Advances in Treatment of Psychiatric Disorders in Patients with HIV

Abstract

Psychiatric disorders have been shown to be risk factors for infection with HIV but have also been shown to be consequences of HIV infection, as well as barriers to effective care. Psychiatric disorders are associated with poor treatment outcomes, increased morbidity and mortality. Integrated care in clinics where mental health services are combined with psychiatric services has been shown to be effective in overcoming these issues. Major depression is a common psychiatric disorder in HIV patients at a 3-5 fold increased prevalence over background rates. Major depression increases the risk for infection but has also been shown to be a consequence of viral brain injury. Major depression is a barrier to successful treatment of HIV. Bipolar disorder has similar associations, but the data is weaker. Personality disorders are a risk factor for HIV infection, cause frustration for clinicians and are associated with poor treatment outcomes. This issue can be mitigated by integrated care of patients with this co-morbidity. Substance use and addiction are fundamental factors in HIV transmission. They are often encountered in clinics that treat HIV, but are often a barrier to care because of the lack of expertise in treating these conditions. Numerous psychological stressors are associated with HIV infection. Stigma, Post Traumatic Stress Disorder (PTSD) and disenfranchisement from medical care are surmountable barriers when psychiatric care is integrated with medical care. HIV populations are often underserved and impoverished and cutbacks in coverage for medical care will sabotage the efforts to eliminate HIV infection.

Introduction

Psychiatric disorders occur at higher rates in patients infected with Human Immunodeficiency Virus (HIV) than in matched uninfected people, and psychiatric disorders complicate the diagnosis, treatment, and outcome for this population. In the course of the 40 years since the discovery of the epidemic, research has shown that psychiatric disorders play a role in the risk behaviors for getting infected, are barriers to effective diagnosis and treatment, and complicate the ability of clinicians to effectively engage with patients. Infection with the virus has also been shown to increase the risk for development of psychiatric disorders, to cause stigma and marginalization of infected patients, and to increase the psychological distress and dysfunction associated with living with HIV infection. We will organize this review around the psychiatric conditions that have been identified in HIV-infected patients with updates on newer research and clinical care. It will also highlight the challenges faced by the current medical system to effectively counter the epidemic. We will discuss psychiatric diseases such as major depression, bipolar disorder, schizophrenia and cognitive impairment first, followed by a discussion of substance use disorders, problems of temperament and personality, and finally problems that emerge from life experiences, coping issues and traumatic events.

Acquired Immuno-deficiency Syndrome (AIDS) was described in the early 1980’s as the cause of death (due mostly to opportunistic infections) of young, otherwise healthy people that appeared to be spreading in an epidemic fashion. Victims shared a characteristic of regular intimate exposure to others through sex, shared needles or blood transfusions. Human Immunodeficiency Virus (HIV) was identified as the cause of the illness and is a single-stranded, positive-sense, enveloped RNA virus that must undergo “reverse transcription” into double stranded DNA molecules to be infectious (a retrovirus). It infects cells displaying specific receptors, (generally CD4), found on lymphocytes, macrophages and reticular cells. The virus is transmitted only when competent viral particles or infected cells are directly exposed to immune cells. The virus is also transmitted vertically from mother to child via breast milk or during exposure to maternal fluids during delivery. Once infected, the immune system attempts to destroy infected cells leading to a war between the virus and the immune system that results in a gradual depletion of the immune system. This process occurs over about a decade for the average patient but can be affected by many factors. The result is immune deficiency and death unless the person receives treatment.

Remarkable progress has been made in understanding the viral life cycle, developing effective treatment with medications that suppress viral replication, and now with medications that can protect uninfected people from transmission. Several classes of antiviral drugs have been developed, and when given in combined cocktails lead to complete suppression of viral replication by targeting different elements of viral replication. Curative treatment appears to require complete eradication of integrated virus in dormant immune cells. This has only been achieved in a few very specialized cases when treating cancers by bone marrow transplantation. Cessation of treatment in most people leads to re-emergence of virus in the blood and eventual loss of an effective immune system. Effective vaccine development has failed thus far because of several unique elements of the virus. Prevention of infection, termed Pre-Exposure Prophylaxis (PrEP) is virtually 100 % effective when used properly. Most recently, very long-acting injectable HIV treatments have been developed that can last months (or possibly longer) and effectively treat as well as effectively prevent infection.

Because the virus is mostly transmitted by specific behaviors, (sex and needle sharing), a public health campaign was directed at stopping the “high risk behaviors” that transmitted the virus. Consistent use of condoms and clean needles almost completely abrogates transmission of HIV, but despite efforts to promote “safe sex” and clean needle use, viral transmission continued at high rates into the 1990’s. Investigations in the late 1980’s and 1990’s showed that behaviors causing high risk for HIV transmission were frequently associated with psychological and psychiatric conditions. Clinics specializing in HIV infection found the prevalence of psychiatric disorders was unexpectedly high. The clinic at Johns Hopkins reported very high rates of psychiatric disorders in our new intakes in the late 1980’s and early 1990’s and we described psychiatric disorders as vectors of the spread of the virus [1]. As people with HIV developed immune suppression, they developed a variety of neurological and psychiatric conditions that included Major Depression, AIDS Mania and AIDS dementia. Psychiatric disorders interfered with the delivery of care for patients in a variety of ways and taxed the resources of clinicians and clinics with little experience in the care of psychiatric conditions.

