Adherence, Psychiatric Disorders and HIV

[Guest guest]

Adherence, Psychiatric Disorders and HIV CME/CE

Glenn J. Treisman, MD, PhD; Reviewers: Angelino, MD; Bartlett, MD

Complete author affiliations and disclosures are at the end of this activity.

Copyright © 2007 Medical Education Collaborative.

Contents of This CME/CE Activity

Adherence, Psychiatric Disorders, and HIVGlenn Jordan Treisman, MD, PhDAvailable As: Slides/Audio | Slides/Transcript | Audio

Adherence, Psychiatric Disorders, and HIV

Introduction

I am Glenn Jordan Treisman, MD, PhD, associate professor of both medicine and psychiatry at s Hopkins University School of Medicine. I have a presentation on Adherence, Psychiatric Disorders, and HIV that I thought you might find interesting and would like to share it with you.

Learning Objectives

Slide 1. Learning Objectives

The learning objectives for this presentation include a discussion of the barriers to adherence and compliance, describing methods to improve adherence, and recognition of psychiatric disorders in HIV-infected patients.

Adherence Issues in Challenging Populations

I am going to divide this into a couple of parts. The first part will discuss adherence issues in challenging populations. I believe that HIV has become a psychiatric epidemic and that it is an epidemic of people who are vulnerable. These are adherence issues in vulnerable or challenging populations of patients.

Slide 2. Goals of therapy

There are a number of goals for HIV therapy, which are debated and discussed. One of them is a reduction in HIV-related morbidity and mortality, which is closely associated with the second goal, which is suppression of viremia. The third goal is restoration and preservation of immune function. However, there are several other incredibly important issues that are less often discussed.

One of the goals of good HIV therapy is to decrease the emergence of resistance. Patients who are poorly adherent to their regimens undergo a tremendous increased risk of developing resistant virus. There are a number of things that we can do to minimize that risk and to reduce the development of resistant virus.

Another goal is the minimization of toxicity and disruption of lifestyle. Many of the medications we use require special meals, special circumstances, and frequent dosing. We try to minimize the intrusion into somebody’s life by minimizing the side effects of their medications. Additionally, some of the toxicities of HIV medication can profoundly affect other people’s general health. So patients with HIV infection should at least consider the impacts on other systems of their body that HIV drugs can cause besides the immune system. Finally, there is a potential for the reduction of transmission in effectively treated HIV patients. At several recent meetings, this topic has been increasingly debated. Is it reasonable to expose patients to HIV medications earlier in the course of their treatment so as to minimize the possibility of transmission? While this issue is still being debated, it is debated in an environment where we really do not know the potential benefit of early treatment. We have come to believe that it is not necessary to treat HIV until T cells fall below 400, and probably between 200 and 350. But many people believe that early treatment is advantageous. However, the data are not really conclusive about how early patients should be treated.

Slide 3. HIV therapy is associated with suboptimal adherence rates

I want to discuss HIV therapy and adherence. I have a slide showing HIV therapy associated with suboptimal adherence rates. There are many different studies like this one showing that, in general, patients really have difficulty taking their medications every day. Meanwhile, the research shows that if patients take 95% of their medications, they gain the maximum therapeutic benefit in terms of sustained viral response. In the real world, patients rarely achieve 95% adherence of all doses.

Slide 4. Optimal therapeutic response and adherence to protease inhibitor therapy

The next slide, Optimal Therapeutic Response and Adherence to Protease Inhibitor Therapy, demonstrates that as adherence falls off, the therapeutic response falls off fairly quickly. This particular slide is based on MEMS® cap data. MEMS caps are small recording devices that can be put on a pill bottle that indicate when the bottle was opened. They are considered by many people to be the gold standard for adherence studies. But even in MEMS caps studies there is some question about whether the patient opened the bottle and took the medicine or whether the patient just opened the bottle.

Slide 5. Adherence is critical to success of HIV/AIDS treatment.

There are a lot of studies showing that adherence is critical to the success of HIV/AIDS treatment. In this slide, we see that suboptimal adherence to antiretroviral therapy leads to incomplete viral suppression and the emergence of resistant virus. There is also a clear increase in mortality associated with patients who have suboptimal adherence. When you start working in diverse and vulnerable populations, there are a lot of different strategies that need to be considered for improving HIV adherence.

Slide 6. Obstacles to adherence to HIV therapy

Some of the obstacles to HIV adherence include cost of medication, inconvenient appointments, and transportation problems, as well as a variety of patient-related factors that I will discuss later. A number of healthcare professional factors include difficulty finding extremely experienced HIV providers and difficulty dealing with barriers between patient cultures and physician cultures. Finally, there have been a number of regimen characteristics that I am going to cover that have been shown to change the way patients take their medication.

Slide 7. Toxicity a major reason for ART regimen discontinuation: ICONA study group

One of the major reasons that patients discontinue medication is toxicity. In this slide, I have a circle graph showing that toxicity is the reason for treatment discontinuation in 58% of the cases in one study. Therefore one can see that toxicity plays a major role. Different medication regimens have quite different toxicities. While there is no gold standard for monitoring HIV therapy adherence, there are methods that are easy and there are methods that are harder.

