HIV/AIDS and Mental Health

 HIV/AIDS and Mental Health

There are no community surveys in Zambia of the prevalence of mental health problems in people with HIV, only personalised estimates from outpatient and in-patient settings. Whether levels of mental health problems are comparable with other medical conditions is also unknown. Similar to other serious illnesses, HIV is associated with a wide range of mental health problems. Organic problems such as delirium are common and are managed in the usual manner; however, a cause may be particularly difficult to find because this is often multifactorial. Specific HIV-related dementias have been described in detail elsewhere (Badkoobehi et al., 2006). Older individuals are at greater risk of HIV-related cognitive impairment and dementia (Becker et al., 2004) and experience more social isolation (Meadows et al., 1998) with improved survival and ageing cohorts, these problems may increase. Gender and associated social consequences contribute to increased risk of mental health problems (Gallego et al., 2000; Hutton and Treisman, 2008). Previous contact with psychiatric services, often because of substance misuse or personality problems, is associated with an increased risk of mental health problems in people with HIV (Gallego et al., 2000).

 

Disease progression and symptomatic disease are associated with a greater risk of psychological morbidity. The risk may be highest at diagnosis, when the manner of communication is important. Another time of increased risk of mental health problems occurs when patients commence antiretroviral medication; with their potential side effects, this time is also associated with major health problems and chronic disabling symptoms (Gallego et al., 2000; Hutton and Treisman, 2008).

 

Health workers in Zambia have for a long time encountered neurologic and psychiatric complications in patients with human immunodeficiency virus (HIV) infection. This is not surprising since the HIV virus enters the central nervous system (CNS) early in the course of the infection. HIV enters the CNS by infecting macrophages and monocytes that then cross the blood brain barrier, carrying the virus with them. Immunohistochemistry studies show that the virus is most densely located in the basal ganglia, subcortical regions, and frontal cortex. The major brain reservoirs for HIV infection and replication are microglia and macrophages. Astrocytes can be infected but are not a site of active HIV replication. Accordingly, HIV-associated neurologic complications are indirect effects of viral neurotoxins (viral proteins gp120 and tat) and neurotoxins released by infected or activated microglia, macrophages, and astrocytes. In the brain, the virus invokes a neurotoxic[1] inflammatory process. These neurotoxic agents create an inflammatory environment by activating uninfected microglia and then proceed to injure surrounding astrocytes and neurons. HIV does not directly infect the neuron, but the neuron is damaged by the effects of various proinflammatory neurotoxins.

HIV infection has so far been linked to:

·       Dementia[1],

·       psychosis,

·       anxiety syndromes,

·       mood disorders ,

·       Suicidality and

·       Alcohol dependence

In addition, other HIV-associated neuropsychiatric complications include the following:

  • Minor cognitive motor disorder, which differs from HAD in severity and degree of functional disability but may progress to HAD.
  • Neurobehavioral impairments (e.g., apathy, depression, anxiety/agitation, sleep disturbance, hypomania).
  • Myelopathy, which is functional disturbance and/or pathologic change to the spinal cord.
  • Aseptic meningitis.

Despite the decreasing incidence of HAD in recent years, cognitive impairment is the most common CNS complication in people with HIV/AIDS. Delirium is the most common cognitive disorder in hospitalized patients with AIDS. The prompt diagnosis of cognitive impairment/dementia and delirium may significantly decrease morbidity and mortality.

 Anxiety Syndromes and HIV/AIDS

As one would expect, studies have shown that, among seropositive individuals, there is a higher rate of that anxiety described by the DSM-IV as Generalized Anxiety Disorder.
In fact studies have also shown that more than 40% of both seronegative and seropositive homosexual men report episodes of clinical anxiety lasting from one to several months, with the majority of onsets being related to seroconversions or commencing after the advent of the AIDS pandemic. In other words, it has been suggested that the very existence of HIV/AIDS is responsible for a significant rise in prevalence rates for clinically diagnosable persistent anxiety. Remarkably, a number of studies have shown that the rates of other major anxiety disorders (panic disorder, obsessive compulsive disorder) do not appear to be markedly above community standards in HIV seropositive individuals, even though HIV can be the manifest content of these conditions. In its clinical dimensions, there is a significant decrease in anxiety reported with both psychotherapy and psychopharmacology.

16.2 Delirium and HIV/AIDS

Delirium is the most common neuropsychiatric complication in hospitalized patients with AIDS. Delirium may be life-threatening and requires immediate medical attention. Occasionally, patients may present with early signs of delirium in the primary care setting. Thus, it is essential that health workers be able to recognize the signs and symptoms and refer patients to the hospital immediately. In these cases, the clinician should then contact the emergency department to follow-up with the disposition of the patient.