The earliest psychiatric issues in HIV clinics centered around death and dying that appeared inevitable in the late 80’s. Provision of grief therapy, overcoming demoralization, and care for the caregivers to help cope with the deaths of their patients were the focus of mental health providers in HIV clinics. One of the first observations by psychiatric providers was the unexpectedly high rate of psychiatric disorders in HIV clinics. Psychiatric conditions that seemed associated with HIV included mood disorders (both major depression and bipolar disorder), cognitive impairment, substance use disorders, problems of temperament, PTSD, anxiety disorders, and adjustment disorders with extended grief reactions and impaired coping skills [2]. In this setting, the presence of mental health providers in HIV clinics improved care dramatically for the patients and the morale of HIV clinicians [3].

Mood Disorders in patients infected with HIV

Mood disorders, particularly major depression and bipolar disorder, are well described conditions in which the baseline level of reward, pleasure or enjoyment are altered, usually along with a sense of decreased or increased mood, energy, vitality, capacity and drive. In the early days of the HIV epidemic, depression was thought to be an understandable reaction to having a fatal illness and was usually treated with supportive therapy, but on closer examination there appeared to be both an increased incidence of demoralization related to the diagnosis and an increase in the prevalence of major depression. HIV continues to be associated with increased rates of major depression [4]. Numerous studies showed that people with major depression had an increased likelihood of getting infected, but as the HIV infection progressed there was an associated increased risk of developing Major Depression de novo. People with depression had less frequent sex but more risky sexual behaviors when they had sex. Patients with addiction to IV drugs and depression had more needle sharing, and patients with addictions without needle use also had more high-risk sexual behaviors than those with depression. Although rates of major depression varied across studies using different methods of ascertainment, there appeared to be a 3-4-fold increase in major depression in patients infected with HIV. Studies of treatment suggested that patients responded to antidepressants similarly to uninfected populations, and that all effective treatment modalities (including ECT) were effective [5]. Several of the medications used to treat HIV were associated with the development of major depression as well, and this appeared to vary considerably with different antiviral drugs (see below).

Because most clinics for HIV care have limited access to mental health provision, major depression is underdiagnosed and under-treated, a circumstance that is an ongoing problem almost 40 years later, and patients with HIV are still less likely to have optimal adherence to antidepressants when they are treated [6,7]. Patients with untreated major depression are less likely to seek treatment, less likely to take adequate treatment, more likely to drop out of treatment, have more co-morbidity, and are more likely to die than those without depression. Education of HIV clinicians about how to diagnose and treat major depression has led to more recognition and treatment, but underdiagnosis and undertreatment remain a serious problem. Treatment of HIV-infected patients with antidepressants is usually straightforward and investigations have shown effectiveness and cost-effectiveness with improved outcomes.

There are similar findings with bipolar disorder, but the data is weaker. Early in the epidemic a specific form of mania referred to as AIDS Mania was described which differed from idiopathic bipolar disorder being specifically associated with late-stage infection and with HIV Dementia. Cases now are very rare as treatment of HIV is improved and rarely progresses to the extent that is required for AIDS Mania to occur. Treatment of bipolar disorder in patients with HIV is similar to those without HIV with the caveat that some medications used for treatment of bipolar disorder have interactions with antiretroviral drugs.

Patients with HIV are less likely to obtain treatment for major depression, and patients with social barriers to health care are less likely to get treated for depression. This has been the case throughout the epidemic, and despite efforts to overcome barriers, this continues to be the case. Racial, economic and social disparities are associated with inadequate treatment of depression. Older patients are adversely affected as well [8]. More recent research continues to confirm these findings and has broadened to include many developing countries, rural and hard to reach populations, and older people living with HIV. Recent studies also demonstrate the association between depression and alcohol, opiate use, stimulant use, stigma, social isolation, disenfranchisement, and poor access to health care. [9,10,11,12]

Several factors are associated with depression in patients infected with HIV. A history of pre-existing depression is an obvious factor, but inflammation, dysbiosis, immune reconstitution (with the attendant increase in inflammation), HIV medication toxicity, as well as numerous other proposed mechanisms have been implicated. There is an association between several inflammatory markers and increased risk for depression. Additionally, certain HIV medications have been associated with new onset of depression. The early nucleoside inhibitors of reverse transcriptase (particularly Didanosine (ddI) and Stavudine (d4T)) had mitochondrial toxicity and caused neuropathy and depression. Zidovudine (ZDV), also known as azidothymidine (AZT), the first drug widely used for HIV, was also associated with depression.

The advent of protease inhibitors and non-nucleoside reverse transcriptase inhibitors (NNRTI’s) led to the breakthrough of HAART (highly active antiretroviral therapy) and the effective conversion of HIV from a universally fatal inevitably progressive disease to a chronic illness. One of the most effective NNRTI’s, efavirenz, had a clear association with depression in some patients, a fact debated hotly for several years until the data became overwhelming. The newer class of integrase inhibitors are also associated with depression. Although many of these cases respond to treatment with antidepressants, some cases required a change of antivirals to another agent or class of agent for the depression to resolve. Several “switch” studies showed benefit to changing antivirals in some patients.