Slide 8. Detection and monitoring of HIV therapy adherence

On this slide I have summarized some of those methods. Use of the MEMS cap is considered by some people to be the best method. However, other people believe that monitoring prescription refill and pill counts is even better because a patient would have to take the medication out of the pill bottle and actually throw it away rather than just opening and closing the bottle.

Monitoring drug levels is clearly the most accurate way of determining whether or not patients are taking their medication. However, the burden of having somebody come in and checking their medication blood level several times a week is extraordinary. Self reports, questionnaires, and visual analog scales have been used and probably do reflect adherence behaviors fairly reasonably in most populations.

There are a variety of studies that have looked at how patients believe they will take their medications. In addition, a variety of studies show how providers believe their patients will take medications.

Slide 9. Providers believe these patients will have poor adherence

In one study, providers were asked whether or not they believed their patients would adhere well to treatment. On the right side of this slide, providers listed the percentage of their patients who they thought were likely to be poor adherers. Obviously, active alcohol abusers, active injection drug users, homeless people, depressed people, people with a history of drug injection, women with children, less educated people, minority, and low-income patients are likely to be poor adherence patients. However, data are only associated with a small number of those impressions.

Slide 10. Interventions that may enhance adherence

The next slide provides an overview of interventions that have been shown to improve adherence. Education probably is the best bang for the buck. A number of studies support the idea that education provides the best bang for the buck. In other words, adherence to therapy improves more with education than with almost any other parameter you can measure. The problem is that most of the patients are fairly well educated and we have mined both the education and peer education methods fairly extensively. Improving attitudes about medication and improving the patient’s sense of self-efficacy has clearly been associated with better adherence.

Acquisition of behavioral skills and coping skills, improved social supports, external cues like pagers, medication charts, and pillboxes are all very helpful. We often try to get family members involved in reminding patients to take their medication, although we will also use pagers for that.

Improved communication between the physician and the patient, continuous reinforcement over time, giving people tokens, coupons, vouchers, or direct payment for particular behaviors, and continuous reinforcement by the clinician saying they are doing a great job can be very helpful to patients. Other helpful techniques include telling patients their viral loads and T cell counts. It is important to encourage patients, reminding them that what they are doing is difficult, especially late in treatment, to continue adherence at very high levels, but that it is important.

Slide 11. Interventions that may enhance adherence: Medication regimens

In the next slide, some medication regimen issues are listed that have been shown to help adherence. The first one is to simplify medication regimens as much as possible. It is important to avoid complicated, high-pill-count regimens; avoid regimens that restrict lifestyle and have difficult dietary restrictions; and avoid medications that are not really necessary.

Integrating HIV medication into patients’ lifestyle is very important. You can link the medication regimen with established daily routines. It might be helpful to ask patients if morning or night is a better time for them to take their medications. Many patients will tell you that the morning is difficult for them, they have difficulty getting up, and they get up at unpredictable times; where the evening is the best time of day for them to take medications. While other patients say the best time for them is when they brush their teeth in the morning because they always do that as part of their routine. So trying to link the medication to a particular thing that happens every day is very useful.

Directly observed therapy has clearly been shown to enhance medication adherence, as have peer educators and peer coaches. Managing side effects and particularly anticipating and monitoring patients for side effects are extremely useful.

Another technique that is used involves doing dry runs with dummy medication before initiating complex antiretroviral therapy. There is some research in this area. It is not something that I have found particularly useful in my own work, but I know a number of people do it and think it is very helpful for patients.

Slide 12. Toward simpler regimens: Coformulations and once-daily pills

One of the goals in HIV therapy is to try to develop simpler regimens. Among the things that have been developed are coformulations of medications and once-daily regimens. This slide lists a number of coformulations of medication that are out in single pills and also once-daily options for medication treatment. These are medications that can be taken as a single daily dose rather than several times a day. Some of these dosages can not be used for patients who are treatment-experienced or who have developed viral resistance. But for the most part, treatment naïve patients can often benefit from a once-a-day dosing regimen.

Slide 13. Adherence issues in challenging populations

There are a number of populations of patients for whom adherence issues have been particularly challenging. Homeless patients have transportation issues and all kinds of barriers to effective adherence. Substance users lead chaotic lives, are often intermittently intoxicated while they are trying to sober up, which can lead to poor adherence. There are a variety of psychiatric disorders that will be discussed later that can make it difficult to treat patients. Adolescents and young adults have chaotic lives and have a tendency to be only intermittently compliant with their medications. Women, particularly single parents who have families, children that they are responsible for, as well as a variety of very difficult situations in their lives can be very challenging in terms of developing good adherence behaviors.

Substance Use and Adherence to Antiretroviral Therapy

In this next section, I’d like to talk about substance use and adherence to antiretroviral therapy (ART). Although most of us, and I am included in this group, believe that substance use disorders profoundly negatively influence adherence, there have been a number of studies in substance abusing populations that have found that not to be the case. There are also studies that have shown that that is the case. So there is some debate about how much adherence problems are associated with substance use disorders. I am going to review a little of the data in this section.

Slide 14. Drug Use and HIV are inextricably linked.