The following patients are at risk for developing delirium:

  • Those in advanced stages of immunosuppression.
  • Those with a history of opportunistic infections, substance use, head/brain injuries, or episodes of delirium.
  • Those with HAD or infections and malignancies of the CNS

·        Health workers should assess for delirium when there is a sudden change in a patient’s cognitive functioning, consciousness, or behavior.

·        The hallmarks of delirium are an impairment of consciousness, with a reduced ability to focus or sustain or shift attention, and changes in cognition or development of perceptual disturbances that are not explained by a preexisting dementia. These disturbances may develop over a short period of time, and the symptoms may fluctuate in severity. Delirium is generally a direct physiologic consequence of a medical condition. 

 Management of Patients With HIV Delirium

Treatment of delirium in patients with HIV/AIDS is based on the same principles used for treatment of delirium in patients with other medical illnesses. Correcting the underlying conditions that have led to delirium is the primary treatment. Symptoms such as confusion or agitation can be treated by using low doses of neuroleptics (e.g., haloperidol[1] or risperidone). If symptoms of agitation put the patient or others at risk and are not controlled by low doses of antipsychotics, adding low doses of lorazepam may achieve sedation. Psychiatric consultation may be helpful in management.

 Mood Disorders

 

Rates of major depression are about twice the average for seropositive individuals. It should be noted that this puts HIV/AIDS in the range found for other chronic medical illnesses. In hospitalized HIV patients, as with non-HIV hospitalized patients, rates are much higher and may approach 40%. It is important to note that the somatic and neurologic symptoms may complicate a differential diagnosis in more advanced HIV patients. For them, the clinician should focus for differential diagnosis on saddened mood, distinct loss of pleasure or interest and feelings of worthlessness. Suicidality, especially in patients with advanced AIDS who are not responding to combination therapy, poses a special problem for the clinician. It is recommended that clinician pose herself the question of human dignity versus human life. In any case, suicidality based on a sense of failure or sinfulness should be seen as a diagnostic indicator. Major depression is sometimes accompanied by disturbances of higher cognitive functions, including memory and concentration.  Evidence suggests that such complaints are just as likely to be neurologically based, associated for example with AIDS-related dementia.  Common mental status examinations are relatively insensitive to neurological impairment; health workers should refer patients to experts for neurological testing.  Barring neurological sources, the symptoms of depression respond significantly to both psychotherapy and psychopharmacology.
“Secondary” mania (an organic mood disorder related to some neurological diseases, e.g. meningitis or to pharmacological interventions such as AZT) may appear in HIV illness.  Its treatment is often palliative pharmacology. Otherwise mania does not appear to be appreciably more common for persons with HIV.

 Psychotic Disorders 

 

With the following significant exception, psychotic disorders are not particularly prominent among people with HIV/AIDS.  Full-blown psychosis may appear in late stages of AIDS with a prevalence rate of up to 5%.  Loosening of associations, hallucinations and even elaborate delusions are common.  The diagnosis of such persons is complicated by prominent disturbances of mood.  Moreover, the emergence of psychotic symptoms is prognostic of death within the succeeding year. The fear of this condition, far from universal, but well know in the HIV/AIDS community, is itself a significant source of depression and anxiety. Psychosis associated with HIV infection is more responsive to neuroleptic treatment than to psychotherapy.

AIDS dementia complex (ADC)

This is a metabolic encephalopathy induced by HIV infection and fuelled by immune activation of brain macrophages and microglia (Gray et al., 2000). These cells are actively infected with HIV and secrete neurotoxins of both host and viral origin. The essential features of ADC are disabling cognitive impairment accompanied by motor dysfunction, speech problems and behavioural change. Cognitive impairment is characterised by mental slowness, trouble with memory and poor concentration. Motor symptoms include a loss of fine motor control leading to clumsiness, poor balance and tremors. Behavioural changes may include apathy, lethargy and diminished emotional responses and spontaneity. Histopathologically, it is identified by the infiltration of monocytes and macrophages into the central nervous system (CNS), gliosis, pallor of myelin sheaths, abnormalities of dendritic processes and neuronal loss (Adle-Biassette, et al., 1995; Gray et al., 2000).

