Transcript Document

Immune Function
&
HIV
Inflammation

Response of vascular tissues to harmful stimuli




i.e. pathogens, damaged cells, or irritants
Protective attempt by the organism to remove
injurious stimuli and initiate the healing process
May be acute or chronic
Inflammatory response includes :




Vascular response
Cellular response
Formation of exudate
healing
Acute Inflammation

Short term process characterized by the
classic signs of inflammation
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Swelling
Redness
Pain
Heat
Predominant cell
type: neutrophils
Chronic Inflammation




Lasts for weeks – years
Injurious agent persistent
Predominant cell type: lymphocytes and
macrophages
Examples:

Autoimmune reactions
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Rheumatoid arthritis
Prolonged exposure to chemical agents

silica
Immune system structures

The immune system
protects the body from
potentially harmful
substances. The
inflammatory response
(inflammation) is part of
innate immunity. It occurs
when tissues are injured
by bacteria, trauma,
toxins, heat or any other
cause.
Lymphoid Organs


Central lymphoid organs

Thymus
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Bone marrow
Peripheral lymphoid organs
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Tonsils
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Gut-, genital-, bronchial-, &
skin-associated lymphoid tissue

Lymph nodes

spleen
Normal Immune Response

Immunity


State of responsiveness to foreign substances
such as microorganisms and tumor proteins
Types of Immunity

Active Acquired Immunity

Passive Acquired Immunity

Antigen


Large molecules
(usually proteins) on
the surface of cells,
viruses, fungi or
bacteria
Antibody

Protein produced by
the immune system in
response to the
presence of an
antigen

Antigens that get past
the external barriers are
targeted for destruction
by the immune system
Antibodies


Attach to specific antigen
Make it easier for phagocytes to destroy
antigen
Acquired Immunity

Is when the body is exposed to various
antigens and builds a defense that is
specific to that antigen
Passive Immunity

Antibodies that are produced in someone
else's body

Infants have passive immunity because
antibodies are transferred through the
placenta from the mother


Last 6-12 months
Gamma globulin
Given IV, IM
 Temporary protection

Aging and the Immune System

Decline in the immune
system with aging

Characterized by higher
incidence of tumors in
elderly
Also seen with greater
susceptibility to infections
such as influenza and
pneumonia

Altered Immune Response
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
Immunocompetence
 immunity
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Immunodeficiency diseases
Severe infections
Malignancies
 immunity

Hypersensitivity disorders
Allergies
 Autoimmune diseases
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Hypersensitivity Reactions
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Autoimmune Diseases
Four Types
Type 1, II, III are immediate and humoral
 Type IV is a delayed hypersensitivity and cellmediated

Type I Hypersensitivity
Immediate/Anaphylactic Reactions
Occur in in susceptible people
who are highly sensitized to
specific allergens
 Mediated by IgE antibodies
 Release histamine and others by
mast cells and basophils
 Result in systemic inflammatory
response (seconds to minutes)
 Reaction can be local or systemic

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Runny nose anaphylaxis
Mild irritation  sudden death
Type I Hypersensitivity Reactions
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Anaphylaxis
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Immediate release of mediators
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Reaction is within minutes
Can be life threatening
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Injection
Bee sting
Bronchial constriction  airway
obstruction
Vascular collapse
Initial symptoms
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Edema, itching at site of exposure
Can rapidly escalate into shock
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Rapid weak pulse
Hypotension
Dyspnea
cyanosis
See Table 12-12
Anaphylactic Shock
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Most severe type of anaphylaxis
From quick release of mast cells
Estimated 1.3-16.8% of population are “at
risk” for having anaphylactic reaction
especially to insect stings and penicillin
(see table 13-11)
Results in ~1,000 deaths per year

Usually related to sudden cardiovascular
collapse
Anaphylaxis
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IgE acts to release histamine from mast cells
Histamine causes vasodilation of arterioles and
constriction of bronchioles in lungs
(bronchospasm)
Symptoms:
Respiratory distress
Hypotension
Flushed appearance
Anxiety
Unconsciousness
Urticaria (hives)
Angioedema (swelling of lips,
face, throat)
Abdominal pain
Anaphylaxis
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Life-threatening medical emergency d/t
rapid constriction of the airway
Treatment

Epinephrine (adrenaline)
Β-2 adrenergic receptors -> powerful
bronchodilator
 EpiPen
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May also cause tachycardia
Type I Hypersensitivity Reactions
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Atopic reactions

