OVERVIEW

Once a dread illness that portended certain death after months or years of inexorable decline, infection with the human immunodeficiency virus (HIV) has become a chronic, treatable illness. Well into the third decade of the epidemic, more than 20 medications are currently available that curtail progression to the acquired immunodeficiency syndrome (AIDS)—the end stage of infection that, during the early years of the pandemic, was inevitable for nearly all patients. The advent of highly active antiretroviral therapy (HAART) in 1995 reduced AIDS incidence and mortality rates and increased the life expectancy of patients with HIV.¹

The achievements and successes of the past 25 years notwithstanding, diagnosis with HIV infection still foreshadows an arduous course of frequent examinations, serial monitoring of cell count and viral load, and difficult treatments with potentially disabling and disfiguring adverse effects (e.g., neuropathy and lipodystrophy). Effective treatment is not obtainable in all parts of the world, and, even in countries where medications are available, not all patients have access to them. Depression, anxiety, substance use, and—at later stages—cognitive problems frequently complicate the course of illness and jeopardize therapeutic efforts.

For the reasons listed in Table 57-1, the general psychiatrist—regardless of venue and type of practice—will be called on to evaluate and to treat a fair share of patients with HIV infection. This chapter reviews the epidemiology, basic biology, classification, and diagnosis of HIV infection; a general approach to psychiatric care of HIV-infected patients; psychiatric and neurological disorders common in this population, and their treatments; and special clinical problems encountered in HIV psychiatry.

Table 57-1 Why Are the Principles of HIV Psychiatry Important?

EPIDEMIOLOGY

At the end of 2005, nearly 40 million people worldwide were living with HIV infection.² While the prevalence rate of infection has plateaued, the absolute number of people with HIV continues to rise (Figure 57-1). Africa, especially the sub-Saharan region, remains the epicenter of the pandemic, followed by the Caribbean (Figure 57-2).

Figure 57-1 Global HIV prevalence, 1990–2005.

(Adapted from UNAIDS: 2006 report on the global AIDS epidemic, Geneva, 2006, Joint United Nations Programme on HIV/AIDS.)

Figure 57-2 Global HIV prevalence, 2005.

(Adapted from UNAIDS: 2006 report on the global AIDS epidemic, Geneva, 2006, Joint United Nations Programme on HIV/AIDS.)

In the United States, at the end of 2005, more than 1 million people were living with HIV infection.² Approximately 40,000 new infections occur yearly.³ Of these, in 2004, the largest proportion occurred in men who have sex with men (MSM); 27% occurred in women, mostly through heterosexual contact; and half occurred among African Americans (Figures 57-3 and 57-4).⁴ New cases of and deaths due to AIDS declined sharply in 1996, owing largely to HAART (Figure 57-5).⁵ The sharpest declines were in the MSM and injection-drug-using populations (Figure 57-6).⁵ Between 2000 and 2004, however, while AIDS deaths decreased by 8%, new AIDS cases increased by the same amount.⁶

Figure 57-3 New HIV diagnoses in the United States, 2004, by mode of transmission.

(Adapted from Centers for Disease Control and Prevention: A glance at the HIV/AIDS epidemic, April 2006. Available at www.cdc.gov/hiv.)

Figure 57-4 New HIV diagnoses in the United States, 2004, by race.

(Adapted from Centers for Disease Control and Prevention: A glance at the HIV/AIDS epidemic, April 2006. Available at www.cdc.gov/hiv.)

Figure 57-5 AIDS incidence, prevalence, and deaths in the United States, 1981–2000.

(Adapted from Centers for Disease Control and Prevention: HIV and AIDS—United States, 1981–2000, MMWR 50:430-434, 2001.)

Figure 57-6 AIDS incidence in the United States, by mode of transmission, 1981–2000.

(Adapted from Centers for Disease Control and Prevention: HIV and AIDS—United States, 1981–2000, MMWR 50:430-434, 2001.)

BASIC BIOLOGY

HIV (Figure 57-7) is a retrovirus—a virus containing ribonucleic acid and the enzyme, reverse transcriptase, for replication—that affects the immune system and the central nervous system (CNS), gaining entry to cells (e.g., T-lymphocytes, monocytes, and macrophages) that express the CD4 receptor on their membranes. The life cycle of the virus once inside an infected cell is depicted in Figure 57-8. All of the currently available antiretroviral medications target the three key steps and enzymes in this process: fusion of the virus with the host cell membrane; reverse transcriptase; and protease.