AIDS dementia complex (ADC) encompasses cognitive deficits, behavioural changes, and motor involvement. Those affected may manifest deficits in each of the 3 aspects at varying severity. Some may present primarily with cognitive changes such as slowed processing of information captured by neuropsychological testing. Others may present to the psychiatrist for behavioural management. Others may be affected by motor symptoms such as unsteady gait, tremor, or weakness. In 2007, Antinori et al (2007) proposed more refined criteria for diagnosing cognitive impairment associated with HIV. They proposed 3 entities: asymptomatic neurocognitive impairment (ANI), HIV-associated mild neurocognitive disorder (MND), and HIV-associated dementia (HAD). Standardized neuropsychological testing was required to assess the following domains of cognition: language, attention, executive function, memory, speed of information processing, and perceptual and motor skills. In order to make one of the above diagnoses, patients have to have no other etiology of dementia and not have the confounding effect of substance use or psychiatric illness (Antinorri et al., 2007).

The AIDS Dementia Complex is one of the most common and clinically important CNS complications of late HIV-1 infection. It is a source of great morbidity and, when severe, is associated with limited survival. While its pathogenesis remains enigmatic in several important aspects, ADC is generally thought to be caused by HIV-1 itself, rather than to another opportunistic infection (Price, 1998). HIV can cross the blood-brain barrier and enter the central nervous system through virus-infected macrophages. Hence a significant proportion of HIV-infected persons will develop this neurologically based cognitive disorder. For some that will entail subtle impairments in cognitive function (attention deficits, slower processing of information.) Less commonly, and specifically with frank AIDS, some will develop more pronounced cognitive deficits (including linguistic disturbances and psychomotor slowing.) Some patients with this dementia become severely withdrawn and uncommunicative. Occasionally, this dementia progresses to psychosis and delirium.

The dementia associated with HIV can develop over weeks or chronically over years. Symptoms may be similar to those associated with other types of dementia and include decreased short-term memory, decreased attention and concentration; disturbance in word finding, decelerated thought processing, psychomotor retardation (slowed movement), impaired reasoning and intellect, and, in advanced disease, impaired visual-spatial function. Personality changes and mood disturbances such as depression may occur. Less commonly, manic symptoms (agitation, irritability, impulsivity, and excessive talkativeness) and psychosis (hallucinations, delusions, irrational suspiciousness, or paranoia) may be present. Motor deficits are also a part of the HIV-related dementia syndrome and may include muscle weakness, increased or decreased muscle tone, spasticity movements, muscle rigidity or ―cog wheeling, and over or under- reactive reflexes.

 

HIV- Related dementia is treatable. That is, symptoms may be reduced generally with anti-retroviral therapy (ARV). Specific symptoms of the dementia syndrome may be addressed with particular treatments as well. For example, if agitation has developed and is severe, low dose high-potency antipsychotic may be used (e.g. haloperidol 2-5mg po or IM every 4 hours as needed until agitation subsides). Low dose antipsychotic may be used if hallucinations are present as well. Antidepressants are helpful in treating associated depression. Benzodiazepines that are metabolized by the body in a relatively short period (i.e. with short half-lives such as diazepam and lorazepam) may be useful for anxiety and insomnia. However, it is important to be aware that benzodiazepines have also been associated with uninhibited behaviour (i.e. disinhibition) and cognitive impairment and should be used short-term and in the lowest effective doses.

 

CNS infections and tumours

 

Individuals with significant HIV disease may be prone to central nervous system (CNS) infections and tumours that can present with a combination of neurological and psychiatric symptoms. These conditions are outlined in detail below and include neurosyphilis, cryptococcal meningitis, toxoplasmosis, cytomegalovirus (CMV) encephalitis, aseptic meningitis, progressive multifocal leukoencephalopathy (PML), and CNS lymphoma.

 

 

 

Neurosyphilis

 

Syphilis is an infection caused by the spirochete, Treponema pallidum, and has several stages of disease. The primary stage is characterized by enlarged lymph nodes in the groin region and a painless ―chancre or sore that may be located on the genitals. This may disappear without treatment but secondary syphilis characterized by fever, swollen lymph nodes, rash, and genital lesions may appear after approximately 2 years. During this stage syphilitic meningitis with headache, nausea, stiff neck, and occasional cranial nerve deficits may occur. However, more commonly, there are no neurological symptoms but diagnostic tests analyzing spinal fluid may be abnormal. The latent or next phase is also characterized by abnormal diagnostic blood tests and minimal clinical symptoms.

