HIV – AIDS

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DEFINITION

  • Human immunodeficiency virus (HIV) infection is an infection by one of two viruses that progressively destroys white blood cells called lymphocytes, causing acquired immunodeficiency syndrome (AIDS) and other diseases that result from the impaired immunity

Types

  • HIV-1
    • Most common in the Western Hemisphere, Europe, Asia, and in Central, South, and East Africa
  • HIV-2
    • Most common in West Africa, although HIV-1 also exists

Retrovirus

  • A type of virus that stores genetic information as RNA rather than as DNA
  • When the virus enters a targeted host cell, it releases its RNA and an enzyme (reverse transcriptase), and then makes DNA using the viral RNA as a pattern
  • The viral DNA then is incorporated into the host cell DNA
  • Each time a host cell divides, it also makes a new copy of the integrated viral DNA along with its own genes
  • The viral DNA can take over the functions of the cell (become activated), causing the cell to produce new virus particles
  • These new viruses are released from the infected cell to invade other cells

History

  • In the early 1980s, epidemiologists (people who study the factors that affect the frequency and distribution of diseases) recognized a sudden increase in two conditions among American homosexual men
    • One was Kaposi’s sarcoma, a rare cancer
    • The other was pneumocystis pneumonia, a form of pneumonia that occurs only in people with a compromised immune system
    • The failure of the immune system that allowed the growth of rare cancers and the development of rare infections came to be known as AIDS
      • Immune system failure was found also in injecting drug users, hemophiliacs, and recipients of blood transfusions as well as in bisexual men
      • Some time later, the syndrome began to occur in heterosexuals who weren’t drug users, hemophiliacs, or recipients of blood transfusions

PATHOGENESIS

  • Gradual decline of the body’s immune system, primarily through the disabling of CD4+ cells
  • In order to establish infection in a person, the virus must enter cells such as lymphocytes, a type of white blood cell
  • The genetic material of the virus is incorporated into the DNA of an infected cell
  • The virus reproduces itself inside the cell, eventually destroying the cell and releasing new virus particles.
  • The new virus particles then infect other lymphocytes and can destroy them as well
  • Because HIV infection destroys helper T lymphocytes, it weakens the body’s system for protecting itself from infection and cancer
  • People infected with HIV lose helper T lymphocytes (CD4+ cells) in three phases over months or years
    • A healthy person has a CD4+ lymphocyte count of roughly 800 to 1,300 cells per microliter of blood
    • In the first few months after HIV infection, this count may decrease by 40 to 50 percent
    • After about 6 months, the number of virus particles in the blood reaches a steady level, which varies from person to person
      • Many years may pass during which the HIV-infected person has a slowly declining, below-normal count of CD4+ lymphocytes
    • In the 1 to 2 years before recognizable AIDS develops, the count of CD4+ lymphocytes usually drops more rapidly
      • The person’s vulnerability to infection increases as the CD4+ lymphocyte count falls below 200 cells per microliter of blood
  • HIV infection also disrupts the function of B lymphocytes, the part of the immune system that produces antibodies, often causing them to produce excess antibodies
    • These antibodies are directed mainly against HIV itself and those infections with which the person had previous contact
    • But the antibodies are not very helpful against many of the opportunistic infections of AIDS
    • At the same time, destruction of CD4+ lymphocytes by the virus reduces the immune system’s ability to recognize new invaders and target them for attack

PREVALENCE

  • 34.3 million worldwide are infected with HIV (according to United Nations Programme on HIV/AIDS & World Health Organization, 2000)
  • Since its beginning, almost 19 million have died from AIDS
  • Sub-Saharan African countries are the most profoundly impacted
    • Up to one quarter of young adults being HIV seropositive
  • In US (1999 numbers)
    • 850,000 are living with HIV/AIDS
    • 430,000 have died from it