Figure 57-7 Human immunodeficiency virus. PR, Protease; RNA, ribonucleic acid; RT, reverse transcriptase.

(Modified from Cohen J, Powderly WG, editors: Infectious diseases, ed 2, Philadelphia, 2004, Elsevier, p 1252.)

Figure 57-8 Life cycle of HIV.

(Adapted from Cohen J, Powderly WG, editors: Infectious diseases, ed 2, Philadelphia, 2004, Elsevier, p. 1254.)

During the first weeks after infection, the population of CD4+ T-lymphocytes (i.e., the CD4 count) decreases as the amount of virus in the blood (i.e., the viral load) increases (Figure 57-9). Following a weak and short-lived rebound, the CD4 count steadily declines. At the same time, the viral load oscillates around a “set-point” until ultimately viral replication intensifies and peripheral viremia surges. Administration of HAART, when effective, halts this process. Opportunistic infections (OIs), neoplasms, and neuropsychiatric conditions occur with increasing frequency as the immune deficiency worsens; prophylaxis for certain OIs (e.g., Pneumocystis carinii pneumonia and toxoplasmosis) is instituted during the course of infection according to the CD4 count.

Figure 57-9 History of HIV infection with HAART.

(Adapted from Bartlett JG, Gallant JE: 2001–2002 medical management of HIV infection. Available at www.hopkins-aids.edu.)

CLASSIFICATION AND DIAGNOSIS

According to the Centers for Disease Control and Prevention (CDC),⁷ AIDS is defined by a CD4 count below 200 cells/μl (or less than 14% of total lymphocytes) or the presence of an AIDS-defining condition (Table 57-2). This 1993 revised classification established nine possible categories of illness (Table 57-3). The introduction of HAART has diminished the clinical utility of this taxonomy.

Table 57-2 AIDS-Defining Conditions

Table 57-3 Classification of HIV Infection and AIDS

Infection with HIV is usually diagnosed in two steps. The initial test is an enzyme-linked immunosorbent assay (ELISA). A positive result on this test is then confirmed by a Western blot test. Screening used to be recommended based on risk factors for infection, but the CDC is now recommending that HIV testing be done as part of routine clinical care for all patients.⁸ One compelling reason for this change is the high percentage (approximately one-quarter) of HIV-infected people in this country who do not know they are infected.

GENERAL APPROACH TO PSYCHIATRIC CARE

The approach to the psychiatric care of the patient with HIV infection focuses on accurate diagnosis; an appreciation of the differences in response to, and tolerability of, psychotropic medications in this population; and the prognostic importance of optimal adherence to effective antiretroviral treatment, which psychiatric illness often compromises.

Psychiatric symptoms in a patient with HIV infection may be primary or secondary (Tables 57-4 and 57-5); the CD4 count is useful in making this differential diagnosis. A CD4 count greater than 500 cells/μl suggests a primary psychiatric cause, whereas a CD4 count less than 200 cells/μl, and a fortiori less than 50 cells/μl, suggests the psychiatric problem is secondary to the effects of immune compromise. For example, a patient who has just been told that he is HIV-positive but whose CD4 count is still normal and whose viral load is low may become depressed as part of an adjustment disorder (a primary psychiatric problem). However, 10 years later, when he again has depressed mood and his CD4 count is 100 cells/μl, he may very likely have an OI or a neoplasm affecting his CNS and causing depression (a secondary psychiatric problem).

Table 57-4 Differential Diagnosis of Psychiatric Symptoms in the HIV-Infected Patient

Table 57-5 Neuropsychiatric Side Effects of Highly Active Antiretroviral Therapy and Other Medications Used in the HIV-Infected Patient

* Nucleotide reverse transcriptase inhibitor (NtRTI), related to NRTIs.

† Neuropsychiatric side effects related to plasma level (Gutierrez F, Navarro A, Padilla S, et al: Prediction of neuropsychiatric adverse events associated with long-term efavirenz therapy, using plasma drug level monitoring, Clin Infect Dis 41:1648-1653, 2005).

The diagnostic importance of distinguishing between primary and secondary causes is obvious. Making this differential also has therapeutic implications because results of standard psychiatric treatment for secondary problems may be inferior to those achieved if the problem were primary. As in a patient with traumatic brain injury, stroke, dementia, or advanced age, the brain of a patient with HIV infection can be considered to be sensitive or insulted. Thus, a standard dose of a psychotropic medication may have a more (or less) profound effect in an HIV-infected patient or may cause adverse effects that usually occur only at higher dosages.