Most recently, long-acting injectable antivirals which require only monthly (or even less frequent) administration have been developed. Injections of combined cabotegravir and rilpivirine can be once every two months, and injections of lenacapavir may be once every six months (although for treatment in infected patients lenacapavir still requires the use of oral medications). Use of these drugs has several additional considerations, but they appear in early studies to be very effective in both treatment and prevention. Another major development in HIV prevention is the use of pre-exposure prophylaxis, a regimen of antiviral drugs that can effectively prevent infection. Initially a combination of two drugs given daily, the long-acting drugs are also being used for prevention, obviating the need to take any medications other than infrequent injections.

Treatment of depression in patients follows the guidelines for idiopathic depression with several caveats. Higher rates of co-morbidity (chronic pain, diabetes, hypertension, renal disease, liver disease and numerous others), as well as an aging population of HIV infected patients and frequent polypharmacy makes thoughtful treatment important. Possible benefits in terms of smoking cessation (bupropion), chronic pain (SNRI’s and TCA’s), insomnia (TCA’s and mirtazapine), stimulant use (mirtazapine and topiramate) may affect the choice of antidepressant medications. SSRI’s may have some benefit in terms of HIV itself [13,14].

With the advent of electronic medical record programs, a blizzard of drug interaction warnings will undoubtably have an impact on prescribing of antiviral drugs. Most of the drug interactions are theoretical and are not the result of careful research and clear blood level measurements and toxicity assessments. Weighing the electronically generated warnings, which include no references and have unclear origins, with the benefits of a particular drug or class may cause discomfort for clinicians trying to choose what is in the best interest of the patient. Articles critical of the proliferation of poorly thought-out autogenerated warnings make for valuable reading [15].

For primary providers in HIV clinics, most of us recommend getting to know an easy-to-use SSRI or two, and then adding other antidepressants as time goes by, and then getting consultation for patients who do not respond. Experts will try to use drugs where the side effects work for the patient. Constipating drugs for patients with chronic diarrhea, sedating drugs for patients with insomnia, drugs that are more anxiolytic for patients with severe anxiety, and drugs that have kinetic properties such as long half-lives for patients who are likely to miss doses frequently. Choices of bipolar treatment are more complicated as lithium can be an issue in patients with renal impairment, and Valproate can be an issue in patients with liver disease and deficiencies of hematopoiesis. Anticonvulsants in general have more drug-drug interactions than antidepressants, and carbamazepine has several notable interactions with HIV medications. Because drug levels are available and meaningful in antiepileptic medications, these can be monitored for drug interactions. The changes in metabolism of antivirals is more complex, but even in very difficult cases monitoring viral loads and levels will usually make it possible to effectively treat patients.

Schizophrenia and Chronic Mental Illness

Early in the HIV epidemic, Dr. Francine Cournos and others noted that patients with schizophrenia and other chronic mental illnesses were at increased risk for HIV infection [16]. Psychiatrically ill patients were vulnerable to coercive sexual behaviors that were risky for sexual transmission of the virus, and those with addiction had more risk behaviors associated with getting and using drugs. These patients were marginalized in terms of obtaining medical care, and many clinics found the additional time and resources for the care of patients with chronic mental illnesses extremely burdensome. The stigmatization of chronic mental illness and the strong division between psychiatric clinics and medical clinics made it difficult for these patients to access treatment. HIV clinicians receive little training in mental health care, and psychiatric providers had little knowledge of HIV and available treatments. Some clinics experimented with integrated treatment, and this has been found to be essential in the care of these patients. The model of integrated care we demonstrated early in the epidemic has been extensively researched in many settings by Brian Pence, Greg Lucas and others showing effectiveness and cost effectiveness. Studies in other countries and in other conditions have continued to show the value of this model [17,18].

Treatment of chronic mental illness with extended action depot neuroleptics is a useful element, but it is equally important to provide adequate medical care. The outcome for chronically mentally ill patients infected with HIV is higher mortality and morbidity than in other populations and inadequate treatment is a vector for the ongoing spread of the virus. As this population ages, it is even more critical that integrated care provides a way to prevent the serious morbidity increasingly experienced by these patients. Primary medical providers are often overwhelmed by the needs of chronically mentally ill patients, and psychiatric providers may be overwhelmed by the medical needs of aging HIV patients. Our patients often see their psychiatric providers far more often than their primary medical provider and interventions in diabetes, renal and hepatic disease, heart disease and early detection of cancer and dementia lead to saved dollars and better outcomes. The aging population is also vulnerable to substance use even in patients without prior use. Having psychiatric providers, substance use programs and HIV and Hepatitis care in the same clinic allows for better communication and better outcomes and disease prevention.

Disorders of Temperament and Personality

Unlike diseases that afflict an individual, such as depression and bipolar disorder, temperament and personality define the characteristic or usual way people respond to situations in life. While not always predictable, people do have a characteristic way of responding to problems, circumstances and environmental stimuli that allow us to “know” them. As part of the personality, people have underlying “dispositions”, ways that they are disposed to behave, think, feel and act. These dispositions have been the subject of much research, and a variety of factors or traits have been identified that describe the cognitive, affective and executive dispositions of populations. Temperaments can cause disorder in people with intense endowments of traits when faced with situations where those traits are detrimental. Researchers who study personality generally agree that there are no “bad” traits, but instead traits are beneficial in one set of circumstances and detrimental in the opposite circumstances.