CENTERS FOR DISEASE CONTROL (CDC) CLASSIFICATION SYSTEM

Two Factors

  • History of Clinical Conditions
    • Category A: Patients who have remained medically asymptomatic or have had only a transient illness at seroconversion or persisting hymphadenopathy
    • Category B: Patients with more serious HIV-related conditions (minor opportunistic infections)
    • Category C: Patients who have had more serious AIDS-defining illnesses such as Pneumocystis carinii pneumonia
  • Degree of Immunosuppression (based on CD4+ T-lymphocyte cell count per microliter of blood)
    • Category 1 (the healthiest): CD4 counts of greater than 500
    • Category 2: CD4 cell counts from 200-499
    • Category 3: CD4 counts below 200
  • AIDS is diagnosed in those with CD4<200 and /or a category C complication

SYMPTOMS

  • Some people develop symptoms similar to those of infectious mononucleosis a few weeks after first contracting HIV infection
  • A fever, rashes, swollen lymph nodes, and general discomfort can last 3 to 14 days
  • Most symptoms then disappear, although the lymph nodes may stay enlarged
  • Additional symptoms may not appear for years.
  • However, large amounts of the virus circulate in the blood and other body fluids immediately, so a person becomes contagious soon after becoming infected
  • Within several months of contracting HIV, people may repeatedly experience mild symptoms that don’t yet fit the definition of full-blown AIDS.
  • A person may have symptoms of HIV infection for years before developing the distinctive infections or tumors that define AIDS
    • These symptoms include swollen lymph nodes, weight loss, a fever that comes and goes, an unwell feeling, fatigue, recurring diarrhea, anemia, and thrush (fungal infection of the mouth)
    • Weight loss (wasting) is a particularly troublesome problem
  • By definition, AIDS begins with a low CD4+ lymphocyte count (less than 200 cells per microliter of blood) or the development of opportunistic infections (infections by organisms that don’t cause disease in people with a healthy immune system)
    • Cancers such as Kaposi’s sarcoma and non-Hodgkin’s lymphoma may also develop
    • Both the HIV infection itself and the opportunistic infections and cancers produce the symptoms of AIDS
    • However, only a few people with AIDS die from the direct effects of HIV infection.
    • Usually, death is caused by the cumulative effects of many opportunistic infections or tumors.
    • Organisms and diseases that normally pose little threat to healthy people can rapidly lead to death in those with AIDS, especially when the CD4+ lymphocyte count drops below 50 cells per microliter of blood

Common Opportunistic Infections

  • Thrush
    • Often one of the first infections to appear
  • Vaginal Yeast Infections
    • Often one of the earliest symptom of HIV infection in a woman
    • May be frequent that aren’t easily cured.
    • However, recurring vaginal yeast infections are commonly seen in otherwise healthy women and may be caused by other factors, such as oral contraceptives, antibiotics, and hormonal changes
  • Cryptococcal Meningitis
    • Results from infection with Cryptococcus neoformans (a yeast)
    • Characterized by headaches, altered mentation, fever, and nausea
  • Pneumocystis Carinii
    • Pneumonia caused by this fungus is a common
    • Often one of the first serious opportunistic infection to develop
    • It was the most common cause of death among HIV-infected people before methods to treat and prevent the pneumonia were improved
  • Toxoplasmosis
    • The most common cause of mass lesions in AIDS patients
    • Usually results in multifocal abscesses in both hemispheres, particularly in the basal ganglia
    • Characterized by a fever, altered mentation, seizures, and focal signs that develop in a few days
    • When it reactivates in patients with AIDS, Toxoplasma causes severe infection primarily in the brain.
  • Tuberculosis
    • More frequent and more deadly in people who have HIV infection and is difficult to treat if the strains of the tuberculosis bacterium are resistant to several antibiotics
  • Mycobacterium Avium Complex
    • A common cause of fever, weight loss, and diarrhea in people with advanced disease
    • It can be both treated and prevented with recently developed drugs.
  • Cryptosporidium
    • Gastrointestinal infection that is also common with AIDS
    • It is a parasite that may be acquired from contaminated food or water, causes severe diarrhea, abdominal pain, and weight loss
  • Progressive Multifocal Leukoencephalopathy (PML)
    • A viral infection of the brain
    • A demyelinating disorder
    • Usually occurs in subcortical regions, but occasionally may affect the gray matter
    • Lesions do not produce a mass effect
    • The first symptoms are usually a loss of strength in an arm or leg and loss of coordination or balance
    • Within days or weeks, the person may be unable to walk and stand, and death usually occurs within a few months
  • Cytomegalovirus (CMV) Encephalitis
    • Highly endemic in American homosexual men (95%)
    • Became a common, uncontrolled problem in advanced AIDS before the advent of HAART
    • There appear to be a distinct dementia associated with CMV-E
    • People with AIDS are also highly susceptible to many other bacterial, fungal, and viral infections
  • Common Tumors
    • Kaposi’s Sarcoma: A tumor that appears as painless, red to purple, raised patches on the skin, affects people with AIDS, especially homosexual men
    • Lymphomas: Tumors of the immune system which may first appear in the brain or other internal organs
      • Typically, patients present with slowly progressive neurological deterioration and may die within 3 months
      • Focal lesions may develop
      • Difficult to differentiate lymphomas from toxoplasmosis
    • Women are prone to developing cancers of the cervix
    • Homosexual men are prone to developing cancer of the rectum

