepressants [to] prevent . . . the development of depressive side effects during HCV treatment" (p. 532).

From a pool of 236 "expert" providers invited to participate, the sample consisted of 92 providers who completed the anonymous online survey, 26% of whom were psychiatrists. With regard to practice setting and provider discipline, Weiss and Morgello found that "the psychiatric management of HIV-coinfected patients being treated for HCV occurs in multiple contexts (varying from comprehensive integrated clinics to individual practices) and is done by providers from a wide range of disciplines (infectious disease, psychiatry, internal medicine, nurse practitioner). The survey was able to establish the practice patterns of expert providers who are predominantly physicians working in varied practice settings internationally" (p. 535).1 Notably, most of the nonpsychiatrist survey respondents have "very limited access to psychiatric consultation" (p. 535).

With regard to these practice patterns, more than one third of providers indicate[d] that they use or offer the option of antidepressant use prophylactically in HIV-positive patients with no past or current depression beginning HCV treatment, and more than three quarters do so in patients with a history of depression but no current symptoms of depression. The most experienced nonpsychiatrist providers were more likely to use antidepressants prior to the start of treatment in HIV-coinfected patients as compared to in HCV mono[-]infected patients. There . . . [wa]s consensus among providers to leave psychiatric medication unchanged in patients currently treated for unipolar depression. (p. 531)

Weiss and Morgello conclude that "many expert providers prescribe antidepressants to HIV/HCV-coinfected patients initiating [HCV] treatment in the absence of symptoms of depression, despite the lack of data supporting this approach in this population" (p. 531). The investigators surmise that "this pattern of prescribing . . . may be related to . . . limited access to psychiatric consultation, with providers viewing the prophylactic use of antidepressants as the safest and most cautious treatment approach" (p. 536). Weiss and Morgello advocate for "increasing [nonpsychiatrist] provider skills and competence through advanced training in psychiatric assessment and management[, because this] would likely reduce the extent to which these providers use antidepressants prophylactically and could potentially lead to better HCV treatment outcomes" (p. 536). Additionally (and importantly), "research is needed to provide an evidence base to guide the optimal psychiatric management of HIV/HCV-coinfected patients beginning [HCV] treatment" (p. 531).

References

Silberbogen, A.K., Ulloa, E.W., Janke, E.A., & Mori, D.L. (2009). Psychosocial issues and mental health treatment recommendations for patients with hepatitis C. Psychosomatics 50(2), 114-122.

Wagner, G., Ryan, G., Osilla, K.C., Bhatti, L., Goetz, M., & Witt, M. (2009). Treat early or wait and monitor? A qualitative analysis of provider hepatitis C virus treatment decision-making in the context of HIV coinfection. AIDS Patient Care & STDs, 23(9), 715-725.

Weiss, J.J., & Morgello, S. (2009). Psychiatric management of HIV/HCV-coinfected patients beginning treatment for hepatitis C virus infection: Survey of provider practices. General Hospital Psychiatry, 31(6), 531-537.

1 Wagner et al. (2009) point out that "unlike HCV mono-infected patients, who are typically treated by liver specialists (e.g., hepatologist or gastroenterologist) with extensive experience with HCV treatment, HIV coinfected patients are most often treated by HIV primary care providers (with relatively limited experience with PEG-IFN/RBV) because liver specialists are unavailable" (p. 716).