These traits, such as height, IQ, or musical talent, are described as being dimensional and are “normally” distributed in the population. Efforts to make these dimensions of people categorical, such as tall, average and short are arbitrary, as are the cutoffs for IQ in the definitions of mental subnormality, borderline intellectual capacity, average, above average and genius. Cutoffs based on standard deviations from average have been used to define clinical categories as in IQ; two standard deviations below the average score, an IQ of 70, is defined as mental retardation or subnormality, although there is no meaningful difference in an IQ of 69 and an IQ of 71. Traits such as warmth, sociability, cheerfulness, optimism, maturity, mathematical ability, organization, and leadership can be described this way. The issue of nature and nurture in personality is still heavily debated, but at least some elements of temperament have been shown to be responses to circumstances encoded before birth and are part of the “nature” of a person.

Personality can be defined as the characteristic way of relating to the world combining underlying disposition and learned responses to circumstances. Personality encompasses a person’s typical thoughts, emotions, and behaviors, particularly behaviors in response to problems or circumstances. There are several models that describe fundamental traits of personality, but we have found a model derived from work by Hans Eysenck and Sybil Eysenck [19] particularly useful. The model we favor focuses on a normal distribution of two continua, introversion vs extraversion and stability vs instability (Eysenck used the term neuroticism instead of instability). We have found this model to be clinically useful in working with patients with personality traits that interfere with clinical care. It has also been useful in helping non-psychologically trained clinicians understand problems of personality in the clinic.

The Introversion vs Extraversion Dimension

The continuum of introversion to extraversion (See Figure 1) describes the factors that are most salient to a particular personality on a continuum. One extreme of the curve describes people who are extremely introverted and at the other end people who are extremely extraverted. The majority of the population falls somewhere between these extremes. Carl Jung’s conceptualizations from the early 1900s defined introversion as an “attitude type characterized by orientation in life through subjective psychic contents” (focus on one’s inner psychic activity) and extraversion as “an attitude type characterized by concentration of interest on the external object” (focus on the outside world) [20]. Extraverts tend to respond to stimulation or emotional provocation with excitation, while introverts respond with inhibition. At the extraverted end of the population curve, people are more sensitive to rewards and less avoidant of consequences, sensitive to the present rather than the future and past and prioritize feelings over function. These traits help with tasks such as performance in front of others, sales, political work, and social functioning. While these traits are useful, they may also convey vulnerability. It is easy to see how this type of person may be vulnerable the rewards of intoxication, impulsive sexual behaviors, risky activities associated with HIV transmission such as needle sharing, and other behaviors. It is also easy to see how these patients might frustrate clinicians who are focused on avoiding consequences, trying to improve for the future, and focused on function. At worst, these patients are described by doctors in pejorative terms as being uncooperative and as being clinically difficult to manage. At the other end of the curve are the introverted people who focus on avoiding consequences, maximizing function, and directing their attention to the future rather than the present. They excel at tasks that prioritize details, potential consequences and investment in the future. They make good internal medicine doctors, accountants and scientists. They are vulnerable to anxiety about uncertainty, missing opportunities, and a tendency to potentially miss out on pleasures of life. It is easy to see how this would also predict some conflict between the introverted clinician and the extraverted patient [21].

Fig 1.

Diagram based on The Psychiatry of AIDS: A Guide to Diagnosis and Treatment; Treisman, GJ, and Angelino, AF, Johns Hopkins Press 2004

The Stability vs Instability Dimension

The other dimension we focus on is the dimension of emotional stability-instability. Stable people have emotional responses to stimuli that are predictable and have a modest maximum level. For them large stimuli produce small emotional responses. Unstable people have a large emotional range, have emotional responses that are variable for a given stimulus and unpredictable, and small stimuli may produce very large emotional responses (Fig 2). Eyesenck used the term neuroticism in place of instability which is interpreted by many as pejorative, however we see instability is a neutral trait like all others. It is useful in many circumstances, allowing people to be emotionally responsive, empathetic, and able to manipulate the emotions of others. It tends to be problematic only for individuals with extreme endowments where emotional responsiveness can create vulnerabilities. Excessive stability can produce emotionally flat people with an inability to understand the emotions of others, poor empathy, and even emotional coldness. People who find emotions salient (extraverts) with extreme stability may resort to extreme behaviors and stimuli to try to achieve emotional experiences. This can include high risk sexual and drug using behaviors, violent behaviors and other risk-taking behaviors. They also have less motivation to seek out help or treatment and may not come to clinical attention until their circumstances are catastrophic.

Fig 2.

Diagram based on The Psychiatry of AIDS: A Guide to Diagnosis and Treatment; Treisman, GJ, and Angelino, AF, Johns Hopkins Press 2004

More frequently, however, emotional instability is a risk factor for infection transmitting behaviors. Extreme emotional instability is associated with higher occurrences of risky behaviors, including unsafe sex practices and addiction. Under the influence of intense emotional states, all manner of intoxication, poor judgment, initiation of or rejection of romances, may occur with these patients, who often have poor coping skills for dealing with the intensity of their emotional states. Emotional instability is often characterized by unstable interpersonal relationships. It can be difficult to form stable medical relationships with those who have an extreme endowment of instability. The emotional instability of these patients leads to sudden intense new relationships that may have medical consequences, and the sudden dissolution of stabilizing relationships that have been helpful in caring for the person.

Another serous potential issue is the difficulty of detecting mood disorders in patients with personality issues. Because of the emotional turmoil these patients struggle with, one can miss depression or even bipolar disorder in these patients. In many clinical settings we prefer to find a single diagnostic condition as an explanation, but co-morbid conditions which exacerbate each other is more the rule in patients with chronic illness. It is important to evaluate personality disordered patients for occult mood disorders.