CENTRAL NERVOUS SYSTEM INVOLVEMENT

  • HIV enters the CNS early in the course of the disease
  • A small subset of individuals may develop severe dementia as the initial manifestation of AIDS, but it is primarily a late stage phenomenon
  • Milder forms of cognitive sequelae are more common
  • 50-66% of AIDS patients may develop some form of CNS disease as a result of the direct or indirect effects of HIV
  • It does not appear that HIV directly infects neurons
  • It is hypothesized that damage to neurons may be mediated my macrophages and microglia
  • The presence of HIV may lead to chronic activation of macrophages/micrglia, which can result in increased prodection of cytokines such as IL-1, IL-6, and TNF-alpha by these cells
    • These cytokines may then damage neuronal structures directly or set off disturbances in other cells (e.g., astroglia) that are important in maintaining the viability of neurons
  • Neuroimaging shows abnormalities frequently seen as atrophy, white matter lesions, and abnormal metabolism
  • HIV is predominantly found in the subcortical brain regions
  • However, neocortical regions are also affected by HIV

NEUROCOGNITIVE SEQUELAE

  • Neurocognitive complications can be classified as being primary or secondary
    • Primary complications are linked directly to HIV infection of the brain
    • Secondary complications are linked to immunodeficiency or other adverse events associated with HIV disease or its treatment
      • Delirium is a common secondary complication (well covered in the book)
  • Grant and Atkinson (1995) Taxonomy
    • Neurocognitive deficit: One cognitive area is impaired
    • Neurocognitive impairment: Deficits in at least two domains
    • Neurocognitive disorder: Impairment is “clinically meaningful”; definite symptoms such as problems at work or difficulties with other aspects of social or day-to-day functioning
  • Grant and Atkinson (1995) Diagnostic Schema
    • Mild Neurocognitive Disorder/Minor Cognitive Motor Disorder MND/MCMD (coincides with neurocognitive impairment)
      • Characterized by difficulty in concentrating, unusual fatigability, subjectively slowed down, and mild memory problems
      • May by seen as anxiety, depression, or hypchondriasis
      • Cognitive testing reveals difficulties with information processing speed, divided attention, sustained effortful processing, deficiencies in learning and recalling new information
      • Problem solving, abstract reasoning, and motor speed are occasionally seen
      • Verbal skills are less affected (although may have slower fluency)
    • HIV-Associated Dementia [HAD] (coincides with neurocognitive disorder)
      • Characterized by severe impairments in cognitive functioning with marked interference in social occupational performance
      • Impairments commonly see in learning and recall, psychomotor speed, fluency, and executive functioning
      • Affective lability, irritability, withdrawal, apathy, or inappropriateness may be present
      • As dementia advances, delirium is often present
      • Ataxia, weakness, and incoordination can be prominent
      • Decreased survival rate
      • Dementia in AIDS patients is strongly correlated with a decrease survival time
      • Occurs almost exclusively in more advanced AIDS patients
  • Sidtis and Price (1997) AIDS Dementia Complex (ADC) Staging Scheme
    • Stages
      • Stage 0 (normal): Normal mental and motor function
      • Stage 0.5 (equivocal/subclinical): Either minimal or equivocal symptoms of cognitive or motor dysfunction characteristic of ADC or mild signs, but without impairment of work or capacity to perform ADLs (e.g., may show slowed extremity movement); Gait and strength are normal