However, I will say that drug use and HIV are inextricably linked. This slide shows you that 25% of new infections, which is 10,000 people a year plus or minus, are directly attributable to injection drug use, and that in some urban settings, the proportion is quite a bit higher. Substance use disorders are extremely prevalent in patients with HIV. An estimated 360,000 people with HIV in the US are active substance users. So these issues are very important.

Slide 15. Daunting issues for substance users

One of the immediate problems that face substance users when they come for HIV treatment is that their addiction issues often outweigh their long-term health issues. They are almost always impoverished and have difficulty with housing. They have poor social support networks and have used up a lot of their resources in terms of their families. There are lots of medical complications related to their substance use that can interfere with their HIV treatment. Hepatitis C is a covariant in patients with intravenous drug use such that three quarters of patients with intravenous drug use probably have both hepatitis C and HIV together.

There are a number of psychiatric conditions that are daunting issues for substance users. Between 50% and 80% of patients have an active psychiatric disorder other than substance use. There is distrust of the medical establishment and there is a lot of physician resistance to treating intravenous drug users. These things have all been seen as clear barriers to substance abuse patients getting adequate treatment.

Slide 16. Chronic drug users: Poor access to care

Chronic drug users are particularly at risk of having poor access to healthcare. This is true both in the HIV and non-HIV population. It has been shown that chronic drug users are at increased risk for disease overdose and injury. They have higher mortality and they use less healthcare, but are more likely to use healthcare in an emergency room and inpatient care, and not receive outpatient follow up. Overall, they are less likely to have a regular source of healthcare. Antiretroviral therapy, therefore, is less accessible to substance users.

Slide 17. Access to ART by substance users: Lower, but increasing

In this slide I show you that antiretroviral access is related to access to general medical care in patients with HIV and that antiretroviral recipients are more likely to report physician visits, care continuity, and coverage with insurance.

Active substance users are less likely to receive antiretroviral therapy and people who are recovering and not active users are more likely to receive it. By 1999, the HIV Cost and Services Utilization Study noted that the number and proportion of intravenous drug users never on antiretroviral therapy were finally declining. In the Baltimore Cohort Study, the proportion of intravenous drug users on antiretroviral therapy increased dramatically between 1996 and 1999. We know that although physicians are somewhat reluctant to treat intravenous drug users, they are becoming more comfortable with this in HIV settings. However, there are still a number of barriers to access.

Slide 18. Barriers to access

In this slide, I show you that most physicians who treat HIV have little or no training in addiction medicine and little or no training in psychiatry. There is substantial provider resistance. In this slide we have used the term “prejudice,†regarding treatment of patients who are substance users. Many physicians believe that drug users are not likely to take medications and, therefore, it may be pointless to treat them.

Slide 19. Barriers to access (cont’d)

The substance users themselves have a lot of mistrust in the medical system and have often had negative experiences with physicians in the past. They are also distrustful of HIV and HIV care and perceive their care as unlikely to being beneficial. There is also a perception that the doctors who take care of HIV patients who are substance users are inexperienced, insensitive, and indifferent to their issues. In addition, there are also a number of structural barriers. There are limits in terms of provision of care to patients without insurance, waiting times, difficulty with continuity of care. There are also changes in panels, and physicians often turn over rapidly in HIV clinics. There is also a separation between drug treatment and other kinds of care, rather than integrated care.

These things all have a profound impact on the way substance users have to work to get access to psychiatric and substance abuse care while at the same time getting HIV care.

Slide 20. Relationship between adherence and past substance use

There is clearly a relationship between adherence and substance use, but most studies show no association in recovering patients. On this slide I have some literature views and meta-analyses that have shown that patients who are recovering tend to be equally adherent to patients who have never had a substance use disorder, while patients who are currently using are much more likely to have poor adherence.

Slide 21. Relationship between adherence and current substance use

There are several studies that have looked at this issue. In this slide I mention the Baltimore study, which has looked at antiretroviral drug use in patients who are current and past users. These researchers have shown that the past users are equivalent to patients who have never used drugs, whereas current users have poorer adherence.

Slide 22. Relationship between adherence and current substance use (cont’d)

This slide mentions the relationship between adherence and current substance use in that different drugs have different effects on adherence. Cocaine use is particularly associated with low adherence in a number of studies, as is alcohol use. However, there are some studies looking at opiate users that have not been able to show a decreased adherence in these patients.

Slide 23. Correlates of lowered adherence among substance users

In patients who have substance use disorders, there is increased susceptibility to side effects and, thus, more complaints about HIV. Thus, patients who are chronic substance users have a tendency to be less likely to be compliant with their HIV medications because of their complaints about side effects.

There are a number of social and cultural influences and networks that may have both a positive and a negative influence on the way patients perceive HIV care. Substance users have often alienated friends and family, have difficulty with the appropriate social structure in order to get HIV treatment, and often have a void in coping mechanisms and a belief that HIV medications may interfere with their ability to benefit from their street drugs.

Slide 24. Methadone Maintenance Treatment (MMT) and buprenorphine and improved adherence

On the other hand, methadone maintenance, when it is given collaboratively with HIV treatment, has clearly been shown to have a beneficial effect on antiretroviral adherence. Both methadone maintenance and buprenorphine are summarized in this slide. Looking at cohort studies, you can see that comorbid treatment of both substance use disorders and HIV improves adherence and outcome quite significantly. So there are a number of strategies that we can adopt to help us with our patients.