The endowments of introversion, extraversion, stability and instability appear to be independent, leading to four quadrants of personality types that mirror the four humors the Greeks described thousands of years ago. The most problematic group for clinicians are unstable extroverts, who find emotions very salient and experience them very intensely. They also live mostly in the present and have difficulty recognizing potential consequences in the future or positive experiences in the past. They find getting what they want now very salient and have surges of emotions when frustrated that are difficult to redirect using logic and cognition. Thomas Sydenham is famously quoted as saying, “They love without measure those they will soon hate without reason” when describing these patients. These patients may have a long experience with a clinician that is positive but then suddenly reject the clinician when they are not able to get what they want (usually something that they feel they need). Many clinicians describe these patients as difficult and even hateful [22].

Care of patients with difficult personalities

While a comprehensive discussion of the treatment of personality disorders is beyond our scope, we will discuss several useful caveats in treating these patients. We recommend explaining in non-pejorative terms that these patients have an additional endowment of feelings beyond average, almost like being “a genius of feelings”. One of the issues these patients struggle with is that the intensity of feeling they experience is not the experience of other people. We explain to them that we do not have a medication to decrease their feelings, but that we would not want them to take such a medication as it would dimmish one of their unique gifts. Instead, we will coach them on ways to keep feelings from running their life. Exercises using cognitive-behavioral therapy approaches, such as Linehan’s Dialectical behavioral therapy can be very helpful for clinicians managing these patients [23].

Many clinicians complain of difficulty tolerating the feelings of distress these patients engender in them. As expert readers of the emotional states of others, patients can effectively overwhelm clinicians in order to achieve their goal, which may be to cause distress due to their own sense of boredom or anger. It helps many to recognize that this has nothing to do with the clinician and is due to and associated with the patient’s personality.

Addictions in the HIV Clinic

There is a complex matrix of terms for the behaviors associated with the ongoing use of reinforcing substances that come to impair judgement and function in all areas of life. These terms include addiction, substance abuse, substance use disorder, substance dependence, substance misuse, heavy substance use, alcoholism, and many others. This plethora of names reflects the complicated agenda of avoiding stigmatizing patients while stigmatizing behavior, avoiding pejorative terms and at the same time reflecting the socially damaging nature of the problems. Involved in the evolution of the names for the illness is the denial phase of the disorder, during which people say “I am not an addict” or “I am not an alcoholic” or “I can quit anytime I want”. This has been further complicated by the fight between those who intractably maintain that using drugs is a choice and that people can “just say no” to those who intractably maintain that this is a disease and that there is no volitional component to the disorder. The reality from those who study the condition is that the disorder is a set of behaviors that have been conditioned toward becoming automatic and habitual and are associated with a “drive” for rewards and are neither simply a choice nor a simply an involuntary action. For these reasons we will interchangeably use the term that the patients themselves choose, “addiction”, and the term that many researchers favor, “substance use disorder”. Terms such as physical dependence, conditioned withdrawal and conditioned craving will be used only as needed for clarity.

The use of alcohol, marijuana, cocaine, opiates, and benzodiazepines have all been described as “recreational” under some circumstances, and this term is used in opposition to the term substance use disorder. The question of recreational use as opposed to addiction can be a difficult call to make, but in general, addiction is associated with increasing use despite increasing consequences that begins to disorder function. The continuum on which casual use becomes regular use and then becomes excessive use makes it difficult for people to say when someone has crossed the line to addiction. Patients seldom deny that they have cancer, pneumonia, or renal failure, but often vehemently deny addictive behaviors. The use of motivational interviewing, gentle confrontation, more forceful confrontation and other techniques is promulgated to help patients recognize the severity of their problem. Because of the tendency to under-report drug use, urine toxicology screens and alcohol metabolite measurements are often helpful in making the diagnosis. Ultimately, a relationship between the clinician and the patient is essential for effective diagnosis and treatment.

The multifactorial matrix of influences that initiate, drive, and sustain substance use and addiction is beyond our scope. The intrinsic rewarding effect of the substances themselves, mood disorders, issues of temperament, issues of life experience, and coping skills all play a role in the vulnerability to developing addictions. Individual biology is involved in several ways. In the case of alcohol, genetic factors may affect the degree to which alcohol is rewarding, while genetic influences on risk taking and other features of personality may play a role in stimulant and opioid use

The obvious associations of substance use disorders with HIV, including transmission by needle sharing, association with other people with addictions leading to sexual transmission, the high-risk sex associated with prostitution for the purpose of obtaining drugs, the high-risk sexual behaviors associated with being intoxicated, and the barriers to medical care associated with living with addiction have been described. Additionally, more subtle issues such as chronic pain syndromes associated with HIV leading to opiate addiction, the rise of marijuana prescribing for a host of conditions, and the disenfranchisement of people with HIV or addiction making it difficult to get adequate care all play an addition role in the complex association between HIV and addiction.

Ongoing substance use not only facilitates HIV transmission, it also negatively affects outcomes in HIV treatment. Once infected by HIV, patients are often demoralized, become hopeless, and are more likely to continue using drugs and engage in high-risk behaviors. Patients with substance use disorders may not seek health care or may be excluded from health care because of stigma. In addition, intoxication and the behaviors necessary to obtain drugs interfere with adherence to medication regimens and medical appointments.