      • Stage 1 (mild): Unequivocal evidence of functional, intellectual, or motor impairment characteristic of ADC, but able to perform all but the more demanding aspects of work or ADL; Can walk without assistance
      • Stage 2 (moderate): Cannot work or maintain the more demanding aspects of daily life, but able to perform basic activities of self-care; Ambulatory but may require a single prop
      • Stage 3 (severe): Major intellectual incapacity or motor disability
        • Cannot follow news or personal events
        • Cannot sustain complex conversation
        • Considerable slowing of all output
        • Cannot walk unassisted, requiring walker or personal support, usually with slowing and clumsiness of arms as well
      • Stage 4 (end stage): Nearly vegetative
        • Intellectual and social comprehension and responses are at a rudimentary level
        • Nearly or absolutely mute
        • Paraparetic or paraplegic with double incontinence
    • At the early stages, we see complaints of lapses in concentration, increased difficulty in performing tasks that were once routine, forgetfulness, difficulty walking, diminished legibility in writing, loss of interest in daily activities, and social withdrawal
    • We do not see an initial amnestic state
    • Progresses to a final stage that is nearly vegetative, with only rudimentary intellectual function

PSYCHOSOCIAL FACTORS

  • Quality of life changes (driving skills may or may not be affected)
  • Medication management is significant (if cognition is deficient, may not be able to management own medications)
  • Work functioning decreases
  • Increased substance abuse (either as a risk factor or subsequent to the diagnosis) – may also impact cognitive functioning
  • Stigmatism
    • Threat of loss of employment
    • Threat of denial of medical benefits and or life insurance
    • May affect immediate social support

NEUROPSYCHIATRIC DISORDERS

  • Adjustment Disorders
  • Anxiety Disorders: GAD, Panic D/O, OCD
  • Mood Disorders: Depression, Mania (i.e., Bipolar)
  • Psychosis
    • May or may not be pre-existing
    • People with Schizophrenia are at a higher risk for contracting HIV
    • Brief Reactive Psychosis, Depression with Psychotic Features, Psychoactive Substance Use Disorders, and organic sources
  • Substance Use Disorders
    • May or may not be pre-existing

PROGNOSIS

  • Exposure to HIV doesn’t always lead to infection, and some people who have been repeatedly exposed over years remain uninfected
  • Moreover, many infected people have remained well for over a decade
  • Without benefit of current drug treatments, a person infected with HIV had a 1 to 2 percent chance of developing AIDS in the first several years after infection
    • The chance continued at about 5 percent each year thereafter
    • The risk of developing AIDS within 10 to 11 years of contracting the infection was about 50 percent
  • An estimated 95 to 100 percent of infected people will eventually develop AIDS, but the long-term effects of newly developed drugs used in combination may improve this outlook
  • The first drugs used to treat HIV, such as AZT (zidovudine) and ddI (didanosine), have reduced the numbers of opportunistic infections and increased the life expectancy of people with AIDS, and combinations of these drugs produce even better results
  • Newer nucleoside drugs, such as d4T (stavudine) and 3TC (lamivudine), and HIV protease inhibitors, such as saquinavir, ritonavir, and indinavir, are even more potent
  • In some, combination therapy reduces the amount of virus in the blood to undetectable levels. Cures, however, have not been proven
  • With the development of new antiviral drugs and improved methods to treat and prevent opportunistic infections, many people retain their physical and mental abilities for years after the diagnosis of AIDS