Slide 25. Adherence interventions

I think the most important thing, and something that I have been stressing in my work, is the integration of care strategies. We need to integrate substance use disorders, psychiatric disorders, and HIV and hepatitis C treatment under a single roof so that there is a multidisciplinary team present to treat patients. This includes multimodality treatment, including drug treatment and psychiatric services, as well as employment training and vocational rehabilitation. Healthcare providers who see themselves as sort of the quarterback in the treatment team need to assess adherence, deal with side effects, and tailor the regimen to patients’ lifestyle. They also have to assess the patients’ understanding and refer them to appropriate resources to get the care they need. Thus, mixed and multifactorial approaches have been shown to work best.

Slide 26. Specific adherence interventions for substance users

A number of specific adherence interventions have been helpful for substance users. The one I mentioned most clearly is methadone maintenance and buprenorphine maintenance, including directly observed therapy, which have a very powerful effect on adherence.

Peer support, integrated low-threshold services, medication counseling and pillbox refill, drug treatment at a single center, and positive reinforcement-based queuing, in which patients are directly rewarded for adherence using either vouchers or money, work during reinforcement. However, they have not been shown to have a sustained outcome after reinforcement is stopped.

Slide 27. Drug interactions between methadone and ART

There are a number of concerns among patients regarding methadone and antiretroviral drug interactions. They are often very concerned about the possibility that their methadone effect will be diminished and, therefore, they will experience withdrawal when they start antiretroviral medications. In reality, a number of medications have been shown to reduce the area under the curve for methadone in patients. Specifically, nevirapine, efavirenz, ritonavir, and nelfinavir have been shown to decrease methadone levels in patients. However, it is not clear how much of a clinical impact this has. Abacavir has been shown to increase the clearance in methadone in one study, and methadone may increase the action of AZT and lamivudine. It is important to remember that these are predicted interactions rather than actual clinically measurable interactions.

Methadone has been shown to decrease the absorption of didanosine and stavudine, however, the clinical implications of this are not entirely clear. Because of this, patients may not take their antiretroviral therapy because of worries about the impact on their methadone dose. It is incumbent upon all providers to think about this, to educate patients, and to look carefully at patients who are starting an antiretroviral therapy to make sure that it does not affect their methadone dose. They should be thinking about how methadone treatment can be managed in a patient who has a drug interaction. The last thing I will mention is that efavirenz often gives patients a positive drug test for marijuana. In methadone programs that monitor for marijuana use, this can be a serious problem.

Slide 28. Case study: Background

Case Study

Here is a case study that goes along with the things we are discussing. This patient is a 47-year-old African American male from New York who has been using drugs for 30 years. He is a regular heroin user and has had intermittent detoxifications and methadone maintenance, but has used heroin for most of the time. He is an alcohol and marijuana user as well. He also has had some periods of mixing in crack and cocaine to his regimen.

Slide 29. Diagnosis and early treatment

He tested HIV-positive in 1986 in prison and was prescribed AZT. He spent the next 10 years in and out of HIV care and lived intermittently between his mother’s house and the homes of two women with whom he was involved.

Slide 30. Diagnosis and early treatment (cont’d)

While he was on AZT, he had side effects including nausea and believed that AZT was bad for his health. He knew people who were taking AZT who had died and he took AZT sporadically at the very best. At that time, he was neither confident nor connected with his HIV care. And when he was trying to get clean, he often treated his HIV with a variety of homeopathic remedies including herbs. His attitude toward HIV and drug use was that people are fine until they stop using drugs, and then they get sick and die.

Slide 31. Diagnosis and early treatment (cont’d)

He continued to use heroin and to drink heavily, but stopped using cocaine. He took his medication sporadically depending on whether or not he was “partyingâ€. He believed taking his medications while on heroin might be harmful. And sometimes he went several days without taking medications when using heroin.

Slide 32. Deterioration accelerates

His deterioration accelerated and, in 1999, he moved upstate to be with a woman who was also a drug-using friend. At that time, he was heavily using heroin, cocaine, and alcohol and felt tired and weak much of the time. He hated living upstate and began to have problems in his relationship. He subsequently began to have AIDS wasting and visited an HIV clinic. At that time, his CD4 showed 70 T cells with a viral load of 250,000. He was told he was not a candidate for antiretroviral treatment because of his history of missed appointments, drug use, and adherence problems. He was given some pills to prevent infection, which probably represented opportunistic infection suppression.

Slide 33. Treatment question

At this point you might ask the question what possible interventions could have been implemented to help this patient become a candidate for antiretroviral therapy. The obvious answers that you can think of are peer education, referral to a social worker, and counseling by a clinician on the importance of adherence.

Slide 34. Stabilization

So the patient was moved back to New York City in 2001. He stopped using drugs except for occasional heroin and occasional alcohol and became open about his history with a new physician. At that time, his doctor prescribed the antiretroviral therapy and integrated it into his daily routine. He was also referred to a drug treatment program and a peer program for adherence support. His partner began helping him take his medications and he has had 2 years of continuous HIV care with relatively good viral suppression and nearly 90% adherence. He has become more motivated to stop using drugs and has actually become a peer counselor in the last few months.

