Pathology: Hiv/aids

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HIV (Definition)

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HIV = Human Immunodeficiency Virus. Retrovirus isolated and recognized as the etiologic agent of AIDS

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AIDS (Definition)

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AIDS = Acquired Immunodeficiency Syndrome
HIV + Infected Individual + <200 CD4 + T Lymphocytes/mm3
OR
1 of 25 "AIDS defining illnesses"

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Cases of HIV/AIDS Trends
(Exposure Category, Race, Gender, Age)

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Exposure Category - Inc. MSM
Race - Inc. Whites, Asians/Pacific Islanders, American Indians/Alaska Natives
Gender - Inc. Males, Dec. Females
Age - Inc. in Age Groups 15-29, >50

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Transmission

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HIV is not an easily transmitted virus. HIV is spread by DIRECT CONTACT with specific BODY FLUIDS that contain and transmit the HIV virus

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Transmission: Direct Contact

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HIV virus comes in contact with bloodstream, either via an open cut/sore, through a mucous membrane, or direct transfusion

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Transmission: Body Fluids that DO Transmit HIV

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Blood
Seminal Fluid
Vaginal Secretions
Breast Milk

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Transmission: Body Fluids that DO NOT Transmit HIV

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Saliva
Tears
Sweat
Urine
Feces

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Modes of Transmission

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Blood To Blood
Semen and Vaginal Fluid To Blood
Mother to Child

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Risk Factors

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Sexually Transmitted Disease
Using Non-Injectable Drugs

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Occupational Risk

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Patient to Healthcare Worker
Healthcare Worker to Patient

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Postexposure Prophylaxis

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Possible means of decreasing risk of HIV infection
2-3 anti-HIV drugs for short time (4 weeks) after a very recent (<72 hours) unprotected exposure to a person who is HIV+ or HIV status is unknown

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Lifespan of Virus

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HIV is fragile and highly susceptible to physical and chemical agents
Drying of HIV outside the body reduces virus concentration
(cleaning spills 1:10, bleach to water)

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Standard Precautions

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All body secretions and moist membranes and tissues (excluding perspiration) are considered to be potentially infectious and require the use of barriers and/or isolation techniques to prevent transmission of organisms.

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Innate Immune Reaction

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Innate Immune Reaction = Nonspecific response which does not involve "memory" of the foreign substance. Conducted by phagocytic cells, natural killer cells, and cells that release inflammatory mediators.

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Acquired Immune Reaction

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Acquired Immune Reaction - Specific response which does involve "memory" of the foreign substance
-Humoral Immunity
-Cell Mediated Immunity

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Humoral Immunity

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Humoral Immunity = mediated by B-lymphocytes, which produce antibodies. Antibodies recognize and either directly attack antigens or "mark" antigens to then be eliminated by other components of the immune system

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Cell Mediated Immunity

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Mediated by T-lymphocytes (helper,suppressor, cytotoxic), which recognize foreign substances (i.e., all viruses and some bacteria) that hide inside cells where antibodies can't reach them

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Helper (CD4+) T-Lymphocytes

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Secrete cytokines, thereby stimulating other immune system cells (humoral immunity)

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Cytotoxic (CD8+) T-Lymphocytes

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Recognize and kill infected cells

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Suppressor T-Lymphocytes

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Down-regulate the immune response

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The replication cycle of HIV (7)

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1) Virus attaches or binds to host cell (CD4)
2) Virus penetrates the host cell and releases its genomic material
3) Viral RNA is transcribed into viral DNA
4) Viral DNA is integrated into the host cells DNA
5) Transcription and translation of the viral genetic message into viral protein
6) Virus is assembled and released from the host cell
7) Virus undergoes maturation, enabling further HIV replication.

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HIV Effects on the Immune System
-HIV Infects what cells?
- 2 general effects on the immune system

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HIV infects cells with "CD4" surface receptors - helper T-lymphocytes, monocytes, macrophages, dendritic cells
1) Immune System Hyperactiviation
2) Immune System Deficiency

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Immune System Hyperactivation

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-HIV Replication and spread are more efficient in "activated" host cells
-May result in over-stimulation of B-lymphocytes impairing thier ability to make antibodies against other pathogens
-May increase production of cytokines, that may increase HIV replication & have other deleterious effects

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Immune System Deficiency

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HIV disables or destroys host cells --> Increased vulnerability to infection

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Approximate Time Course of HIV Infection

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Primary HIV Infection = 2-7wks
Antibody Test = >4wks
Chronic HIV Infection (No Rx) ~10 yrs
Clinical AIDS = 1-8 years

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Stages of HIV

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Asymptomatic
Early Symptomatic
Advanced Disease (AIDS)