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Inherited tendency to become sensitive to
environmental allergens
Allergic rhinitis (hay fever), asthma,
dermatitis, urticaria
Type II: Cytotoxic and Cytolytic Reactions/
Antibody-Dependent Reactions
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Antibodies produced by the immune system bind to
antigens on pt’s own cell surface
Involve binding of IgG or IgM antibodies to antigens
Antigen-antibody complexes activate the
complement system  reaction/acute inflammation
Mediators of inflammation produce chemicals that
lyse (destroy) cells (erythrocytes, platelets,
leukocytes)
Hours to days
Examples
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Hemolytic transfusion reactions
Goodpasture syndrome
Hashimoto’s thyroiditis
Hemolytic transfusion reactions
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Results from ABO incompatibility
Antibodies coat the foreign erythrocytes
 agglutination  occlusion of blood
vessels
Cellular lysis
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 Acute renal failure
Type III: Immune-Complex Reactions
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Results from antigen-antibody complexes
IgG, IgM complexes are deposited in tissue
(kidneys, joints, lungs, small blood vessels)
 inflammation and cellular destruction
Local or systemic
Hours-days
Associated with systemic lupus
erthymatosus (SLE), rheumatoid arthritis
(RA)
Type IV: Delayed Hypersensitivity
Reactions
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Cell-mediated (not antibody-mediated)
immune response causing tissue damage
Sensitized T lymphocytes attack antigens
and release cytokines which attract
macrophages
2-3 days
Examples:
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Contact dermatitis (poison ivy rash)
Transplant rejection
Allergic Disorders
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Assessment

Health History
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Physical Examination
Diagnostic Studies
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Skin Tests
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Procedure

Results
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Precautions
Chronic Allergies
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Characterized by chronic remissions and
exacerbations
Allergen recognition and control
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Skin testing
Elimination diet
Identification of aggravating factors
Medic Alert bracelet
Collaborative Care
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Epi Pen
Antihistamines
Allergic Disorders (cont.)
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Collaborative Care (cont.)
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Drug Therapy
 Antihistamines
 Sympathomimetic/decongestant drugs
 Corticosteroids
 Antipruritic drugs
 Mast cell-stabilizing drugs (cont.)
Immunotherapy
 Mechanism of action
 Method of administration
Systemic Lupus Erythematosus (SLE)
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Chronic, mulitisystem inflammatory
disease
Typically affects skin, joints, renal,
hematologic, neurologic systems
Etiology: unknown
Autoimmune reactions are directed
against host cells
Clinical manifestations are variable
SLE

Clinical
Manifestations

Dermatological,
M/S,
Cardiopulmonary,
Renal, Nervous
system,
Hematologic,
Infection
susceptibility
Polymysitis & Dermatomyositis
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Diffuse, idiopathic, inflammatory myopathies of
muscle  weakness
Clinical manifestations
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Diagnostic Studies
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Fatigue, weakness
Classic cyanotic heliotrope rash
Joint pain
CK
ESR
Nursing Management
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Assistive
Sjogren Syndrome
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Autoimmune disorder that targets
moisture producing glands  dry mouth,
dry eyes
Usually affects women over the age of 40
“gritty” sensation of eyes
Symptomatic treatment
Immunodeficiency Disorders
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Immune system does not adequately protect
the body
Impairment of 1 or more immune
mechanisms
Primary Immunodeficiency Disorders
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Secondary Immunodeficiency Disorders
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Immune cells are improperly developed/absent
Deficiency based on illness or treatment
Graft-versus-Host Disease
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Transfusion or transplantation with
immunocompetent cells
Immunosuppressive Therapy

Goal: adequately suppress immune response to
prevent rejection while maintaining sufficient
immunity to prevent overwhelming infection
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Calcineurin Inhibitors
Sirolimus
Mycophenolate Mofetil
Polyclonal Antibodies (Antithymocyte Globulin and
Antilymphocyte Globulin)
Monoclonal Antibodies
New Immunosuppressive Therapy
Corticosteroidal Therapy
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AKA “steroids”
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Prednisone
Solu-medrol
Discovered in 1948
Believed to be “miracle cure” for arthritis
Used to relieve the signs, symptoms of
many diseases
Long-term use leads to serious
complications and side effects

Became known as “scaroids”
Corticosteroids

What Are They?


Corticosteroids are drugs closely related to cortisol, a
hormone which is naturally produced in the adrenal
cortex (the outer layer of the adrenal gland).
How Do They Work?