I would like to discuss that case for just a moment. Let us think about what kinds of things we now know that we may not have known back then about patients with heroin use disorders and with substance use disorders that might have been beneficial to this patient. I have reviewed a number of those things, but I would like to go on to a section I call Overcoming Challenges in Common Mental Health Issues. I would like you to think about application of this section to the chronic drug-using patient that I just mentioned above.

Overcoming Challenges in Common Mental Health

I believe that psychiatric disorders are partly driving the HIV epidemic. I also believe the HIV epidemic has essentially become a psychiatric epidemic.

Slide 35. HIV is a psychiatric epidemic

In this slide I describe my belief that HIV increases the risk for psychiatric illness and there are good data for that. There are psychiatric illnesses that increase the risk for HIV, and there are also good data for that. Effective treatment of psychiatric illness has been shown to improve patient outcome, and can decrease HIV transmission. I will show you a little of the data regarding that.

Slide 36. Vicious cycle of mental illness and AIDS

In this slide I show you the vicious cycle of mental illness and HIV. On the left side, I show mental illness driving a variety of behaviors that increase the risk for getting infected. On the right side of the slide, I show AIDS driving a number of things that worsen mental illness.

The very things that interfere with a patient’s ability to prevent HIV infection and increase their risk for getting it also interfere with adherence and decrease the patient’s likelihood of benefiting from HIV treatment. So the things that drive getting infected also drive poor adherence and poor outcomes. When we first began describing the high rates of psychiatric disorders in patients with HIV, initially most people thought this was limited to urban inner-city troubled populations.

Slide 37. Psychiatric disorders in new medical intakes for treatment of HIV

This slide shows a summary of the first study that we published regarding the high rates of psychiatric disorders in patients with HIV infection. However, many people have gone on to find exactly identical or almost perfectly identical rates in both urban and rural populations, as well as drug abusing and nondrug abusing populations. Even in gay men who did not use needles in our population, there were very high rates of substance use disorders. We were astonished to find the high rate of cognitive impairment in our population. This 18% of patients who had cognitive impairment represents a group of patients who are unable to benefit from many of the standard interventions for HIV patients because of their cognitive slowing and cognitive difficulty. Therefore, interventions have to be tailored to deal with their cognitive impairment and overcome it in order for them to benefit from treatment.

Slide 38. Psychiatric barriers to adherence

You can describe the various psychiatric barriers to adherence as coming down in a variety of categories. Here, I have divided them out into diseases of the brain including major depression, bipolar disorder, and schizophrenia, problems of personality or temperament, particularly extroversion and instability, problems of addiction and behavior, and problems of experience and assumption.

Slide 39. Vicious cycle of depression and AIDS

I want to just describe each of these in brief to you as ways in which they affect our HIV-infected patients. The next slide is a cartoon of depression in AIDS, which is similar to the cartoon I already showed you. When I talk about depression here, I am talking both about major depression, the disease kind, and demoralization, the sense of hopelessness and misery that patients get associated with psychological stressors. You can see here that those things are made worse by HIV infection, but that depression itself drives the risk for AIDS.

Slide 40. Depression and delay in ART initiation

A number of studies that support this idea, including a study showing patients with a history of depression, have a delay in initiation of antiretroviral therapy. Patients with a history of IV drug use have a delay in initiation of antiretroviral therapy. Patients with opportunistic infection or elevated viral load received earlier antiretroviral therapy in the same treatment population suggesting that patients had to go as far as to develop significant symptomatic problem before they get treated.

Slide 41. More rapid discontinuation of ART in depressed persons

The other thing that I can show you in this slide is that patients with depression are more likely to discontinue antiretroviral therapy and discontinue it more rapidly. This slide divides patients on highly active antiretroviral therapy into those with a greater than 15 Beck depression inventory and those with a lesser than 15 Beck depression inventory. The Beck depression inventory is a common screen for major depression and a way of following patients for the severity of their depression.

Slide 42. Depression impairs HIV medication adherence

What you can see is that the depressed patients had a much more rapid and a much more profound dropout rate than patients who were not depressed. Depression has been shown to impair HIV medication adherence. I will not take you through all these studies, except to show that there are many studies.

Slide 43. Depression decreases AIDS-free survival in patients on ART

Finally, in this slide, you can see from the HERS cohort that there is an increase in HIV-related mortality associated with major depression. It is incredibly important to know that not only is HIV bad for taking antiretrovirals, but it goes on to show that patients who have depression are more likely to die. Depression is an extremely underrecognized and undertreated condition.

Slide 44. Depression is under-recognized and undertreated

This slide shows a study of 475 HIV-infected men, 37% of whom had moderate to severe depression and 40% of these depressed men received mental healthcare. However, only 3.4% of the depressed men received antidepressant medications. Our studies indicate that at least 20% of the men in that population probably had a mood disorder that would have been affected positively by antidepressant medication.

Slide 45. Differential diagnosis of depression

In this slide, I want to talk for a minute about what depression actually is because I believe that there are two kinds of depression. There is the depression that we all have had in our lives and at the bottom of the slide I have the word demoralization. The DSM prefers the term adjustment disorder. That kind of depression everybody has experienced at some point. It is the depression that is associated with adverse psychological experience and essentially follows the stages of grieving that have been described by Kubler-Ross in her book, “On Death and Dying.†Demoralized patients experience an initial sense of disbelief, followed by a period of numbness, followed by a period of hopelessness and extreme despair. That despair continues as long as the stressors are present. In many patients with HIV, those stressors are significant.