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Primary (Acute) HIV Infection

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4-7 wk period of rapid viral replication following exposure
(fever, malaise, lymphadenopathy, pharyngitis, headache, myalgia, rash)

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Incubation Period

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Time interval between initial HIV infection and the appearance of the first symptom or sign of the disease

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Long-Term Nonprogressors

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Individuals who have been living with HIV for at least 7 years and have stable CD4+ cell counts of >600 cells/mm3 of blood, no HIV related diseases, and no previous antiretroviral therapy

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HIV Related Illnesses (3)

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AIDS Encephalopathy/itis (aka Dementia Complex)
HIV/AIDS Wasting Syndrome
Peripheral Neuropathy

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Opportunistic Infections (definition)

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Infections or cancers that occur especially or exclusively in persons with weak immune systems

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Opportunistic Infections (10)

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Candida Albicans (thrush), Histoplasmosis, Tuberculosis, Pneumocystis Carnii Pneumonia (PCP), Toxoplasma Gondii, Kaposi's Sarcoma, B-Cell Lymphoma (Non-Hodgkins), Herpes Simplex Virus, Cytomegalovirus, Progressive Multifocal Leukoencephalopathy

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Confidential vs. Anonymous Testing

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Confidential = The person provides his or her name and the test result becomes part of thier medical record
Anonymous = The person does not provide his or her name and the test result does not become part of their medical record

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Laboratory Tests (4)

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1) HIV Antibody Testing (EIA, ELISA, Western Blot)
2) HIV Antigen Testing
3) HIV Nucleic Acid Testing (Viral Load Assays)

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HIV Antibody Testing (Detects, conducted on, result time, useful for)

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Detects the presence of antibodies to HIV
Conducted on saliva, urine, and blood
Results can take 20 minutes to 2 weeks
Useful to identify HIV+ persons who would benefit from early medical intervention and HIV negative persons who would benefit from risk reduction counseling

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HIV Antigen Testing (Detects, Useful for)

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Detects presence of HIV viral core p24 protein in the blood
Useful for early deterction of HIV infection

When HIV antibodies become detectable, the p24 antigen is often no longer demonstrable, most likely due to antigen-antibody complexing in the blood.

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HIV Nucleic Acid Testing (Viral Load Assays) (Detects, Useful for, Viral load range)

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Detects presence of HIV RNA in the blood
Useful in predicting risk of HIV disease progression and clinical management
Viral load can range from <200 to >500,000 copies/mL

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CD4+ Cell Count (measurement of, useful for, normal range)

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Measurement of the number of helper T-Lymphocytes (CD4+)
Useful in assessing the status of the immune system
Normal Range: 500-1500/mm3

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Seroconversoin (definition)

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Seroconversion = the development of detectable antibodies to HIV in the blood

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Window Period (definition)

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Window Period = time from infection with HIV until detectable seroconversion

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Newborn Diagnosis (definition)

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Newborn Diagnosis = definitive diagnosis in the newborn is difficult prior to 1 month of age and is usually determined by non-antibody testing.

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Anti-HIV Drugs: Goals (4)

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1) Reduce HIV related morbidity and mortality
2) Improve quality of life
3) Restore and preserve immunologic function
4) Maximally and durably suppress viral load

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Anti-HIV Drugs: Guidelines (2)
(Indications based upon, Treatment offered to)

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1) Indications based upon the presence or absence of symptoms, CD4+ cell count, viral load, and readiness of the patient to begin therapy
2) Treatment should be offered to all patients with <350 CD4+ T-lymphocytes/mm3

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Anti-HIV Drugs: Types (4)

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1) Nucleoside Reverse Transcriptase Inhibitors
2) Non-Nucleoside Reverse Transcriptase Inhibitors
3) Protease Inhibitors
4) Fusion Inhibitors

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HAART

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Highly Active Antiretroviral Therapy
Three or more different drugs.

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Drug Adherence

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Adherence to antiretroviral therapy is critical for durable viral suppression

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Drug resistance

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Reduction in a pathogen's sensitivity to a particular drug.
Thought to result from a genetic mutation

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Prognosis

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Improved morbidity and mortality wiht treatment
Leading cause of death is kidney or liver failure as a result of medical treatment

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Treatment Fundamentals: Treatments should be based on (5)

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Diagnosis, specific problems, indications/contraindications
Patient/Family Goals
Disposition or discharge plan
Mental status and/or patient's personality
Prognosis

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Treatment Spectrum (4)

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Patient/Family Education and Positioning
Therapeutic Exercisre/Functional Mobility
Deficit Specific Rehabilitation
Strength and Endurance Training