Corticosteroids act on the immune system by blocking
the production of substances that trigger allergic and
inflammatory actions, such as prostaglandins.
However, they also impede the function of white
blood cells which destroy foreign bodies and help keep
the immune system functioning properly. The
interference with white blood cell function yields a side
effect of increased susceptibility to infection.
Corticosteroids

What Conditions Do They Treat?

Corticosteroids are widely used for many conditions.
They are also used to control inflammation of the joints
and organs in diseases such as:
 rheumatoid arthritis
 lupus (systemic lupus erythematosus)
 ankylosing spondylitis
 juvenile arthritis
 inflammatory bowel disease
 polymyositis
 mixed connective tissue disease
 polymyalgia rheumatica
 scleroderma (systemic sclerosis)
 vasculitis
Effects of Corticosteroids
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Anti-inflammatory Action
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 circulating lymphocytes, monocytes and
eosinophils
Inhibit accumulation of leukocytes at site of
inflammation
Inhibit release of substances involved in
inflammatory response
Therefore, suppress manifestations of
inflammation (redness, tenderness, heat,
swelling, local edema)
Effects of Corticosteroids cont’d
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Immunosuppression
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Blood pressure
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Cause atrophy of lymphoid tissue
Suppress cell-mediated immune responses
Decrease production of antibodies
Vasoconstriction
Retention of Na (and water)
Carbohydrate and Protein Metabolism
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Increase hepatic glycogenesis
Increase insulin resistance
Redistribute fat in cushingoid pattern
HIV and AIDS
AIDS in the U.S.

Centers for Disease Control (CDC) estimated that
in 2007 about 1 million people in US are living
with HIV or AIDS

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46% estimated to be men who have sex with men
31% estimated to be adults/adolescents infected through
heterosexual contact
Blacks who make up 13% of population accounted for
almost ½ of the number of HIV/AIDS cases diagnosed
In US and countries where latest therapies are
available, many patients have been managing
their HIV infection with antiretroviral therapy
(ART) for more than 20 years.
AIDS Worldwide

The magnitude of the global HIV/AIDS
epidemic vastly exceeds that in the United
States.
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At the end of 2001, more than 40 million
people were estimated to be living with
HIV/AIDS, and
More than 20 million had already died from
AIDS.
Nearly three quarters of those with the disease
are living in sub-Saharan Africa, where access to
antiretroviral therapy is limited.
HIV and AIDS

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The primary causative agent of AIDS is
HIV
HIV infects lymphocytes and results in
severe immunodeficiency.
Immunodeficiency can lead to infections,
cancers and neurological manifestations.
The HIV Retrovirus
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HIV retrovirus has a particular affinity for
helper T lymphocytes (cells that control
the functions of other immune cells)
Once inside T lymphocytes, HIV produces
abnormal DNA and fuses with the cell’s
normal DNA and takes over the cell’s
machinery.
The invaded lymphocyte then produces
HIV particles
The HIV Retrovirus cont’d
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These viruses exit the dying cell and
repeat the process in other T lymphocytes
Without treatment, T lymphocytes
become depleted as HIV particles increase
The person develops an infection or
malignancy
Transmission of HIV

Major routes of transmission

Through human blood


Sexual Transmission


Including infected needles
Through exchange of semen, vaginal and cervical
fluids
Perinatal Transmission

During pregnancy, labor, delivery or breastfeeding
Disease Development

1.
Typical course of HIV/AIDS is defined by three
phases
Primary infection phase


2.
Chronic asymptomatic/latency phase


3.
Flu-like symptoms
Few days  two weeks
Little or no symptoms of illness
Lasts average of 10 years
Overt AIDS phase

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Occurs when person has a CD4 count < 200 mm3
(normal 800-1000 mm3) or
Development of an AIDS defining illness
Typical Untreated HIV Course
HIV and AIDS

AIDS diagnosed when individual with HIV
develops at least one of the following
Table 14-1):

CD4+T count of less than 200 cells/µl
Healthy adults have CD4+T count >1,000

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Development of opportunistic infection (OI)
Development of opportunistic cancer
Wasting syndrome
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Loss of > 10% of total body mass
Development of dementia
AIDS Defining Illnesses

Opportunistic Infections (OIs)


Develop in people with weakened immune
systems, including people with HIV disease
Most common opportunistic infections are:
Pneumocystis carinii pneumonia (PCP)
 Oropharyngeal or esophageal candidiasis

(thrush)
 Cytomegalovirus (CMV)
 Infections causing diarrhea
AIDS Defining Illnesses cont’d

Neurological disorders


Affect between 40 -60% of all people with
AIDS
Most common: AIDS-related dementia
Mechanism by which HIV infects the central
nervous system is not known
 Characterized by progressive cognitive
dysfunction with motor and behavioral
alterations
 Onset is insidious and follows and unpredictable
course