Slide 46. Major depression diminishes

At the top of the slide I have a condition that I describe as major depression. This kind of depression I believe to be a disease of the limbic system of the brain, particularly the reward pathways of the brain. It can occur in people who have relatively stress-free lives and attacks people who do not have HIV and, in fact, are doing quite well. However, it is easy to confuse depression and demoralization in the HIV clinic because many patients have both. The key to understanding this is that demoralized patients respond better to supportive care, encouragement, and time; whereas patients with major depression probably need both psychotherapy and antidepressant medication to get the most benefit.

In general, depression is diagnosed in patients by looking for a change in their mood, their vital sense, and their self-attitude. That is they feel sadder, they feel sicker, and they feel bad about themselves.

Unfortunately, HIV is a chronic medical problem that is stigmatizing. It can make people sadder. It certainly makes people feel sicker and it can make them feel bad about themselves. These classic symptoms of major depression have not been as useful in patients in the HIV clinic as they are in high functioning patients who come as an outpatient for a psychiatric evaluation.

Slide 47. Anhedonia

The fourth classic feature of major depression is anhedonia. This is the loss of rewards, pleasure, satiation, or satisfaction associated with particular behaviors, both appetite-directed behaviors like eating, sleeping, and sex, and function-directed behaviors like work, hobbies, or exercise. Patients will tell you it is not as much fun as it usually is or it is not as enjoyable or I can not get what I am supposed to get out of things.

The patient I always describe, who probably taught me this the best, but certainly taught me the first time, was a patient who came to me who is an inveterate bowler. He bowled constantly, three times a week, never missed a league, never missed a game. When he was finally referred to psychiatry, he came to me and said you know, Dr. Treisman, things at work have not been as good as they could be. And things with my wife have not been as good as they could be. But this is now starting to affect my bowling. After a treatment with antidepressants he said to me, “you know, Dr. Treisman, when I was sick and I would get a strike, I would think that is what is supposed to happen, but now that I am better, I have gotten my ‘yeah’ back from bowling. When I get a strike I turn around to my team and I say ‘yeah.’ I think depression is a disease of your yeah receptors.â€

I think that was a very brilliant insight on that patient’s part. Depression is a disease of your yeah receptors. When you are depressed, nothing gives you that sense of yeah or that sense of good feeling like it should in ordinary life.

It is my opinion that anhedonia is the most sensitive and specific indicator of major depression in patients with HIV. It is the thing I tell clinicians to spend the most time looking at when they are trying to decide if depression is the diagnosis.

Treating Patients With Major Depression on ART

Slide 48. Practical aspects of treating major depression in patients on ART

Now there are many practical aspects of treating major depression in patients on antiretroviral therapy. But I would urge every clinician who does HIV care to become good at treating most cases of depression.

The good news is no antidepressant has been shown to be clinically superior to the others. So what you want to do is pick an antidepressant where the side effects of the drug are going to work for you rather than against you. Some drugs cause weight gain, some cause weight loss. Some drugs cause constipation and some drugs cause increased GI motility. Some drugs cause sedation and some drugs cause alertness. Because of that, you want to be able to know something about the side effect profiles of the various classes of antidepressants while picking a drug.

Because of potential drug/drug interactions that can happen, drugs with a large therapeutic index like the newer antidepressants and particularly the SSRI drugs may be easier for most clinicians to use. However, drugs with a narrow therapeutic index, like tricyclic antidepressants and lithium, may be used as well. Although they have potential drug/drug interactions, you are monitoring blood levels of them closely in patients with HIV infection or on antiretroviral therapy..

It may be easier to adjust the dose in a patient who is receiving antiretroviral therapies because you know the blood level that was effective in the patient before they got on antiretroviral therapies.

Slide 49. Patients that may need psychiatric consultation or referral

I always like to state the caveat that although I want primary providers and HIV providers to treat major depression, there are a number of patients who really need emergency consultation or need consultation in order to be adequately treated. Patients who have suicidal thoughts or a suicide plan should be treated emergently by a psychiatrist or a specialized mental health professional. Patients with a history of bipolar disorder or a history of manic episodes should probably be treated by a subspecialty person rather than by a general medical provider. It is possible that you will discover this by accident by giving someone their first episode of bipolar disorder or mania when you start them on an antidepressant. Again, this is a situation in which you need the help of a specialized professional.

Patients who have psychotic features, patients who have more than one psychiatric disorder, patients who have a variety of self-destructive behaviors and personality problems, and patients who have failed more than two trials of antidepressant therapy are also patients who should be referred to subspecialty mental healthcare professional.

Having said all that, subspecialty mental healthcare is not always available, particularly in certain rural environments. In certain inner-city environments mental healthcare can be very difficult to come by. In those settings, there are resources to help providers with chronically mentally ill patients with particularly difficult cases. I urge you to get to know some of those resources. I have done a number of things to try to get those resources out in the community. But the American Psychiatric Association publishes guidelines, a number of books and articles have been written regarding treatment of patients with chronic comorbid psychiatric disorders and HIV, and there are lots of resources for patients if they really need them.