 

The last stage or tertiary phase is when neurosyphilis (syphilis affecting brain tissue) occurs. During this phase other organs including the heart and eyes may be affected as well. Neurosyphilis may present with or with-out symptoms, however diagnostic tests (of spinal fluid) remain abnormal. Syphilis in this stage may cause meningitis or a stroke. There may also be syphilitic dementia associated with seizures, mania, agitation, and grandiose delusional thoughts. Tabes dorsalis (ataxia/loss of balance, lower extremity paresthesia and paresis, hyporeflexia, incontinence, and sharp pains) may occur. ―Gummas or degenerated brain tissue surrounded by thick, fibre-like tissue may, on rare occasion, lead to a space-occupying brain mass.

 

Syphilis may be suspected or detected through tests including VDRL (Venereal Disease Research Laboratory), RPR (rapid plasma reagent), MH-ATP (microhemiagglutination – assay for treponema pallidum), and FTA (fluorescent treponemal antibody). In some instances lumbar puncture may be indicated. Treatment with antibiotics (e.g. penicillin) is effective.

 

Cryptococcal Meningitis

 

Cryptococcus neoformans is a fungus that commonly causes meningitis (swelling of the protective outer-sheath of the brain) in AIDS patients. Symptoms may occur within days or weeks. Early symptoms may be fever, lethargy, persistent, progressive headache; seizure and delirium may occur. Stiff neck typically associated with other types of meningitis is not necessarily present. Some individuals may develop focal neurological symptoms including paralysis of cranial nerves causing blindness and deafness, partial muscle weakness, and over-active reflexes.

 

Treated or untreated, the disease may progress to produce complications including seizure, stroke, swelling of the brain, and coma. Permanent nerve damage and dementia may be long-lasting complications. Cryptococcus is detected usually by analyzing blood and spinal fluid for presence of the fungus. Antifungal antibiotics are used as treatment.

 

Cytomegalovirus (CMV) Encephalitis

 

CMV belongs to the family of Herpes viruses and in addition to neurological disease is associated with disease of the eyes, lungs, oesophagus, intestines, and adrenal gland. Neuropsychiatric manifestations of CMV include primarily encephalitis (global swelling or inflammation of brain tissue). Symptoms associated with encephalitis include fever, headache, lethargy, delirium, dementia, seizure, and coma. Occasionally facial and ocular cranial nerve impairments and weakness of the lower limbs occurs. A definitive diagnosis is made through brain biopsy (analysis of a sample of brain tissue). The recommended treatment is antiviral medication (e.g. intravenous gancyclovir).

 

Aseptic Meningitis

 

A form of meningitis may occur where no pathogen or germ is evident on diagnostic analysis (i.e. no bacteria evident in spinal fluid). This has been referred to as aseptic meningitis. Symptoms may emerge within days to weeks and include headache with or without stiff neck or fever, lethargy and delirium. Rarely impairment of the cranial nerve that controls movements of the facial muscles occurs.  If available, a CT or MRI will indicate inflammation of the tissues that make up a protective sheath enveloping the brain (meninges) and analysis of the spinal fluid will be abnormal.  There is no specific treatment – however the condition may resolve on its own. Supportive measures (e.g. IV fluid), ARV therapy, pain medication, and steroids are used empirically.

 

HIV related dementia

 

The specific symptoms and treatments for depression, anxiety disorders, adjustment disorder, and substance abuse are outlined in previous chapters. Regarding psychiatric medication therapy, drugs that are less likely to interfere with or potentiate the side effects of anti-retroviral medicines should be prescribed.

 

Psychological Issues

 

Fear, uncertainty, anger, and guilt are emotions often experienced by individuals infected by HIV.  Patients may be fearful and uncertain about the effect the virus will have on their bodies and their lives in general. They may fear subsequent medical tests, losing the capacity to function independently, losing the support of friends and family, and death. Providing individuals education and information can reduce fear and uncertainty. For example, directly teaching or referring patients to healthcare providers who can teach them about test procedures, medications and recognizing symptoms of illness early can help individuals feel in greater control of their circumstances. In addition helping patients identify reliable supports (family, friends, clergy, therapist, etc…) can allay fears of abandonment.

 

Anger is common and may be rooted in a sense of unfairness. That is, an individual may feel that he or she has been unduly afflicted. Anger may also stem from a fear of losing control of one‘s life or a fear of social stigma, rejection, or abandonment. It will be important to help the patient understand that having anger is alright and a natural human response. The issue is how the anger is managed. Helping the patient identify and utilize constructive, productive mechanisms for discharging anger is imperative.