AIDS Defining Illnesses cont’d

Malignancies


Most frequently seen AIDS-related malignancy
is Kaposi’s Sarcoma (KS)
Tuberculosis
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Leading cause of death from AIDS worldwide
Can affect any body site—usually lungs
Needs to be treated aggressively with drugs
and isolation to prevent its spread to others
Pnuemocystis Pneumonia (PCP)
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Most common opportunistic infection
requiring hospitalization
Caused by pneumocystis jiroveci, formerly
known as pneumocystis carinii
PCP is the indicator condition in 38% of
AIDS pts
Classic triad of symptoms:

Fever, exertional dyspnea, nonproductive
cough
Pneumocystis Pneumonia
Kaposi’s Sarcoma

Once considered rare

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Usually seen in elderly men or organ
transplant patients
In the past 20 years cases have been
associated with HIV infection
With prophylaxis and treatment, the
number of cases d/t to HIV infection has
’d by ~85%
Kaposi’s Sarcoma
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
Typically causes tumors to develop in the tissues
below the skin surface, or mucous membranes
lesions
Lesions typically

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Raised blotches or nodules
Purple, brown or red
Sometimes associated with painful swelling
Skin lesions are disfiguring but not life threatening
Can be life threatening when it involves lungs,
liver or GI tract

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Bleeding
Difficulty breathing
Kaposi’s Sarcoma
Collaborative Care

Monitoring HIV disease progression and
immune function

Initiating and monitoring highly active
antiretroviral therapy (HAART)

Preventing and detecting opportunistic
infections
Collaborative Care

Preventing and treating complications of
therapies

Ongoing health assessment

Baseline data including H&P, immunization
history, psychosocial and dietary evaluation
Collaborative Care

Education about spectrum of HIV,
treatment, preventing transmission,
improving health, and family planning

Repeating and clarification of information
is necessary due to shock and denial
Antiretroviral Therapy (ART)


Rapid development of new drugs, combinations
Since the introduction of ART survival with AIDS
has improved dramatically


From an average of 3.1 years to >13 years
New recommendations are to start antiretroviral
therapy later than previously thought

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Drug resistance
Medication side effects
Uncertain benefit
Antiretroviral Therapy


In the US alone, ART has saved an
estimated total of at least 3 millions years
of life.
ART associated with clinically important
adverse reactions
Antiretroviral Therapy
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Side effects are considerable
Most common and serious s/e include
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Diabetes
Cardiovascular disease
Cytopenias
Pancreatitis
Peripheral neuropathy
Hypersensitivity (rash, fever, risk of death)
Hepatitis
GI toxicity (diarrhea and nausea)
Antiretroviral Therapy


Different drug groups used to treat HIV
Work at different points along the replication
cycle
1.
2.
3.
4.

Nucleoside reverse transcriptase inhibitors (NRTIs)
Non-nucleoside reverse transcriptase inhibitors
(NNRTIs)
Protease Inhibitors
Fusion Inhibitors
Most critical, modifiable factor affecting success:
patient adherence to drug regimen
Nucleoside reverse transcriptase
inhibitors (NRTIs)


Block reverse transcriptase, a protein HIV
needs in order to replicate
As NRTIs were introduced and used in
combination


survival increased
Increase in drug related complications
Nausea
 Vomiting
 Painful neuropathies
 Life-threatening pancreatitis

NRTIs
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Combivir
Emtriva
Epivir
Epixicom
Hivid
Retrovir
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Trizivir
Truvada
Videx EC
Viread
Zerit
Ziagen
Protease inhibitors (PIs)

Block protease

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Protein needed for HIV replication
Introduced December, 1995
Approved for use in combination with
NRTIs
PIs
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Agenerase
Aptivus
Crixivan
Fortovase
Invirase
Keletra
Lexiva

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Norvir
Prezista
Reyataz
viracept
Antiretroviral drugs
Drug Class
Agent
Common Side
Effects
Nucleoside reverse
transcriptase inhibitors
(NRTI)
Zidovudine (AZT, ZDV)
Didansosine (ddI)
Anemia, netropenia,
Non-nucleoside reverse
transcriptase inhibitors
(NNRTIs)
Nevirapine (brand name:
Viramune)
Efavirenz, also known as
EFV (brand name: Sustiva)
Hepatitis, rash
Protease inhibitors
Saquinavir (brand name:
Invirase)
Indinavir (brand name:
Crixivan)
GI intolerance,
thrombocytopenia
hyperglycemia, lipid
abnormalities
Highly Active Antiretroviral Therapy
(HAART)