Slide 50. Personality traits may impact adherence and risk

I have talked a little bit about major depression in patients who come with a psychiatric disease state. I want to talk for a minute about personality traits and the way they can impact both adherence and the experience of providers who are treating patients.

You can divide patients up into two broad categories based on temperament or the kind of person they are. One group you might call introverted people and they are people who tend to be more consequent avoidant and less reward sensitive. They tend to be less vulnerable to risk behaviors and if they are infected, they are more likely to have some other psychiatric comorbidity. Their barriers to treatment tend to be anxiety, rumination, and ambivalence.

On the other side of the slide, I have the extroverted person. These patients are more consequence insensitive and reward seeking. They are more vulnerable to risk behaviors and impulsivity. They are more vulnerable to substance abuse. The barriers to treatment tend to be impulsivity, their focus on their feelings, and their focus on now. These personality features have been shown to have profound effects on both people getting infected with HIV and their ability to accept treatment.

Case Study

Slide 51. Case study: Effects of depression on ability to adhere to HIV treatment

I am going to show you a brief case of a patient with major depression and describe some of the difficulties in treating this patient. This is a 38-year-old single male with a long history of chronic gastrointestinal pain, HIV, and anxiety. At his initial evaluation, he complained of low mode, weepy feelings, and indecision about HIV since his diagnosis 5 months earlier. His CD4 count was 400 at his initial presentation. His viral load was 68,000. He discussed potential pitfalls in every treatment option for over an hour at his initial interview, and had been clearly encouraged to consider HIV treatment by his primary provider, but was extremely reluctant to initiate care.

Slide 52. Effects of depression on ability to adhere to HIV treatment (cont’d)

He was initially treated with fluoxetine and stated that it helped him, but discontinued it because his GI pain had gotten worse. He later complained of worsening depression and tried a series of nine different antidepressants, all of which he said made his GI pain worse. He continued to come for treatment complaining that he was having sexual dysfunction but was unable to tolerate any antidepressant.

Slide 53. Effects of depression on ability to adhere to HIV treatment (cont’d)

At this point, what would you do to treat this guy? Would you restart his antidepressant therapy? Start antidepressant and HIV therapy? Counsel the patient for depression and conduct the follow-up visit in a few weeks? Or start the patient on antiretroviral therapy and refer him for depressive counseling?

Slide 54. Effects of depression on ability to adhere to HIV treatment (cont’d)

Over the next period of time the patient continued to come intermittently for treatment. His CD4 count fell to 300 and he was offered antiretroviral treatment by his primary provider. He ruminated about the decision for more than a year and finally began treatment when his T cells fell 220 cells. He discontinued treatment promptly because his medication made his GI pain worse. He underwent a course of treatment for helicobacter pylori even though he did not have any evidence of infection. He said that his pain improved quite considerably while being treated for Helicobacter pylori, but his pain promptly worsened when antiretroviral therapy was reintroduced.

Slide 55. Effects of depression on ability to adhere to HIV treatment (cont’d)

Over the next two years his CD4 count gradually declined until he had 8 T cells/mcL. He was admitted to the hospital for PCP and hypoxia. Following his discharge, he was admitted to the psychiatric service where he took antiretroviral therapy perfectly for 8 days with absolutely no GI symptoms. He then demanded to leave because he was bored and he stopped his antiretroviral therapy within days of his discharge because of worsening GI pain.

Slide 56. Effects of depression on ability to adhere to HIV treatment (Cont’d)

After several weeks of going back and forth, he finally signed a treatment contract stating that he could see his doctor only if he was taking all of his medications and he agreed to discuss his medications at each visit before discontinuing them. In the face of this treatment contract, he was unable to contact anybody to discuss his GI pain unless he came to the clinic and was taking his medications. Because it was so important to him to discuss his GI pain and because it was so important to him to see his doctors to ruminate over whether or not his antiretroviral therapy was worsening his GI pain, he took his medication so he would have access to his physicians in order to discuss this. This resulted in successful treatment with antiretroviral therapy. The patient is seen each week and complains of GI pain but has been stable for 3 years with no change in his antidepressant therapy and a couple of changes in antiretroviral therapy. But he remains stable and his T cells have recovered very substantially.

It is obvious that this patient suffers from both depression and personality features that interfere with his treatment. By combining his psychiatric and HIV treatments and collaborating between his psychiatric care provider and his HIV provider, his treatment ultimately was able to become successful.

It is important to know that coherent psychiatric and substance abuse treatment, as well as HIV treatment, have a profound impact on outcome.

Slide 57. Depression in HIV-positive women and in men: WIHS and MACS cohorts

This next slide summarizes some cohort studies that have shown that treatment is important in terms of virologic outcome. In the Women's Interagency HIV Study (WIHS), virologic response, immunological response, and clinical response were predicted by continuous use of antiretrovirals, a lack of depression, and by current drug use. In another analysis of the WIHS study data, there was an increased probability of antiretroviral utilization for women who were identified as depressed if they received antidepressants and mental health therapy or mental health therapy alone, but not antidepressants alone. This demonstrates the importance of having psychotherapy involved in the treatment of every patient. It also shows how important it is that a psychotherapist or a specialty mental health person or a trained HIV provider with mental health experience is involved in patients who need treatment.