 

Guilt is another emotion that is often experienced by individuals infected with HIV. A person with HIV may feel that he or she has brought the virus onto him or herself and should be blamed and punished. Some experience guilt about introducing HIV into the lives of others. They may feel that they have created burden and distress for spouses, partners, parents, children, or friends. Individuals burdened with overwhelming guilt, should be counselled on how to detach negativity and punishment from the virus. Help them understand that, in reality, the virus has nothing to do with punishment. Anyone, ―good or ―bad, has the potential to become infected. In addition, reinforce patients‘self esteem and sense of worth. Having the patients remind themselves of who they are outside of having HIV can bolster self confidence and esteem. Having them recall what people who love them (i.e. family, partners, and friends) like about them can reinforce self esteem.

 

Loss of control

 

As HIV disease progresses, one may need to rely on others to manage activities of daily living such as cooking, cleaning, bathing, dressing, feeding, and administration of medications. A loss of independence and control may be emotionally problematic for individuals who have been accustomed to and taken great pride in providing for themselves. There may be a great effect on self-esteem and self-worth that can lead to anxiety and depression. Help patients control and take responsibility for what they can. If it is clear that one is able to bathe or feed himself or herself, encourage him or her to do so. Reassurance and reinforcement for what they can do may potentially help them to accept and feel less powerless about what they can‘t do. Caregivers often feel helpless because the patient remains ill despite their intervention or support. Caregivers should allow patients to take the lead on expressing what feels like too much or too little help. Those caring for individuals with HIV disease may find it useful to listen without necessarily providing advice to resolve a problem. Attending to non-verbal clues and keeping an open channel of communication could be useful at times.

Essentials of Diagnosis

  1. Marked acquired impairment of at least two ability domains of cognitive function (e.g. memory, attention): typically, the impairment is in multiple domains, especially in learning, information processing and concentration/attention. The cognitive impairment is ascertained by medical history, mental status examination or neuropsychological testing.
  2. Cognitive impairments interfere markedly with day-to-day functioning.
  3. Cognitive impairments are present for at least one month.
  4. Cognitive impairments do not meet the criteria for delirium, or if delirium is present, dementia was diagnosed when delirium was not present.
  5. No evidence of another, pre-existing aetiology that could explain the dementia (e.g. another CNS infection, CNS neoplasm, cerebrovascular disease, pre-existing neurological disease, severe substance abuse compatible with CNS disorder.

 Mortality/Morbidity

ADC causes a significant increase in the overall morbidity due to AIDS.

  • The increase in morbidity results from a combination of factors, including the increased number of hospitalizations, increased duration of hospital stays, and decreased life expectancy compared with AIDS patients who do not have dementia. In the pre-HAART era, AIDS patients who had untreated ADC had an average life span of 6 months, which was significantly less than that for AIDS patients without dementia. This has now increased to 38 months for ADC patients in the Western hemisphere who have been on a stable regimen of HAART (McArthur, 2004).
  • The overall psychosocial and emotional burden on the family and friends of such patients is tremendous, far beyond that of a cognitively intact patient with AIDS.
  • Patients with cognitive difficulties have problems with compliance and adherence to their medication regimen. Because of their neuropsychiatric problems, these patients are likely to be less inhibited and are more prone to HIV-related risk behaviour like unprotected intercourse, and they therefore pose a greater risk of transmission of the virus.  
The goals of Antiretroviral Therapy (ART) are multifaceted and aim to improve the health and quality of life of individuals living with HIV. Here are the primary objectives:

Suppress Viral Load:

Reduce the HIV viral load in the patient's blood to undetectable levels. This helps prevent the progression of HIV to AIDS and reduces the risk of HIV transmission.
Restore and Preserve Immune Function:

Boost and maintain the patient’s immune system by increasing the number of CD4 cells (a type of white blood cell that is crucial for a healthy immune system).
Improve Quality of Life:

Enhance the overall health and well-being of individuals living with HIV, allowing them to lead healthier and more productive lives.
Reduce HIV-related Morbidity and Mortality:

Decrease the incidence of HIV-related complications, illnesses, and deaths by effectively managing the virus.
Prevent HIV Transmission:

Lower the risk of transmitting HIV to others by reducing the viral load to undetectable levels (achieving and maintaining an undetectable viral load means the virus cannot be sexually transmitted, a concept known as U=U, or undetectable equals untransmittable).
Minimize Drug Resistance:

Ensure adherence to the ART regimen to prevent the development of drug-resistant strains of HIV, which can make the virus harder to treat.
Support Adherence and Retention in Care:

Encourage consistent use of ART and regular medical check-ups to ensure the effectiveness of the treatment and to monitor for any potential side effects or complications.

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