Neurological symptoms can overlap between HIV infection and substance use. For instance, both AIDS dementia and drug intoxication can present with apathy, disorientation, aggression, and an altered level of consciousness. Drug withdrawal can present with seizures and neurovegetative symptoms, as can opportunistic infections of the CNS. People who inject drugs and who have HIV tend to be at higher risk of developing fungal or bacterial infections of the brain and spinal cord. HIV-infected patients who drink alcohol, particularly those older than 50, are more vulnerable to cognitive decline and structural brain changes on neuroimaging than patients who are nondrinkers.

A variety of schema for organizing thoughts about what is essential to treatment of addiction have been described. We have found this rubric useful. These are described as steps but often occur simultaneously.

• 1.Role induction and motivation to change
• 2.Detoxification
• 3.Treatment of co-occurring conditions
• 4.Rehabilitation
• 5.Relapse prevention

The initial and often most daunting task of treating the addicted person is engagement and induction of the patient role. The general rule is that people with addictions and treatment providers begin with differing agendas—people coming for care are often seeking crisis relief, whereas physicians and other health care providers look at long-term goals of improvement in the patient's health and overall function. One of the critical initial tasks of the health care provider is to engender the gradual evolution of the patient's acceptance of their role as a person struggling with a potentially fatal disorder and for whom treatment will improve their function, quality of life and longevity.

Prochaska and DiClemente [24] have described a “transtheoretical stages of change” model to explain the addiction and recovery process. Although there have been numerous updates in the original description, the essence seems to be essentially variants on their description. The patient is viewed as progressing through several different stages of change: (1) precontemplation—the patient has no intention to change their addictive behavior; (2) contemplation—the patient is considering change because of the negative consequences of drug use but is ambivalent about it; (3) preparation—the patient shows intention to change and takes initial steps to seek treatment; (4) action—the patient decides to modify behavior, environment and circumstances in order to relinquish the addictive lifestyle; (5) maintenance—the patient works to prevent relapse and consolidate his changed behavior and lifestyle. The clinician's job is to assist the patient in moving from one stage to the next in order to facilitate the recovery process. A technique known as “motivational interviewing” developed by Miller and Rollnick can be used to heighten the patient's readiness to change. Empathy and gentle confrontation are employed to amplify the discrepancy between the patient’s current lifestyle and long-term life enhancing goals.

Detoxification is critical for intoxicated patients to understand and process the cognitive steps needed for recovery. Many HIV positive patients with substance use disorders benefit from a brief hospital stay to stabilize their psychiatric and medical comorbidities. This may be where the initial diagnosis of HIV can take place, and rapid initiation of HIV care and antiviral treatment has been shown to improve outcomes. Drugs that cause physical dependence and those that have withdrawal syndromes should be slowly tapered for the best demonstrated outcome. This can be done either with frequent clinic visits or by hospitalization. There has been no evidence to support the idea that noxious withdrawal during detoxification improves outcome and some behavioral studies suggest that severe withdrawal during detoxification may trigger conditioned withdrawal when exposed to environments experienced during “cold turkey withdrawal”. It should be noted that benzodiazepines, barbiturates, and alcohol can produce life threatening withdrawal and treatment for withdrawal from these substances is much safer when performed in the hospital. Tapers of stimulant drugs may be aided by mood stabilizers, particularly the anticonvulsant topiramate.

Many patients with HIV and addictions have co-occurring psychiatric conditions, which need to be treated in order to maximize adherence and abstinence. Conditions such as major depression, bipolar disorder, and schizophrenia are best managed with pharmacological treatment. Because these patients tend to have multiple medical complications, it is important to remember to start medications at low dosages and to titrate slowly to minimize the risk of developing adverse side effects and delirium.

Disorders of personality can be managed with cognitive-behavioral forms of psychotherapy. People with unstable extraverted temperaments may sabotage treatment including staff splitting, doctor shopping, general nonadherence and manipulative behavior. A documented treatment plan with clear goals agreed upon by all the treatment staff should include firm limit setting and consistency on the part of all health care providers involved. Frequent and consistent communication among all providers during the course of treatment can minimize splitting and address issues of nonadherence as they arise.

Long-term treatment is necessary for patients to begin the process of lifestyle change and recovery since addiction is a chronic relapsing disorder. Addiction requires transforming previously held beliefs, attitudes and personal identity into a new way of life. Group therapy has been demonstrated to be effective for this aspect of treatment. This may involve groups within the clinic or integration with outside groups including 12-step meetings (Alcoholics or Narcotics Anonymous), network therapy, rational recovery, therapeutic community or SMART recovery. Group support often provides newly recovering people with a hopeful view of the benefits to be achieved with recovery. Specific HIV-positive recovery groups are widely available and may be helpful for people with addiction who are uncomfortable with their HIV status in a regular group setting.

Patient individualized therapy should focus on identifying triggers to substance use, on minimizing or decreasing exposure to substances, and on defining a clear plan of action if relapse occurs. It is important to realize that relapse is often the rule and not the exception, and plans should be in place for early intervention. Objective measures such as urine and serum toxicology screens help monitor drug use. Contingency management using a variety of positive and negative reinforcers tied to urine toxicology results has also been shown to be effective in maintaining sobriety.