In the multicenter AIDS cohort study (MACS), interruption of antiretroviral therapy was predicted by age, race, geography, viral load, depression, time on HAART, low adherence, and a lack of lamivudine in the regimen. Discontinuation of antiretroviral therapy was predicted by age, viral load, depression, and abacavir or lopinavir use. So both drugs, psychiatric disorders, and the integration of treatment all have a profound effect on outcome.

Slide 58. Relationship between antidepressant use and adherence

There are a number of studies looking at the relationship between antidepressant use and adherence. In a retrospective study, shown in this slide, of 1,713 HIV-infected patients in an urban healthcare setting, 57% of the patients were depressed. Of those depressed patients, 46% received antidepressant therapy and 52% received antiretroviral therapy. The antiretroviral adherence was lower among depressed patients not on an antidepressant but better amongst patients on an antidepressant. Nonadherence to the antiretroviral therapy was more likely to occur in patients nonadherent to the antidepressants and in patients who used alcohol.

This study shows that it is important to get patients to take their antidepressants And that there is a direct association between taking antidepressants and good adherence to antivirals.

Slide 59. Alcohol consumption and adherence

There is also a temporal and dose association between alcohol consumption and adherence. In the next study, the VA Cohort Study of 2,702 patients, 56% of these patients who were abstainers missed doses on 2.4% on all days surveyed. Thirty four percent of the patients were nonbinge drinkers and on drinking days their missed doses went up to 3.5%. On their post-drinking days, their missed doses were 3.1%. On their nondrinking days, they had the same kind of adherence as patients who were abstainers. Finally, 8.9% of the patients were binge drinkers and during drinking days they missed 11% of their doses, and post drinking days, 7%. Even during their nondrinking days, they were much more likely to miss their medications than patients who were abstainers.

Slide 60. Overcoming psychiatric barriers to adherence

So what do we do to overcome the psychiatric barriers to adherence? The first thing we have to do is diagnose and treat major depression. We have to manage personality problems and manage temperament problems. We have to treat addictions when we find them and make sure patients have comorbid treatment. We have to develop a therapeutic alliance that allows patients to develop therapeutic optimism, and look at their lives, and encourage them to change those lives in ways that can allow them to have a better outcome.

Slide 61. The power of psychiatric treatment

The last study is a study recently done by Seth Himelhoch and was published in JAIDS. I will not take you through the details of this study, but just show you the conclusions.

Seth studied a cohort of patients in the HIV clinic at s Hopkins who had received psychiatric treatment and compared them to a group of patients who had never received psychiatric treatment and had no diagnosis of a psychiatric disorder. Patients who were identified as psychiatrically ill, and received at least one visit to psychiatry and were treated at least once with a psychiatric medication had a 40% reduction in mortality. Although much of this was accounted for by better treatment of their HIV, it is clear that the better treatment of their HIV was a direct outcome of their psychiatric treatment. A 40% reduction in mortality is a profound finding. It is certainly a profound finding in a group of patients who have been seen as the discard pile in terms of patient care. It is more difficult for patients with psychiatric disorders and substance abuse disorders to access medical care, particularly more difficult for them to access HIV care, and the care is often provided in fractured and unstructured ways in a variety of different clinics. Patients are often referred to many different facilities to receive their various treatments, and this results in poor outcomes. In this integrated clinic that Seth Himelhoch studied, you can see that there is a profound impact on mortality by integrating substance use disorder treatment, psychiatric disorder treatment, and HIV treatment under one roof.

Slide 62. Poor adherence

Finally, I want to mention that patients with poor adherence need an assessment of their comorbid disorders, education, treatment plan induction, and medication adjustment. At that time, they will have better adherence and improved self-efficacy, at which time you can engage more aggressive therapies such as antiretroviral treatments and collaboratively treat their comorbid disorders, and ultimately have better outcomes.

Conclusion

It is important to know that treatment of HIV is not a hopeless task. This epidemic can be stopped and we can stop it. But the only way we are going to stop it is by treating the disorders that drive nonadherence and infection in patients with HIV. A good portion of those disorders are psychiatric and psychological. And a good portion of those disorders involve substance use. It is incumbent upon us, as a community of HIV care providers, to demand better resources for our patients with psychiatric disorders. It is incumbent upon us to raise a little hell and for us to go out and fight for the rights of our underprivileged and underserved patients so that they can have a 40% or better improvement in mortality. It is too profound to ignore. It is cost effective and the reason we are not doing it is because of discrimination.

I urge all of you to take a little action and to give people a hard time about not treating these patients. Get the resources, get the time, and help the patients get better. I hope this was an enjoyable presentation for all of you. I thank you for joining me and I look forward to our further interactions.

Authors and Disclosures

Regards, Vergelpowerusa dot org"I learned that...no one is perfect but most people are good; that people can't be judged only by the worst or weakest moments; that harsh judgements can make hypocrites of us all; that a lot of life is just showing up and hanging on; that laughter is often the best, and sometimes the only response to pain." My Life by Bill ClintonAOL now offers free email to everyone. Find out more about what's free from AOL at AOL.com.