HAART is a treatment regimen that combines 3
antiretroviral drugs

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
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Widespread use of PIs in 1996, successful
treatment of HIV infection extended life by
decades
HAART also associated with problems

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
2 from NRTI class
1 from PI class
Poor oral bioavailability
High pill burden
Intolerable adverse reactions
Long-term toxicities
Most of these problems have been minimized
Chronic challenges


Because HAART has significantly reduced
mortality, HIV is now considered a chronic,
manageable illness
Patients and their families must face difficulties of
any chronic illness

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Medication toxicities
Exacerbation of mental health issues
Complex medication regimens
Lifestyle adjustments
Lipid and Glucose abnormalities
Dyslipidemia



Most patients with HIV infected patients
who aren’t on HAART have lipid
abnormalities
PIs are most often associated with
dyslipidemia
Can lead to accelerated atherosclerosis
Insulin Resistance



~25% of population has insulin resistance
In patients receiving PI therapy, insulin
resistance 60-85%
Insulin resistance usually appears 10 – 20
years before type 2 diabetes
Patient Teaching

Encourage your patient to:



Exercise
Control his/her weight
Reduce cardiovascular risk
Quit smoking
 Use low-dose aspirin therapy
 Manage lipids
 Maintain BP within normal limits
 Monitoring for diabetes

Independent Nursing Interventions

1.
2.
3.
Most important interventions for
reducing cardiovascular risk:
Teaching patients about smoking
cessation
Encouraging exercise
Optimal weight control
Smoking & HIV

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Prevalence of adult smokers in US ~21%
In HIV population ~72%
In HIV-infected I.V. drug users ~96%
Besides contributing to C-V disease, smoking is
major contributor to:

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


Bacterial pneumonia
Abdominal aortic aneurysms
Cataracts
Periodontal disease
Cancers of lung, stomach, uterus, pancreas, kidney
Smoking and HIV


When nurses advise and encourage hospital
patients who smoke to quit, 15% - 20% of
them quit, compared with 3% who don’t
receive counseling at all.
4 A’s of smoking cessation counseling:




Ask about his smoking
Advise him to quit smoking
Assist him with quitting by providing educational
materials, or referral for pharmacologic aids
Arrange follow-up to discuss progress toward
smoking cessation
Other HIV/AIDS drugs
Drug/Drug Class
Agent
Common Side
Effects
Antiviral
(Herpes virus)
Acyclovir
GI intolerance,
renal toxicity
Antifungal
(cryptococcal fungus)
Amphotericin B
Bad reaction when
the drug is given
Renal problems.
Antiviral
(Kaposi’s Sarcoma)
Alpha Interferon
CNS and flu-like
reactions
Nsg Diagnosis: Alteration in comfort:
nausea


Alteration in comfort: nausea related to
medications, opportunistic infections
Goal: stable/ideal weight


Appropriate nutritional intake
Interventions:





Avoid hot, spicy or greasy food
BRAT diet (bananas, rice, applesauce, toast)
Eat dry food (crackers, toast, dry cereal)
Sip cold, carbonated beverages (ginger ale) or
try peppermint, chamomile or ginger tea
Antiemetics as ordered
Nsg Diagnosis: Alteration in Skin
Integrity: Rash



Alteration in Skin Integrity: Rash r/t
medications (especially NNRTIs)
Goal: skin intact
Interventions




Natural skin moisturizer (aloe)
Antihistamines (benadryl) for mild rash
Antihistamine Corticosteroid (prednisone) as
ordered for severe rash
Avoid harsh soaps and perfumes
Nsg Diagnosis: Potential for Impaired
Gas Exchange


Alteration in tissue perfusion r/t anemia, d/t
disease process, medications (especially AZT)
Goal:



Hgb/Hct within acceptable range
Acceptable pO2 without supplemental O2
Interventions





Administration of erythopoietin (Epogen) as ordered
O2 as ordered
Blood products as ordered
Teach to rest between periods of activity
 HOB during episodes of dyspnea
Nsg Diagnosis: Potential for Injury/
Infection


Potential for Infection r/t disease or
treatment
Goal:



No signs/symptoms of active infection
WBC maintained within acceptable range
Interventions





“Compromised Host Precautions”: private room, etc.
Good handwashing by all visitors and personnel
VS q 2 hours
Minimize invasive procedures
Avoid raw fruits, vegetables and milk products
That’s all folks….
Study and do well!!…