Individual and family therapies can enhance the effectiveness of treatment but should not take the place of group therapy. In individual treatment it is important that the treatment provider remain flexible in the treatment approach. While regular psychotherapy may work for some patients, others may need a more “hands-on” approach and benefit from being referred to vocational rehabilitation, occupational therapy and social skills training. Treatment failures often result when the therapist has a “one size fits all” mentality and adheres too rigidly to one model of therapy.

Pharmacological treatments are available for alcohol, opioid and nicotine use disorders and should be used as adjuncts to the overall treatment plan and have been shown to be effective. For patients with opioid use disorder, pharmacotherapy or medication assisted treatment (MAT) with opioid agonists has been shown to be highly effective in preventing relapse to opioid use as well as reduction in transmission risk due to shared injection equipment. Treatment with methadone, a mu opioid receptor agonist, has been shown to keep people on treatment the longest, but may be more disordering than other agents. Buprenorphine, a mixed agonist-antagonist, has been extensively investigated and is much easier to use, possibly safer, more convenient, and possibly more protective against overdoses, and is effective but associated with higher drop-out rates than methadone (this is an area of some contention). It is available in several formulations, including an oral co-formulation with naloxone to discourage injection and an injectable slow-release formulation (marketed as SUBLOCADE) that can be given monthly. The opiate antagonist naltrexone, both as a daily oral formulation and as a monthly slow release injection is effective, well tolerated, causes the least interference with function, but has the highest discontinuation rate of the drugs used for opioid use disorders.

Other commonly used pharmacological treatments that can help with substance use disorders include:

• Disulfiram (alcohol) (an aversive reaction to alcohol)

• Naltrexone (opioids, alcohol) decreased craving and reinforcement

• Acamprosate (alcohol) decreased craving and reinforcement.

• Bupropion (tobacco) decreased craving

• Buprenorphine (opioids) decreased craving and reinforcement-partial agonist

• Varenicline (tobacco) decreased craving and reinforcement-partial agonist

• Nicotine replacement (tobacco) decreased craving and reinforcement-full agonist.

While not FDA approved for these uses, we have some experience and some authors advocate

• Clonidine for withdrawal and to reduce the use of opiate and sedative-hypnotic agents (including alcohol).

• Lofexadine (FDA approved for opiate withdrawal) and to reduce the use of opiate and sedative-hypnotic agents (including alcohol).

• Gabapentin (and pregabalin) for reducing use of alcohol, opiates and possibly cannabinoids

• Topiramate: for reducing use of alcohol, nicotine, stimulants and cocaine

There is also increasing work with the so called “psychedelic” drugs as well as others for the purposes of treatment.

Integrating pharmacological treatment into HIV care can result in improved treatment outcomes and patient satisfaction with care. The Buprenorphine-HIV Evaluation and Support (BHIVES) Collaborative was a multisite demonstration and evaluation project funded by the US Department of Health Resources and Services Administration from 2005 to 2007 that examined the integration of sublingual bup/nx treatment into HIV primary care clinics. Patients participating in integrated treatment were 52 percent less likely than nontreated patients to use illicit opioids during each treatment quarter and reported overall decreased illicit stimulant use.

Psychological Problems in Patients Infected with HIV

There are a number of specific circumstances that benefit from psychological expertise in HIV clinical work.

The first is testing for HIV infection. Patients at risk of HIV infection are often reticent to get testing. Surveys suggest they fear the results of the test or are too overwhelmed by the issues of their current life and behavior to present for testing. Pre-test counselling and post-test counselling are essential parts of HIV care, and getting infected patients into treatment immediately upon getting results has been shown to be effective and improve outcome and treatment acceptance. HIV has become a chronic treatable illness. In this setting, it seems more reasonable for patients to get tested and engage in treatment. Nonetheless, survey data shows that many patients at significant risk are not getting tested. Psychoeducational psychotherapy directed at encouraging patients to get tested has been offered to a variety of at-risk populations of patients. The outcomes of these intervention studies show that such psychotherapy does result in patients getting tested, diagnosed and treatment started sooner especially when rapid testing and “same day start” medication initiatives are utilized.

Pretest counselling should also include information on safer sex, safe needle exchange, and other risk-reduction interventions as well as preventative pre-exposure prophylaxis (PrEP). This is because a significant percentage of patients who obtain testing do not return for their results for extended periods of time and sometimes not at all.

Tests for HIV antibody are the most widely used and can yield immediate results but can be falsely negative if the patient is infected but has not yet had time to develop HIV antibodies. Looking for HIV virus in the blood is more accurate but a bit more cumbersome in that it takes time to get the results. Patients presenting immediately after an exposure may benefit from post exposure prophylaxis treatment with ART. It is therefore important to ask patients about recent potential exposures if they come for testing.

It can be difficult to distinguish which came first, the psychiatric disorders, the HIV risk behaviors, the losses and psychological traumas or the impact of having HIV itself. Each of these factors is related to all the others. The DSM approach to categorical descriptions of psychiatric disorders is limited to “Adjustment Disorder” and “Posttraumatic Stress Disorder (PTSD)” for patients living with violence, despair and loss of unthinkable proportion. Unfortunately, the psychological difficulties of living with HIV are infinitely more complex than a simple categorical definition.