Optimum treatment of HIV infection and related conditions is essential for effective psychiatric care. Preferably the patient will be on HAART with agents that penetrate the blood-brain barrier so that the CNS effects of the virus are minimized. When this is not possible (e.g., because of viral resistance patterns), the patient still stands to benefit neuropsychiatrically from HAART because viral suppression and immune restoration will enhance psychiatric treatment. Close collaboration between the psychiatrist and the physician providing the HIV care (usually a specialist in infectious diseases) is crucial.

PSYCHIATRIC DISORDERS

Substance Use Disorders

Substance use disorders are well represented among HIV-infected patients. The 12-month prevalence of drug dependence in the HIV Cost and Services Utilization Study (HCSUS)—a study of a nationally representative sample of nearly 3,000 HIV-infected adults in the United States—was 12.5%.⁹ Between 40% and 45% of injection-drug users in the United States are HIV-positive, and 25% to 30% of non–injection-drug users have the infection.¹⁰ Substance use disorders affect the transmission, course, and treatment of HIV infection in numerous ways (Table 57-6).

Table 57-6 Adverse Effects of Substance Use in the Context of HIV Infection

• Impaired judgment • Disinhibition • Risky sexual practices • Viral transmission • Interactions with psychotropic medications • Poor adherence to antiretroviral therapy • Possible immune suppression

HIV, Human immunodeficiency virus.

So-called “club drugs”—methylenedioxymethamphetamine (MDMA, “ecstasy”), gamma-hydroxybutyrate (GHB, “liquid ecstasy”), and ketamine (“special K”)—and other related compounds (e.g., methamphetamine [speed, crystal meth]) have become increasingly popular drugs of abuse, in part because of their effects on social disinhibition and sexual enhancement. As a result, they can pave the way to HIV transmission. By virtue of pharmacokinetic interactions with the cytochrome P-450 system, the co-administration of “club drugs” with antiretroviral medications can have harmful consequences. Adverse effects of MDMA and GHB, thought to be due to interactions with protease inhibitors, have been reported.^11,12 Protease inhibitors, especially ritonavir, may inhibit the metabolism of amphetamines and ketamine.¹¹

Many stressors during the course of HIV infection threaten both the establishment and the maintenance of sobriety in patients with substance use disorders (Table 57-7). Fortunately, several medications are now available to treat these conditions; unfortunately, some of them are known to have interactions with antiretroviral medications. Interactions between methadone and various antiretroviral agents are presented in Table 57-8. While these interactions may produce measurable changes in methadone plasma levels, such alterations do not consistently result in clinical manifestations.¹³ Withdrawal phenomena have been observed with efavirenz, nevirapine, and nelfinavir.^10,14

Table 57-7 Stressors during HIV Infection

Diagnosis and Treatment

• Testing seropositive • Serial determinations of CD4 count and viral load • Initiation of highly active antiretroviral therapy • Initiation of prophylaxis for opportunistic infections • First hospitalization • Transfer to hospice care

Experience of Symptoms

• Wasting • Diarrheal illness • Treatment-resistant pain and insomnia • Vision-impairing disease (e.g., cytomegalovirus retinitis) • Cognitive and motor dysfunction • Side effects of medications (e.g., fat redistribution syndrome)

Psychosocial Consequences

• Disclosure of HIV serostatus • Disclosure of sexual orientation (e.g., leading to loss of family support) • Loss of employment and health insurance Only gold members can continue reading. Log In or Register to continue Share this: Click to share on Twitter (Opens in new window) Click to share on Facebook (Opens in new window) Related Related posts: 31: Psychiatric Illness during Pregnancy and the Postpartum Period 39: Personality and Personality Disorders 85: The Role of Psychiatrists in the Criminal Justice System 93: International Psychiatry in the Twenty-First Century 27: Drug Addiction 63: Genetics and Psychiatry Stay updated, free articles. Join our Telegram channel Join Tags: Massachusetts General Hospital Comprehensive Clinical Psychiatry Jun 8, 2016 | Posted by admin in PSYCHIATRY | Comments Off on 57: HIV and AIDS Full access? Get Clinical Tree Get Clinical Tree app for offline access Get Clinical Tree app for offline access