PTSD in HIV-infected patients

Patients with HIV report more trauma and more severe trauma than the general population and at-risk controls. They have high rates of PTSD and anxiety, economic and social disenfranchisement and high rates of interpersonal instability. Cognizance of the psychological issues in the care of patients with HIV is essential. The treatment of these problems is well within the scope of most clinicians in our field. The psychotherapy for patients infected with HIV can be broadly divided into three categories:

• 1.Psychotherapy for the problems of life encountered by patients infected with HIV
• 2.Psychiatric treatment for specific psychiatric conditions associated with HIV infections
• 3.Specific psychoeducational and psychotherapeutic interventions associated with specific types of interactions with HIV-infected patients

Psychotherapeutic approaches to problems with coping skills, social isolation, grief, PTSD, intimate relationships, family problems, and many other issues have been described, but these recommendations are quite like those found in patients coping with other chronic medical conditions.

Traumatic events such as those associated with actual or threatened death, serious injury or sexual violence often provoke terror, anxiety, and stress and some individuals develop chronic psychiatrically disabling symptoms now called Posttraumatic Stress Disorder (PTSD). Characteristics of the condition include: 1.) Vivid recollection and re-experiencing the trauma (often in the form of nightmares or vivid flashbacks); 2.) Persistent avoidance of thoughts, places, people or feelings associated with the trauma; 3.) Persistent negative emotional changes often with distortions of the event and its’ significance: 4.) Persistent hyperarousal often including insomnia, irritability and hypervigilance. PTSD has a prevalence of less than 1 percent in the general population and a lifetime prevalence of 1 to 9 percent with a female-to-male lifetime prevalence ratio of 2:1. In civilian populations, rape is the event most likely to produce PTSD, particularly if it occurs before or during adolescence.

PTSD increases the likelihood of engaging in destructive behaviors such as alcohol and other drug use, sexual promiscuity, or prostitution. PTSD is of particular concern in HIV treatment and research because it may engender or exacerbate HIV risk behaviors and worsen health outcomes. Cross-sectional research has shown that symptoms of PTSD have been associated with HIV risk behaviors and markers of HIV progression. Symptoms of PTSD in adolescence have been associated with prostitution, injection drug use, and choice of a high-risk sex partner in young adults. HIV-infected adults who have a history of childhood sexual or physical use have reported engaging in more HIV risk behaviors such as drug use and sexual compulsivity than persons with no history of trauma. A high prevalence (42 percent) of HIV-infected women attending county medical clinics had PTSD symptoms sufficiently severe to meet a diagnosis of PTSD. In patients infected with HIV, traumatic stressors and PTSD symptoms have also been associated with lower CD4 T cell to CD8 T cell ratio at follow-up visits.

Veterans with a diagnosis of PTSD have an increased prevalence of HIV infection, particularly with a co-morbid substance use disorder. Women prisoners with a lifetime history of PTSD are more likely to have engaged in prostitution and receptive anal intercourse prior to incarceration compared to women prisoners without PTSD. These studies show associations but not a causal relationship.

The presence of PTSD in an at-risk or HIV-infected positive individual is of particular concern because of high rates of comorbidity (up to 80 percent) with other psychiatric disorders. Specifically, PTSD is most often comorbid with depression and cocaine/opioid use—both risk factors for HIV. Prior depressive episodes may be either a risk factor for the development of PTSD following a traumatic event or a co-occurring response with PTSD to a traumatic event. Substance use may be either an attempt to “self-medicate” suffering after a traumatic experience or a lifestyle that increases exposure to traumatic events, such as robbery or assault.

HIV at-risk or HIV-infected individuals should be routinely screened for PTSD. Instruments such as the Trauma History Questionnaire and the PTSD checklist have increased detection rates of the disorder. Similarly, any individuals presenting with symptoms of PTSD should routinely be screened for depression and substance use. For HIV-infected individuals with PTSD and another concurrent psychiatric disorder, treatment that simultaneously addresses both disorders is likely to be more effective and practical.

The Role of Psychiatry in the HIV Epidemic

Psychiatric disorders are vectors of HIV infection. Untreated psychiatric disorders are associated with increased risk behaviors, are a barrier to diagnosis of HIV, a barrier to treatment, associated with poor compliance and increased morbidity and mortality, and interfere with prevention. Models have shown that all of these can be overcome with mental health treatment. Integrated care has been the most effective approach, with the best studied models having psychiatric care embedded in the HIV clinics. The development of low risk highly effective prevention (PrEP) means new infections can easily be prevented. Unfortunately, at risk people seldom come to HIV clinics looking for PrEP, and therefore those seeing high risk patients with addictions and psychiatric disorders need to be prescribing PrEP. We have made enormous strides in HIV care, but the presence of psychiatric treatment in HIV clinics is far from standard. With financial support being removed from HIV care and mental health care, there is a lot of concern that our progress in the eradication of HIV may fail. It is both effective and cost effective to treat mental illness, a fact particularly well represented by models of care for HIV patients.

Training for PrEP prescribing is easy and should be done for all primary and mental health providers. Mental health experts must become part of the routine care team for HIV and other infectious epidemics, and this will help not only improve the quality of life for patients, but it will also help with prevention of infection. The integration of substance use care, psychiatric treatment, and care for chronic medical conditions such as HIV and other chronic infections will ultimately decrease costs and eventually serve to eradicate this epidemic.

Author contributions

Dr Glenn Treisman wrote the original manuscript

Dr. Joyce King rewrote the manuscript adding critical ideas and organizational changes

Declaration of competing interests

The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.